Differential crosstalk between estrogen receptor (ER) alpha and ER beta and the thyroid hormone receptor isoforms results in flexible regulation of the consensus ERE

Crosstalk between nuclear receptors is important for conversion of external and internal stimuli to a physiologically meaningful response by cells. Previous studies from this laboratory have demonstrated crosstalk between the estrogen (ER) and thyroid hormone receptors (TR) on two estrogen responsive physiological promoters, the preproenkephalin and oxytocin receptor gene promoter. Since ERa and ERb are isoforms possessing overlapping and distinct transactivation properties, we hypothesized that the interaction of ERa and b with the various TR isoforms would not be equivalent. To explore this hypothesis, the consensus estrogen response element (ERE)derived from the Xenopus vitellogenin gene is used to investigate the differences in interaction between ERa and b isoforms and the different TR isoforms in fibroblast cells. Both the ER isoforms transactivate from the consensus ERE, though ERa transactivates to a greater extent than ERb. Although neither of the TRb isoforms have an effect on ERa transactivation from the consensus ERE, the liganded TRa1 inhibits the ERa transactivation from the consensus ERE. In contrast, the liganded TRa1 facilitates ERb-mediated transactivation. The crosstalk between the TRb isoforms with the ERa isoform, on the consensus ERE, is different from that with the ERb isoform. The use of a TRa1 mutant, which is unable to bind DNA, abolishes the ability of the TRa1 isoform to interact with either of the ER isoforms. These differences in nuclear receptor crosstalk reveal an important functional difference between isoforms, which provides a novel mechanism for neuroendocrine integration.

Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells

Thyroid hormones (T) and estrogens (E) are nuclear receptor ligands with at least two molecular mechanisms of action: (i) relatively slow genomic effects, such as the regulation of transcription by cognate T receptors (TR) and E receptors (ER); and (ii) relatively rapid nongenomic effects, such as kinase activation and calcium release initiated at the membrane by putative membrane receptors. Genomic and nongenomic effects were thought to be disparate and independent. However, in a previous study using a two-pulse paradigm in neuroblastoma cells, we showed that E acting at the membrane could potentiate transcription from an E-driven reporter gene in the nucleus. Because both T and E can have important effects on mood and cognition, it is possible that the two hormones can act synergistically. In this study, we demonstrate that early actions of T via TRalpha1 and TRbeta1 can potentiate E-mediated transcription (genomic effects) from a consensus E response element (ERE)-driven reporter gene in transiently transfected neuroblastoma cells. Such potentiation was reduced by inhibition of mitogen-activated protein kinase. Using phosphomutants of ERalpha, we also show that probable mitogen-activated protein kinase phosphorylation sites on the ERalpha, the serines at position 167 and 118, are important in TRbeta1-mediated potentiation of ERalpha-induced transactivation. We suggest that crosstalk between T and E includes potential interactions through both nuclear and membrane-initiated molecular mechanisms of hormone signaling.

Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

Opinion dynamics of learning agents: does seeking consensus lead to disagreement?

We study opinion dynamics in a population of interacting adaptive agents voting on a set of issues represented by vectors. We consider agents who can classify issues into one of two categories and can arrive at their opinions using an adaptive algorithm. Adaptation comes from learning and the information for the learning process comes from interacting with other neighboring agents and trying to change the internal state in order to concur with their opinions. The change in the internal state is driven by the information contained in the issue and in the opinion of the other agent. We present results in a simple yet rich context where each agent uses a Boolean perceptron to state their opinion. If the update occurs with information asynchronously exchanged among pairs of agents, then the typical case, if the number of issues is kept small, is the evolution into a society torn by the emergence of factions with extreme opposite beliefs. This occurs even when seeking consensus with agents with opposite opinions. If the number of issues is large, the dynamics becomes trapped, the society does not evolve into factions and a distribution of moderate opinions is observed. The synchronous case is technically simpler and is studied by formulating the problem in terms of differential equations that describe the evolution of order parameters that measure the consensus between pairs of agents. We show that for a large number of issues and unidirectional information flow, global consensus is a fixed point; however, the approach to this consensus is glassy for large societies.

Interaction and Persuasion:An analysis of the use of rhetorical devices in Gordon Brown's speech to the Labour Party Conference, on September 25, 2006

This essay has identified and analysed rhetorical devices in Gordon Brown’s speech delivered at the Labour Party conference on September 25, 2006. The aim of the study was to identify specific rhetorical devices which are described as interactional resources, analyse their uses and discuss possible effects that they may have when included in a political speech. The results are based on my own interpretations but are supported by information provided in current literature by analysts and researchers of rhetoric use. The result findings could probably serve as evidence of the need for better understanding of the devices used by politicians in their relentless endeavours to influence audience decisions.

Creating Prestige and Global Networks through Conference Rituals

An international conference is a secular ritual which serves to create, recreate and shape global-wide translocal cultural sharings. Social anthropological theories and methods are used to show that, besides being an information flow junction, the international conference is a network crossroad and a way of socialising new members into aninternational research community. It is also capable of creating prestige and honour for the individual researcher,for the arranging research team, university and city. Rituals do not merely reflect the social relations or cosmology of a society, but are events that in themselves do important things through ritual forms and symbolic statements.

Report on IEA Task-14 activities on solar collector systems conference in Rome, 25-29 Jan. 1993

The memebers of IEA (International Energy Agency) Task 14 (Advaced Active Solar Systems) met in Rome during January 1993. The latest developments in several countries were presented and discussed during this meeting. This report describes briefly the recent work carried out on small scale systems in the Domestic Hot Water (DHW) working group of Task 14, as reported by the representatives from Canada, Denmark, Germany, Holland and Switzerland. Klaus Lorenz, SERC, attended the meeting as observer and presented our work on small-tube heat exchangers. Several participants expressed their interest. A summary of his presentation is included in this report.

Rapport från 20th European Photovoltaic Solar Energy Conference and Exhibition : Barcelona 6-10 juni 2005

På uppdrag av STEM bevakade Eva Lindberg från Centrum för solenergi-forskning, SERC, Högskolan Dalarna, 20th European Photovoltaic Solar Energy Conference and Exhibition, Barcelona, 6-10 juni 2005. Ca 1700 personer fanns på deltagarlistan. På grund av konferensen omfattning kan endast ett litet urval av föredrag och utställare kommenteras i rapporten. Konferensprogrammet var indelat på följande områden:1. Grundläggande fakta, nya komponenter och material2. Kristallina kiselsolceller and materialteknologi3. Amorft och mikrokristallint kisel4. CIS, CdTe och andra (II-VI) ternära tunnfilmsceller5. PV-moduler och komponenter i PV-system6. PV-system i nätanslutna applikationer7. Globala aspekter på PV-solelektricitet8. PV-industrins resultatFoU om kristallina solceller dominerade stort, sedan tunnfilmsceller av främst amorft kisel. Intressant var att återvinning är föremål för FoU; dels återvinning av kiselsolceller när panelen tjänat ut; dels återvinning av Cu, Cd, Se och Te när tunnfilmscellerna tas ur bruk.237 företag fanns representerade i utställningen, varav 20 från Kina. Tyskland dominerade stort. Utställningen teman var följande: 1) Tillverkare av kiselplattor, solceller, PV-moduler, koncentratorer, solföljare (se bild nedan) 2) Tillverkare och återförsäljare av utrustning och material 3) Integrering och distribution av system 4) Mätningar och kontrollteknologi 5) Forskning och laboratorier 6) Service, teknik, konsulting 7) Myndigheter och föreningar 8) Media och förlag 9) Tillverkare av inverterare 10) Övrigt.