Regulatable and modulable background expression control in prokaryotic synthetic circuits by auxiliary repressor binding sites.

Expression control in synthetic genetic circuitry, for example, for construction of sensitive biosensors, is hampered by the lack of DNA parts that maintain ultralow background yet achieve high output upon signal integration by the cells. Here, we demonstrate how placement of auxiliary transcription factor binding sites within a regulatable promoter context can yield an important gain in signal-to-noise output ratios from prokaryotic biosensor circuits. As a proof of principle, we use the arsenite-responsive ArsR repressor protein from Escherichia coli and its cognate operator. Additional ArsR operators placed downstream of its target promoter can act as a transcription roadblock in a distance-dependent manner and reduce background expression of downstream-placed reporter genes. We show that the transcription roadblock functions both in cognate and heterologous promoter contexts. Secondary ArsR operators placed upstream of their promoter can also improve signal-to-noise output while maintaining effector dependency. Importantly, background control can be released through the addition of micromolar concentrations of arsenite. The ArsR-operator system thus provides a flexible system for additional gene expression control, which, given the extreme sensitivity to micrograms per liter effector concentrations, could be applicable in more general contexts.

SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites

The Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their association with the co-repressor Silencing Mediator Of Retinoic And Thyroid Hormone Receptors (SMRT). We found that, while HDAC5 and HDAC4 mutants lacking their N-terminal phosphorylation sites (HDAC4(MUT), HDAC5(MUT)) are constitutively nuclear, co-expression with SMRT renders them exportable by signals that trigger SMRT export, such as synaptic activity, HDAC inhibition, and Brain Derived Neurotrophic Factor (BDNF) signaling. We found that SMRT's repression domain 3 (RD3) is critical for co-shuttling of HDAC5(MUT), consistent with the role for this domain in Class IIa HDAC association. In the context of BDNF signaling, we found that HDAC5(WT), which was more cytoplasmic than HDAC5(MUT), accumulated in the nucleus after BDNF treatment. However, co-expression of SMRT blocked BDNF-induced HDAC5(WT) import in a RD3-dependent manner. In effect, SMRT-mediated HDAC5(WT) export was opposing the BDNF-induced HDAC5 nuclear accumulation observed in SMRT's absence. Thus, SMRT's presence may render Class IIa HDACs exportable by a wider range of signals than those which simply

Inscripció ibèrica, grafits i marques amfòriques prodecents de la Fogonussa (Sant Martí de Maldà, Riucorb, Urgell)

[cat] Es donen a conèixer diversos objectes singulars localitzats en superfície en els jaciments ibèric i romà de la Fogonussa, que romanien inèdits en la població de Sant Martí de Maldà, municipi de Sant Martí de Riucorb. La selecció està formada per una vora d'àmfora grecoitàlica tardana, que conté una inscripció ibèrica, dues nanses de vasos contenidors ibèrics amb grafits i tres nanses d'àmfora ibèrica estampillades, una d'elles amb la figura d'un griu.

Rakennukset ja rakentajat Raision Ihalassa rautakauden lopulla ja varhaisella keskiajalla

Turun yliopiston arkeologian oppiaine tutki Raision Ihalan historiallisella kylätontilla, ns. Mullin eduspellolla, asuinpaikan, josta löydettiin maamme oloissa harvinaisen hyvin säilyneitä rakennusten puuosien jäännöksiä. Löytö on ainutlaatuinen Suomen oloissa ja sillä on kansainvälistäkin merkitystä, koska hyvin säilyneet myöhemmän rautakauden ja varhaisen keskiajan maaseutuasuinpaikat, joista tavataan puujäännöksiä, ovat harvinaisia erityisesti itäisen Itämeren piirissä. Rakennukset on ennallistettu käyttäen tiukkaa paikallisen analogian (’Tight Local Analogy’) metodia, erityisesti suoraa historiallista analogista lähestymistapaa. Tätä tarkoitusta varten muodostettiin aluksi arkeologinen, historiallinen ja etnografinen lähdemalli. Tämä valittiin maantieteellisesti ja ajallisesti relevantista tutkimusaineistosta pohjoisen Itämeren piiristä. Tiedot lounaisen Suomen rakennuksista ja rakennusteknologiasta katsottiin olevan tärkein osa mallia johtuen historiallisesta ja spatiaalisesta jatkuvuudesta. Lähdemalli yhdistettiin sitten Mullin arkeologiseen aineistoon ja analyysin tuloksena saatiin rakennusten ennallistukset. Mullista on voitu ennallistaa ainakin kuusi eri rakennusta neljässä eri rakennuspaikassa. Rakennusteknologia perustui kattoa kannattaviin horisontaalisiin pitkiin seinähirsiin, jotka oli nurkissa yhdistetty joko salvoksella tai varhopatsaalla. Kaikissa rakennuksissa ulkoseinän pituus oli 5 – 7 metriä. Löydettiin lisäksi savi- ja puulattioita sekä kaksi tulisijaa, savikupoliuuni ja avoin liesi. Runsaan palaneen saven perusteella on mahdollista päätellä, että katto oli mitä todennäköisimmin kaksilappeinen vuoliaiskatto, joka oli katettu puulla ja/tai turpeella. Kaikki rakennukset olivat samaa tyyppiä ja ne käsittivät isomman huoneen ja kapean eteisen. Kaikki analysoitu puu oli mäntyä. Ulkoalueelta tavattiin lisäksi tunkioita, ojia, aitoja ja erilaisia varastokuoppia. Rakennukset on ajoitettu 900-luvun lopulta 1200-luvun lopulle (cal AD). Lopuksi tutkittiin rakennuksia yhteisöllisessä ympäristössään, niiden ajallista asemaa sekä asukkaiden erilaisia spatiaalisia kokemuksia ja yhteyksiä. Raision Ihalaa analysoidaan sosiaalisen identiteetin ja sen materiaalisten ilmenemismuotojen kautta. Nämä sosiaaliset identiteetit muodostuvat kommunikaatioverkostoista eri spatiaalisilla ja yhteisöllisillä ta¬soilla. Näitä eri tasoja ovat: 1) kotitalous arjen toimintoineen, perhe ja sukulaisuussuhteet traditioineen; 2) paikallinen identiteetti, rakennus, rakennuspaikka, asuinpaikan ympäristö ja sen käyttö, (maa)talo ja kylä; 3) Raision Ihalan kylä laajemmassa alueellisessa kontekstissaan pohjoisen Itämeren piirissä: kauppiaiden ja käsityöläisten kontaktiverkostot, uskonnollinen identiteetti ja sen muutokset.

El territorio y la ciudad de Tarraco

This paper presents a brief description of the archaeological research in the territory and in the city of Tarraco, the ancient capital of provincia Hispania Tarraconensis and one of the main centres for the spread of Hispanic Christianity. Althoug Tarraco was the last capital under imperial control and the firs Hispanic metropolitan see, the city had only a secondary role by comparison with other Hispanic cities during late antiquity. This evolution shaped the development of Tarraco during the 7th century, but archaeologists identify an important architectural vitality still in the 6th century at the same time as other episcopal cities were evolving. During this period, the final Christianization of the symbolic spaces of ancient paganism took place, establishing the ideological basis of medieval urbanism that is still preserved today. The paper also interprets the sites through raising key questions as well as describing rural settlements, where archaeological knowledge is not so far advanced, due in part to the difficult nature of archaeological research, and in part to the need to study new construcitve models, as well as to the systematic collection of the relevant material culture.

Archaeological Excavation Confirms the Geophysical Anomalies Recorded at the Cathedral of Tarragona - A Comparative Study

An integrated geophysical survey was conducted in September 2007 at the Cathedral of Tarragona (Catalonia, NE Spain), to search for archaeological remains of the Roman temple dedicated to the Emperor Augustus. Many hypotheses about its location have been put forward, the most recent ones suggesting it could be inside the present cathedral. Tarragona’s Cathedral, one of the most famous churches in Spain (12th century), was built during the evolution from the Romanesque to Gothic styles. As its area is rather wide, direct digging to detect hidden structures would be expensive and also interfere with religious services. Consequently, the use of detailed non-invasive analyses was preferred. A project including Electrical resistivity tomography (ERT) and Ground probing radar (GPR) was planned for a year and conducted during a week of intensive field survey. Both ERT and GPR provided detailed information about subsoil structures. Different ERT techniques and arrays were used, ranging from standard Wenner-Schlumberger 2D sections to full 3D electrical imaging using the MYG array. Electrical resistivity data were recorded extensively, making available many thousands of apparent resistivity points to obtain a complete 3D image after full inversion. The geophysical results were clear enough to persuade the archaeologists to excavate the area. The excavation confirmed the geophysical interpretation. In conclusion, the significant buried structures revealed by geophysical methods under the cathedral were confirmed by recent archaeological digging as the basement of the impressive Roman Temple that headed the Provincial Forum of Tarraco, seat of the Concilium of Hispania Citerior Province.

Understanding Neolithic Southern Levant: case studies of archaeological semiosis in action

I undersökningen tillämpas Charles Sanders Peirces semiotik för en kritisk granskning av arkeologiska tolkningsprocesser. Enligt Peirce bygger all betydelsegivning på tecken, som kan vara teckningar, föremål, ord, byggkonstruktioner eller egentligen vad som helst. Ett tecken är tredimensionellt: ”objekt”, ”tecken” och ”tolkning”. I sina tidiga skrifter definierar han tre grundtyper för tecknet, Index, Icon och Symbol. De grundläggande definitionerna i Peirces semiotik blir till ett slags lins. När den placeras på skrifter av en arkeolog som uttolkar tecken, framträder deras inre uppbyggnad, motiveringar och logiska konsekvens klart. Att beakta är, att denna bok är lika lite avsedd att utgöra en systematisk klarläggning av den arkeologiska semiotiken, som en omfattande beskrivning av symboliken i det neolitiska Mellanöstern. Analysen är deskriptiv och inte avsedd att utvärdera tolkningarnas riktighet, utan enbart att klarlägga hur arkeologen kommit fram till dessa. Som objekt har valts neolitiska södra Levanten, där viktiga fynd gällande denna i mänsklighetens kulturhistoria så betydelsefulla skede har gjorts. Förhistorien är intressant med tanke på arkeologisk semiosis, eftersom uttolkaren av en symbol inte kan stöda sig på textfynd, utan måste på annat sätt upptäcka vad ett föremål eller en byggnad betytt för sin upphovsman. Att upptäcka en trovärdig betydelse är ofta en mycket svår och understundom rentav omöjlig uppgift. Efter att förhållandet mellan semiotik och arkeologi dryftats analyseras i boken John Garstangs och Kathleen M. Kenyons grundläggande tolkningar i Jeriko, Denise-Schmandt Besserats jämförande analyser för uttolkningen av \'Ain Ghazalis kranium, Michele A. Millers kontextuella analys i Jarmuk samt David Lewis-Williams’ starkt strukturalistiska analys av betydelsen av fynden i \'Ain Ghazal. Peirces semiotik har använts som stöd för arkeologin i mycket mindre utsträckning än F. de Saussures lingvistiska ja strukturalistiska semiotik. I Mellanöstern har man hittills inte alls gjort det. Ingen av de forskare som behandlas i boken hänvisar själv till semiotik eller tecken. Logiken i uttolkningen av dessa undersökningar är mycket invecklad, och de av Peirce gestaltade processerna för betydelsegivning visar sig härvidlag utgöra en ytterst klargörande kritisk apparat.

The potential of social networking sites in inpatriate adjustment

People make up one of the most important resources for a corporation and therefore it has to continuously seek an ever more diverse and international workforce. Inpatriation is another way of utilizing foreign expertise in a corporation. An inpatriate refers to a person that is on an international assignment at the headquarters of a corporation, where they have been sent either from a subsidiary abroad or from a third country outside the corporation. Strengthening the social network of the inpatriate and their family contributes to the adjustment process and furthermore the success of the work assignment. As social networking sites are currently the fastest developing personal networking tools in the world, it is interesting to see how they can help in inpatriate adjustment. The objective of this thesis is to explore the potential of social networking sites (SNS) in inpatriate adjustment. The main objective can be divided into three sub objectives: 1. What is SNS used for during the inpatriate assignment? 2. What are the inpatriates’ motivations to use SNS? 3. Could the three facets of adjustment (work, interaction and general) be gained through SNS? This qualitative study utilizes the theme interview data collection method and the thematic analysis approach for analysing the interview data. From the interviews with five Indian inpatriates in Finland the most mentioned uses of SNS were related to participating (sharing opinions, recommendations and discussing things and connecting to friends, family and colleagues) and consuming (collecting information for work and free time), the least mentioned use of SNS was producing (posting videos, photos and updates). An interesting finding was that the five interviewees did not use SNS for purely entertainment motives at all during their assignment. This thesis found that all three facets of adjustment could potentially be gained through SNS.

Mapping the sites of latency and reactivation by bovine herpesvirus 5 (BoHV-5) and a thymidine kinase-deleted BoHV-5 in lambs

A thymidine kinase (tk)-deleted bovine herpesvirus 5 (BoHV-5tkΔ) was previously shown to establish latent infection and reactivate - even poorly - in a sheep model (Cadore et al. 2013). As TK-negative alphaherpesviruses are unlike to reactivate in neural tissue, this study investigated the sites of latency and reactivation by this recombinant in lambs. For this, groups of lambs were inoculated intranasally with the parental BoHV-5 strain (SV-507/99) or with the recombinant BoHV-5tkΔ. During latent infection (40 days post-inoculation, pi), the distribution of recombinant virus DNA in neural and non-neural tissues was similar to that of the parental virus. Parental and recombinant virus DNA was consistently detected by PCR in trigeminal ganglia (TGs); frequently in palatine and pharyngeal tonsils and, less frequently in the retropharyngeal lymph nodes. In addition, latent DNA of both viruses was detected in several areas of the brain. After dexamethasone (Dx) administration (day 40pi), the recombinant virus was barely detected in nasal secretions contrasting with marked shedding of the parental virus. In tissues of lambs euthanized at day 3 post-Dx treatment (pDx), reverse-transcription-PCR (RT-PCR) for a late viral mRNA (glycoprotein D gene) demonstrated reactivation of parental virus in neural (TGs) and lymphoid tissues (tonsils, lymph node). In contrast, recombinant virus mRNA was detected only in lymphoid tissues. These results demonstrate that BoHV-5 and the recombinant BoHV-5tkΔ do establish latent infection in neural and non-neural sites. Reactivation of the recombinant BoHV-5tkΔ, however, appeared to occur only in non-neural sites. In anyway, the ability of a tk-deleted strain to reactivate latent infection deserves attention in the context of vaccine safety.