Identification of the Amino Acid Subsets Accounting for the Ligand Binding Specificity of a Glutamate Receptor

AbstractIn a situation so far unique among neurotransmitter receptors, glutamate receptors share amino acid sequence similarities with the bacterial periplasmic binding proteins (PBPs). On the basis of the primary structure similarity of two bacterial periplasmic proteins (lysine/arginine/ornithine- and phosphate-binding proteins) with the chick cerebellar kainate-binding protein (KBP), a member of the ionotropic glutamate receptor family, we have generated a three-dimensional model structure of the KBP extracellular domain. By an interplay between homology modeling and site-directed mutagenesis, we have investigated the kainate binding properties of 55 different mutants (corresponding to 43 positions) and studied the interactions of some of these mutants with various glutamatergic ligands. As a result, we present here the subsets of amino acids accounting for the binding free energies and specificities of KBP for kainate, glutamate, and CNQX and propose a three-dimensional model, at the microarchitectural level, of the glutamatergic binding domain

Venom biotechnology: casting light on nature’s deadliest weapons using synthetic biology

Venoms are complex chemical arsenals that have evolved independently many times in the animal kingdom. Venoms have attracted the interest of researchers because they are an important innovation that has contributed greatly to the evolutionary success of many animals, and their medical relevance offers significant potential for drug discovery. During the last decade, venom research has been revolutionized by the application of systems biology, giving rise to a novel field known as venomics. More recently, biotechnology has also made an increasing impact in this field. Its methods provide the means to disentangle and study venom systems across all levels of biological organization and, given their tremendous impact on the life sciences, these pivotal tools greatly facilitate the coherent understanding of venom system organization, development, biochemistry, and therapeutic activity. Even so, we lack a comprehensive overview of major advances achieved by applying biotechnology to venom systems. This review therefore considers the methods, insights, and potential future developments of biotechnological applications in the field of venom research. We follow the levels of biological organization and structure, starting with the methods used to study the genomic blueprint and genetic machinery of venoms, followed gene products and their functional phenotypes. We argue that biotechnology can answer some of the most urgent questions in venom research, particularly when multiple approaches are combined together, and with other venomics technologies

The Early Royal Society and Visual Culture

Recent studies have fruitfully examined the intersection between early modern science and visual culture by elucidating the functions of images in shaping and disseminating scientific knowledge. Given its rich archival sources, it is possible to extend this line of research in the case of the Royal Society to an examination of attitudes towards images as artefacts –manufactured objects worth commissioning, collecting and studying. Drawing on existing scholarship and material from the Royal Society Archives, I discuss Fellows’ interests in prints, drawings, varnishes, colorants, images made out of unusual materials, and methods of identifying the painter from a painting. Knowledge of production processes of images was important to members of the Royal Society, not only as connoisseurs and collectors, but also as those interested in a Baconian mastery of material processes, including a “history of trades”. Their antiquarian interests led to discussion of painters’ styles, and they gradually developed a visual memorial to an institution through portraits and other visual records.AH/M001938/1 (AHRC

"Men pris och läge går före" : Konsumentens värderingar kring hållbarhet och dess relation till konsumentens beteende vid hotellbokning

Världen står inför stora utmaningar i framtiden sett till hur vi överanvänder de resurser som jorden har att erbjuda. Jordens miljö och dess hållbarhet är allt vi människor har och så som Bruntlandrapporten beskriver det måste vi agera nu för att bevara den för våra framtida generationer (WCED, 1987). Samtidigt ökar medvetenheten kring klimatförändringarna som vårt agerande har lett fram till. I och med det ställs allt större krav dels på individer men även på företag att ta sitt ansvar för klimatet och jorden.  För företagen har det blivit alltmer vanligt att arbeta med CSR (Corporate Social Responsibility) som är ett verktyg för att integrera miljöansvaret, det sociala ansvaret samt det ekonomiska ansvaret i företagets verksamhet. Det privata resandet ökar allt mer och därmed även behovet av hotellboende. Hotellboendet är det gästen konsumerar och då detta är en upplevelse som inte fysiskt går att ta med sig hem benämns hotellbranschen som en del av tjänsteindustrin. Tjänster är komplexa och det finns utmaningar som hotellen därmed ställs inför då det blir mycket svårare att förmedla rätt information till gästerna innan gästen anländer till hotellet, vad är egentligen det de köper? Vi vill i denna studie sammanfoga hotellens hållbarhetsarbete med komplexiteten kring att hotell ingår i tjänsteindustrin och få en förståelse för vilka värderingar konsumenter har kring hållbarhet generellt och hur dessa värderingar relaterar till beteendet gällande bokning av hotell i synnerhet. Vidare undrar vi vad som skulle kunna motivera gäster att välja mer miljövänliga boendealternativ och hur, utifrån gästens värderingar, hotellen bör positionera sig. Detta undersöker vi genom att utföra en kvalitativ studie genom fokusgrupper och med en deduktiv forskningsansats i och med att vi utgår från tidigare forskning och teorier. Deltagarna i vår studie uppger att det för dem är ovanligt att relatera hotellbokning med hållbarhet men att det är intressant för dem att väcka dessa tankebanor. Resultatet visar också att de anser att hotellen har ett stort ansvar att vara miljömedvetna och hållbara men när det kommer till dem själva har vissa deltagare svårt att ta sitt ansvar fullt ut då hållbarhetsdebatten anses för ny för dem medan andra deltagare hävdar att det är rätt att tvingas göra aktiva val som väcker tankar hos individen om hur en kan påverka sin omvärld. Med det sagt så tyder resultatet av studien på att deltagarna har miljövänliga värderingar men att dessa värderingar inte alltid implementeras i beteendet, detta på grund av att vårt agerande baserad på vårt egna behov snarare än vad som är bra för hela världen. Deltagarna framhäver dock att i dagsläget så är det alltid pris och läge som kommer först när det gäller viktiga faktorer vid hotellbokning. Vi ser också tendenser i fokusgruppernas diskussioner som vi tolkar som att för att ett hotells arbete inom hållbarhet ska fungera behöver fyra faktorer uppfyllas. Arbetet skall vara Givande för gästen, Trovärdigt, Påtagligt och Utbildande.The world faces great challenges in the future due to how we overuse the resources of the earth. The environment of the earth and its sustainability is all that we as humans have and as the Bruntland report describes, it is important to act now in order to preserve the earth for future generations (WCED, 1987). At the same time, the awareness of climate change is increasing and with that, the impact that our actions have had so far on the climate. With that being said, a greater demand for responsibility is being called for, both for individuals and corporate businesses. For businesses it has become more normal to work with a tool called CSR, Corporate Social Responsibility, which integrates the environmental, social and economic responsibilities for the business and its activities. The private travelling increases more and more and with that also the need for staying at hotels. The stay at the hotel is what the guest consumes and because the stay is an experience that you physically cannot bring home with you, the hotel trade is a part of the service sector. Services are complex and there are challenges for the hotels in conveying the right information to the guest before he or she arrives to the hotel and letting them know what it actually is that they buy and pay for. In this study, we want to merge the hotels sustainability work with the complexity of being a service company. We also want to gain an understanding of which values consumers have regarding sustainability in general and how these values relate to the behavior when booking a hotel particularly. Further on, we wonder what could motivate guests to choose more environmentally friendly hotel options, and from the guest’s values, how hotels should position themselves. We investigate this by performing a qualitative study by using focus groups with a deductive approach, meaning that we base our work on previous studies and theories and uses them to draw conclusions of the result. The participants in our study declare that it is unusual to relate hotel booking with sustainability but at the same time they think that it is interesting to awake this way of thinking. The results also shows that the participants think that the hotels have a great responsibility in being sustainable but when they are to apply this on themselves, some participants struggle a bit more and meaning that the debate of sustainability is too young for them. In the other hand, several other participants think that it is right to be forced into making own decisions that raise awareness about how individuals can influence the world around themselves. With that being said, the result of the study points towards that the participants have environmentally values but that these values not always is being implemented in their behavior, probably because that we base our behavior on our own needs rather than what is good for the whole world. The participants point out that price and location always comes first when booking a hotel. Lastly, we see tendencies in the discussions in the focus groups which we interpret into four factors which hotels need to fulfill in order to conduct functional sustainability actions. The actions should be Awarding for the guest, Trustworthy, Tangible and Educational

"Men pris och läge går före" : Konsumentens värderingar kring hållbarhet och dess relation till konsumentens beteende vid hotellbokning

Världen står inför stora utmaningar i framtiden sett till hur vi överanvänder de resurser som jorden har att erbjuda. Jordens miljö och dess hållbarhet är allt vi människor har och så som Bruntlandrapporten beskriver det måste vi agera nu för att bevara den för våra framtida generationer (WCED, 1987). Samtidigt ökar medvetenheten kring klimatförändringarna som vårt agerande har lett fram till. I och med det ställs allt större krav dels på individer men även på företag att ta sitt ansvar för klimatet och jorden.  För företagen har det blivit alltmer vanligt att arbeta med CSR (Corporate Social Responsibility) som är ett verktyg för att integrera miljöansvaret, det sociala ansvaret samt det ekonomiska ansvaret i företagets verksamhet. Det privata resandet ökar allt mer och därmed även behovet av hotellboende. Hotellboendet är det gästen konsumerar och då detta är en upplevelse som inte fysiskt går att ta med sig hem benämns hotellbranschen som en del av tjänsteindustrin. Tjänster är komplexa och det finns utmaningar som hotellen därmed ställs inför då det blir mycket svårare att förmedla rätt information till gästerna innan gästen anländer till hotellet, vad är egentligen det de köper? Vi vill i denna studie sammanfoga hotellens hållbarhetsarbete med komplexiteten kring att hotell ingår i tjänsteindustrin och få en förståelse för vilka värderingar konsumenter har kring hållbarhet generellt och hur dessa värderingar relaterar till beteendet gällande bokning av hotell i synnerhet. Vidare undrar vi vad som skulle kunna motivera gäster att välja mer miljövänliga boendealternativ och hur, utifrån gästens värderingar, hotellen bör positionera sig. Detta undersöker vi genom att utföra en kvalitativ studie genom fokusgrupper och med en deduktiv forskningsansats i och med att vi utgår från tidigare forskning och teorier. Deltagarna i vår studie uppger att det för dem är ovanligt att relatera hotellbokning med hållbarhet men att det är intressant för dem att väcka dessa tankebanor. Resultatet visar också att de anser att hotellen har ett stort ansvar att vara miljömedvetna och hållbara men när det kommer till dem själva har vissa deltagare svårt att ta sitt ansvar fullt ut då hållbarhetsdebatten anses för ny för dem medan andra deltagare hävdar att det är rätt att tvingas göra aktiva val som väcker tankar hos individen om hur en kan påverka sin omvärld. Med det sagt så tyder resultatet av studien på att deltagarna har miljövänliga värderingar men att dessa värderingar inte alltid implementeras i beteendet, detta på grund av att vårt agerande baserad på vårt egna behov snarare än vad som är bra för hela världen. Deltagarna framhäver dock att i dagsläget så är det alltid pris och läge som kommer först när det gäller viktiga faktorer vid hotellbokning. Vi ser också tendenser i fokusgruppernas diskussioner som vi tolkar som att för att ett hotells arbete inom hållbarhet ska fungera behöver fyra faktorer uppfyllas. Arbetet skall vara Givande för gästen, Trovärdigt, Påtagligt och Utbildande.The world faces great challenges in the future due to how we overuse the resources of the earth. The environment of the earth and its sustainability is all that we as humans have and as the Bruntland report describes, it is important to act now in order to preserve the earth for future generations (WCED, 1987). At the same time, the awareness of climate change is increasing and with that, the impact that our actions have had so far on the climate. With that being said, a greater demand for responsibility is being called for, both for individuals and corporate businesses. For businesses it has become more normal to work with a tool called CSR, Corporate Social Responsibility, which integrates the environmental, social and economic responsibilities for the business and its activities. The private travelling increases more and more and with that also the need for staying at hotels. The stay at the hotel is what the guest consumes and because the stay is an experience that you physically cannot bring home with you, the hotel trade is a part of the service sector. Services are complex and there are challenges for the hotels in conveying the right information to the guest before he or she arrives to the hotel and letting them know what it actually is that they buy and pay for. In this study, we want to merge the hotels sustainability work with the complexity of being a service company. We also want to gain an understanding of which values consumers have regarding sustainability in general and how these values relate to the behavior when booking a hotel particularly. Further on, we wonder what could motivate guests to choose more environmentally friendly hotel options, and from the guest’s values, how hotels should position themselves. We investigate this by performing a qualitative study by using focus groups with a deductive approach, meaning that we base our work on previous studies and theories and uses them to draw conclusions of the result. The participants in our study declare that it is unusual to relate hotel booking with sustainability but at the same time they think that it is interesting to awake this way of thinking. The results also shows that the participants think that the hotels have a great responsibility in being sustainable but when they are to apply this on themselves, some participants struggle a bit more and meaning that the debate of sustainability is too young for them. In the other hand, several other participants think that it is right to be forced into making own decisions that raise awareness about how individuals can influence the world around themselves. With that being said, the result of the study points towards that the participants have environmentally values but that these values not always is being implemented in their behavior, probably because that we base our behavior on our own needs rather than what is good for the whole world. The participants point out that price and location always comes first when booking a hotel. Lastly, we see tendencies in the discussions in the focus groups which we interpret into four factors which hotels need to fulfill in order to conduct functional sustainability actions. The actions should be Awarding for the guest, Trustworthy, Tangible and Educational

“I expect to get free shipping”

Online shopping is today a very popular way of purchasing goods in Sweden, and two out of three Swedes are actively shopping online. When purchasing goods from a web shop, one important part of the process involves the delivery and potential return. There are in many cases delivery and return fees, also called shipping & handling costs, which the consumer sometimes must pay. These costs effect the consumers shopping behaviour in a way that they either can increase the amount of goods in the shopping cart or make the consumer reconsider the purchase. The aim of this paper is to get a deeper understanding of how the shipping & handling costs may affect the consumer’s decision when shopping online. The research was conducted through a mixed-method, combining both interviews and surveys. Our findings imply that shipping and handling costs do affect the consumers decision making online, and that the cost per see can determine whether or not they will go through with a purchase. Surprisingly, almost none of the consumers are interested in returning goods that they are unsatisfied with and especially not if there is a return fee. The majority of the consumers are aware of how it is possible to act sustainable, however, this is something that they almost never act upon when shopping online.MSc in Marketing & Consumptio

Long-term exposure to nicotine modulates the level and activity of acetylcholine receptors in white blood cells of smokers and model mice.

International audienceLong-term consumption of tobacco by smokers causes addiction and increases the level of neuronal nicotinic acetylcholine receptors (nAChRs) in the brain, a phenomenon known as up-regulation. Here, we show that up-regulation of specific nAChR subunits takes place in white blood cells (WBCs) of smokers and mice subjected to long-term administration of nicotine. The basal level of alpha-bungarotoxin binding site, which corresponds to the homomeric alpha7 nAChR subtype, was not affected in WBCs of both smokers and mice administered nicotine. In contrast, epibatidine (EB) binding sites, which correspond to heteromeric nAChR subtypes, were detected in WBCs of smokers but not in WBCs of nonsmokers. The number of EB binding sites significantly decreased after incubation of the smokers' WBCs for 3 days in nicotine-free culture medium. In WBCs of wild-type mice, basal level of EB binding sites was detected before nicotine administration. This basal level is reduced by approximately 60% in knockout mice lacking the genes encoding either the beta2 or the alpha4 receptor subunits. Additional analysis of knockout mice revealed that the remaining approximately 40% do not undergo up-regulation, indicating that the alpha4/beta2 subunits comprise the up-regulated nAChRs. We further found that upregulation in mouse WBCs is accompanied by a significant decrease in the capacity of the up-regulated receptor channels to convey calcium ions. The phenomenon of nAChR up-regulation in WBCs provides a simple tool to evaluate and study tobacco addiction