Choosing the optimal spectroscopic toolkit to understand protein function

Spectroscopy was one of the earliest methods used to study the properties and reactions of proteins, and remains one of the most powerful and widely used approaches to this day. A sometimes bewildering range of spectroscopies is now available, applicable to different sample states, timescales and indeed biological questions. This editorial describes some of the most relevant spectroscopic methods together with a selection of illustrative examples.</jats:p

Examining the effects of sodium ions on the binding of antagonists to dopamine D2 and D3 receptors

Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo

Consuming post-disaster destinations: The case of Sichuan, China

Addressing the call for a better understanding of tourist behavior in relation to post-disaster destinations, this study explores the motivations and intentions of potential domestic tourists (from non-hit areas) to visit Sichuan, China in the aftermath of an earthquake. Drawing on dark tourism theories, this study offers a more comprehensive insight into the consumption of post-disaster destinations, aiming to capture the impact of the changes to the destination’s attributes on tourist behavior. The findings move beyond the common approach to tourism recovery, which solely focuses on reviving the traditional ‘‘non-dark’’ products. This study reveals the importance of newly formed dark attributes that emerge from the disaster as another means to destination recovery, reflected in the emergence of new tourist segments

Twisting in the Wind: Monumental Weathervanes in Classical Antiquity

Monumental weathervanes have been overlooked as a tiny but important genre of ancient bronze sculpture. This is the first collective study of all three definite examples: the so-called ‘triton’ on the Tower of the Winds in Athens, a copy of this somewhere in Rome, and the winged female ‘Anemodoulion’ on the Bronze Tetrapylon in Constantinople. I propose to identify the intended subjects of these sculptures as the weather-deities Aiolos and Iris, thereby restoring a part of each monument’s original meaning that was unknown to the authors of our ancient written accounts. I also suggest that monumental weathervanes were first invented in Hellenistic Alexandria, which may explain why the Tower of the Winds shared the octagonal design of the Pharos, and why the Anemodoulion was mounted upon a bronze pyramidion

A study on the specificity of the association between hippocampal volume and delayed primacy performance in cognitively intact elderly individuals.

Delayed recall at the primacy position (first few items on a list) has been shown to predict cognitive decline in cognitively intact elderly participants, with poorer delayed primacy performance associated with more pronounced generalized cognitive decline during follow-up. We have previously suggested that this association is due to delayed primacy performance indexing memory consolidation, which in turn is thought to depend upon hippocampal function. Here, we test the hypothesis that hippocampal size is associated with delayed primacy performance in cognitively intact elderly individuals. Data were analyzed from a group (N=81) of cognitively intact participants, aged 60 or above. Serial position performance was measured with the Buschke selective reminding test (BSRT). Hippocampal size was automatically measured via MRI, and unbiased voxel-based analyses were also conducted to explore further regional specificity of memory performance. We conducted regression analyses of hippocampus volumes on serial position performance; other predictors included age, family history of Alzheimer's disease (AD), APOE ε4 status, education, and total intracranial volume. Our results collectively suggest that there is a preferential association between hippocampal volume and delayed primacy performance. These findings are consistent with the hypothesis that delayed primacy consolidation is associated with hippocampal size, and shed light on the relationship between delayed primacy performance and generalized cognitive decline in cognitively intact individuals, suggesting that delayed primacy consolidation may serve as a sensitive marker of hippocampal health in these individuals

New Investigations in the Environment, History and Archaeology of the Iraqi Hilly Flanks: Shahrizor Survey Project 2009-2011

Recent palaeoenvironmental, historical, and archaeological investigations, primarily consisting of site reconnaissance, in the Shahrizor region within the province of Sulaymaniyah in Iraqi Kurdistan are bringing to light new information on the region’s social and socio-ecological development. This paper summarises two seasons of work by researchers from German, British, Dutch, and Iraqi-Kurdish institutions working in the survey region. Palaeoenvironmental data have determined that during the Pleistocene many terraces developed which came to be occupied by a number of the larger tell sites in the Holocene. In the sedimentary record, climatic and anthropogenic patterns are noticeable, and alluviation has affected the recovery of archaeological remains through site burial in places. Historical data show the Shahrizor shifting between periods of independence, either occupied by one regional state or several smaller entities, and periods that saw the plain’s incorporation within large empires, often in a border position. New archaeological investigations have provided insight into the importance of the region as a transit centre between Western Iran and northern and southern Mesopotamia, with clear material culture links recovered. Variations between periods’ settlement patterns and occupations are also beginning to emerge

The Pathology of EMT in Mouse Mammary Tumorigenesis

Epithelial-mesenchymal-transition (EMT) tumorigenesis in the mouse was first described over 100 years ago using various terms such as carcinosarcoma and without any comprehension of the underlying mechanisms. Such tumors have been considered artifacts of transplantation and of tissue culture. Recently, EMT tumors have been recognized in mammary glands of genetically engineered mice. This review provides a historical perspective leading to the current status in the context of some of the key molecular biology. The biology of mouse mammary EMT tumorigenesis is discussed with comparisons to human breast cancer

Reading Abdallāh b. Abdallāh al-Tarjumān’s Tuḥfa (1420) in the Ottoman Empire: Muslim-Christian Polemics and Intertextuality in the Age of “Confessionalization”

In 1604, a charismatic Sufi sheikh from Tunis commissioned the translation into Ottoman Turkish of Abdallāh b. Abdallāh al-Tarjumān’s polemical text entitled Tuḥfat al-Adīb fī alradd ʿalā ahl al-ṣalīb (1420), with the intention of presenting it to Ottoman Sultan Ahmed I. Soon after, this text became one of the most widely known and disseminated anti-Christian polemical texts in the Islamic world, and by the late ninteenth century, in Europe as well. The article examines the circumstances of Tuḥfa’s translation from Arabic into Ottoman Turkish, the actors involved, the narrative’s trajectory from Tunis to Istanbul, its reception by the Ottoman reading public, as well as impact on the development of an Ottoman polemical genre of self-narrative of conversion to Islam. Transcription and translation of such an Ottoman narrative, which appears to have been directly influenced by Tuḥfa, is featured in the article’s appendix. By focusing on the trajectory of a single text belonging to the genre of religious polemics, the article bridges the traditionally disconnected academic discussions pertaining to the early modern Iberian, North African and Ottoman history and demonstrates their inherent connectivity in the age of confessional polarization (16th-17th centuries).<br><br>En 1604, un carismático sufí de Túnez encargó la traducción al turco otomano del texto de polémica titulado Tuḥfat al-Adīb fī al-radd ʿalā ahl al-ṣalīb (1420) de Abdallāh b. Abdallāh al-Tarjumān, con la intención de presentárselo al Sultán otomano Ahmed I. Poco después, este texto se convirtió en uno de los textos de polémica anti-Cristiana mejor conocidos y leídos en el mundo islámico y en Europa, a finales del siglo XIX. Este artículo estudia las circunstancias en que se realizó la traducción de la Tuḥfa del árabe al turco otomano, los actores involucrados en esa traducción, la narrativa de su trayectoria desde Túnez hasta Estambul, su recepción por el público letrado otomano y, finalmente, su impacto en el desarrollo del género de polémica otomana en las narrativas de conversión al Islam. En el apéndice de este artículo se incluye una transcripción y traducción de esa narrativa, que parece estar directamente influida por la Tuḥfa. Mediante el estudio de la trayectoria de un único texto perteneciente al género de la polémica religiosa, este artículo evita las discusiones académicas, tradicionalmente desconectadas entre sí porque estudian la historia moderna ibérica, norte africana y otomana de forma separada, demostrando así su íntima conexión en la época de polarización confesional (ss. XVI y XVII)

Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients

BACKGROUND: Though the dysfunction of central dopaminergic system has been proposed, the etiology or pathogenesis of schizophrenia is still uncertain partly due to limited accessibility to dopamine receptor. The purpose of this study was to define whether or not the easily accessible dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia. RESULTS: 44 drug-medicated schizophrenics for more than 3 years, 28 drug-free schizophrenics for more than 3 months, 15 drug-naïve schizophrenic patients, and 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of D3 and D5 dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors was compared in each group. After taking antipsychotics in drug-free and drug-naïve patients, the dopamine receptors of peripheral lymphocytes were sequentially studied 2nd week and 8th week after medication. In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes significantly increased compared to that of controls and drug-medicated schizophrenics, and D5 dopamine receptor mRNA expression increased compared to that of drug-medicated schizophrenics. After taking antipsychotics, mRNA of dopamine receptors peaked at 2(nd) week, after which it decreases but the level was above baseline one at 8(th) week. Drug-free and drug-naïve patients were divided into two groups according to dopamine receptor expression before medications, and the group of patients with increased dopamine receptor expression had more severe psychiatric symptoms. CONCLUSIONS: These results reveal that the molecular biologically-determined dopamine receptors of peripheral lymphocytes are reactive, and that increased expression of dopamine receptor in peripheral lymphocyte has possible clinical significance for subgrouping of schizophrenis