Radiokemian relevanssi : Tulevien radiokemistien käsityksiä

Radiokemi står inför en väldokumenterad utbildning och rekryteringskris. Äldre radiokemister går i pension och färre unga studerar radiokemi. I sin tur leder detta till brist på nyutbildade radiokemister, såväl som förlust av historisk kunskap (eftersom kunskap ofta inte förmedlas). Här analyserade vi relevansen av studien av radiokemi i högre utbildning genom framtida radiokemists uppfattningar. Vårt mål var att ge inblick i framtida radiokemisternas tänkande och ge några tydliga exempel på hur man stöder relevans. En kvalitativ studie genomfördes genom en forskningsfråga: Vilka uppfattningar om relevans upplever framtida radiokemister om radiokemistudier och radiokemi som fält? Vi använde relevansmodellen av Stuckey et al. (2013) som ram för relevans. Detta valdes eftersom det erbjuder en omfattande definition av relevans inklusive individuella, samhälleliga och yrkesmässiga dimensioner. Uppgifterna samlades in från forskarstudenter i radiokemi (magister- och doktorsexamen) genom användning av ett kvalitativt frågeformulär som utformades med den valda relevansramen. Totalt deltog 15 framtida radiokemister i studien. Uppgifterna analyserades genom teoribaserad innehållsanalys med användning av det valda relevansramverket. Enligt våra uppgifter upplever framtida radiokemister att deras universitetsstudier och kemifältet är mycket relevanta. De upplevde att ämnen för radiokemi är intressanta (individuell relevans), fältet har stor samhällseffekt genom radiofarmaceutika, energilösningar och miljöproblemlösning (samhällsrelevans) och att deras professionella framtid var tydlig, till exempel ett jobb inom kärnkraftsområdet industri (yrkesrelevans). Dessa resultat kan användas för studentrekrytering och för att utveckla radiokemiundervisning mot en mer relevant inriktning.Radiokemialla on koulutus- ja rekrytointikriisi. Vanhemmat radiokemistit siirtyvät eläkkeelle, ja yhä vähemmän nuoria valitsee radiokemiaa opiskelualakseen. Asetelman vuoksi on pulaa pätevistä radiokemisteistä, ja hiljaista tietoa häviää. Tässä tutkimuksessa selvitetään tulevien radiokemistien kokemuksia radiokemian relevanssista. Tavoitteena on selvittää, miksi radiokemiaa valinneet opiskelijat ovat alan valinneet. Tutkimus oli luonteeltaan laadullinen tutkimus. Aineisto kerättiin sähköpostikyselyillä sisältäen kaksi aineistonkeruusykliä. Ainesot analysoitiin teoriapohjaisella sisällnöanalyysillä tunnetun Stuckeyn et al. (2013) relevanssia hyödyntäen. Tutkimuksen mukaan tulevat radiokemistit kokivat alan erittäin relevanssiksi. He kokivat, että radiokemian olevan mielenkiintoista (henkilökohtainen relevanssi), radiokemian yhteiskunnallisen merkityksen olevan suuri esim. lääke- ja energiateollisuuden kautta (yhteiskunnallinen relevanssi) ja heillä oli selkeä kuva tulevaisuuden työllistymisestä (ammatillinen relevanssi). Tutkimuksen tuloksia voidaan käyttää opiskelijoiden rekrytointiin ja radiokemian opetuksen relevanssin vahvistamiseen.Radiochemistry faces a well-documented training and recruitment crisis. Older radiochemists are retiring, and fewer young people are studying radiochemistry. In turn, this is leading to a shortage in newly qualified radiochemists, as well as a loss of historical knowledge (as know-how is often not passed-on). Here, we analyzed the relevance of the study of radiochemistry in higher education through future radiochemists’ perceptions. Our objective was to provide insights into future radiochemists’ thinking and provide some clear examples on how to support relevance. A qualitative study was conducted through a research question: What perceptions of relevance do future radiochemists experience about radiochemistry studies and radiochemistry as a field? We used the relevance model of Stuckey et al. (2013) as the relevance framework. This was selected because it offers a comprehensive definition of relevance including individual, societal, and vocational dimensions. The data were gathered from postgraduate radiochemistry students (masters and Ph.D. level) through use of a qualitative questionnaire that was designed using the selected relevance framework. In total, 15 future radiochemists participated in the study. The data were analyzed through theory-based content analysis using the selected relevance framework. According to our data, future radiochemists experience their university study and the chemistry field as being highly relevant. They experienced that radiochemistry topics are interesting (individual relevance), the field has great societal impact through radiopharmaceuticals, energy solutions, and environmental problem-solving (societal relevance), and that their professional future was clear, for example, a job in the nuclear industry (vocational relevance). These results can be used in student recruitment and in developing radiochemistry teaching toward a more relevance-oriented direction.Peer reviewe

PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer

Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell’s responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention

Global Health Education: a cross-sectional study among German medical students to identify needs, deficits and potential benefits (Part 1 of 2: Mobility patterns & educational needs and demands)

<p>Abstract</p> <p>Background</p> <p>In recent years, education and training in global health has been the subject of recurring debate in many countries. However, in Germany, there has been no analysis of the educational needs or demands of medical students, or the educational deficits or potential benefits involved in global health education. Our purpose is to analyse international health elective patterns of medical students enrolled at German universities and assess whether or how they prepare for their electives abroad. We examine the exposure of medical students enrolled at German universities to training courses in tropical medicine or global health and assess students' perceived needs and demands for education in global health.</p> <p>Methods</p> <p>Cross-sectional study among medical students in Germany including all 36 medical schools during the second half of the year 2007. All registered medical students were eligible to participate in the study. Recruitment occurred via electronic mailing-lists of students' unions. We developed a web-based, semi-structured questionnaire to capture students' international mobility patterns, preparation before electives, destination countries, exposure to and demand for global health learning opportunities.</p> <p>Results</p> <p>1126 online-replies were received and analysed from all registered medical students in Germany (N = 78.067). 33.0% of all respondents (370/1126) declared at least one international health elective and of these, 36.0% (133/370) completed their electives in developing countries. 36.0% (131/363) did not prepare specifically at all, 59.0% (214/363) prepared either by self-study or declared a participation in specific preparation programmes. 87.8% of 5^thand 6^thyear students had never participated in a global health course and 72.6% (209/288) had not completed a course in tropical medicine. 94.0% (861/916) endorsed the idea of introducing global health into medical education.</p> <p>Conclusion</p> <p>Students in our sample are highly mobile during their studies. International health electives are common, also in developing countries. Formal preparation beyond self-study is virtually non-existent amongst our sample and the participation rate in courses of tropical medicine or global health is appallingly low. We have identified unmet perceived needs and the demand for more learning opportunities in global health in our sample, urging for reforms to adjust curricula to a globalising world.</p

Treatment with somatostatin analogs induces differentially expressed let-7c-5p and mir-3137 in small intestine neuroendocrine tumors

Background Distant metastases frequently occur in gastroenteropancreatic neuroendocrine tumors. If hepatic surgery is not feasible, patients are treated with somatostatin analogs. However, the underlying mechanisms of action of this treatment remain to be defined. The aim of the present study was to analyze the micro-RNA expression profile inter-individually before and after the treatment with somatostatin analogs. Material and methods Tumor specimens of all included patients (n = 8) before and after the onset of a therapy with somatostatin analogs were analyzed and a micro-RNA expression profile (754 micro-RNAs) of each probe was generated. This analysis in an intra-individual setting was selected to avoid bias from inter-individual differences. The micro-RNA expression profiles were validated by qPCR. Patients with any other systemic treatment were excluded from the present study. Results Eight patients were included in the present study of which all had neuroendocrine tumors of the small intestine with diffuse hepatic metastases. Grouped analyses revealed that 15 micro-RNAs were differentially expressed (3 up- and 12 downregulated) after the exposure to somatostatin analogs. Additionally, let-7c-5p and mir-3137 are concordantly regulated in the inter-individually analysis. Conclusions This is the first study analyzing the individual micro-RNA expression profile before and after a therapy with somatostatin analogs. Data from this study reveal that somatostatin analogs may in part exert their beneficial effects through an alteration in the micro-RNA expression profile

Proton-Assisted Amino Acid Transporter PAT1 Complexes with Rag GTPases and Activates TORC1 on Late Endosomal and Lysosomal Membranes

Mammalian Target of Rapamycin Complex 1 (mTORC1) is activated by growth factor-regulated phosphoinositide 3-kinase (PI3K)/Akt/Rheb signalling and extracellular amino acids (AAs) to promote growth and proliferation. These AAs induce translocation of mTOR to late endosomes and lysosomes (LELs), subsequent activation via mechanisms involving the presence of intralumenal AAs, and interaction between mTORC1 and a multiprotein assembly containing Rag GTPases and the heterotrimeric Ragulator complex. However, the mechanisms by which AAs control these different aspects of mTORC1 activation are not well understood. We have recently shown that intracellular Proton-assisted Amino acid Transporter 1 (PAT1)/SLC36A1 is an essential mediator of AA-dependent mTORC1 activation. Here we demonstrate in Human Embryonic Kidney (HEK-293) cells that PAT1 is primarily located on LELs, physically interacts with the Rag GTPases and is required for normal AA-dependent mTOR relocalisation. We also use the powerful in vivo genetic methodologies available in Drosophila to investigate the regulation of the PAT1/Rag/Ragulator complex. We show that GFP-tagged PATs reside at both the cell surface and LELs in vivo, mirroring PAT1 distribution in several normal mammalian cell types. Elevated PI3K/Akt/Rheb signalling increases intracellular levels of PATs and synergistically enhances PAT-induced growth via a mechanism requiring endocytosis. In light of the recent identification of the vacuolar H+-ATPase as another Rag-interacting component, we propose a model in which PATs function as part of an AA-sensing engine that drives mTORC1 activation from LEL compartments

Green Sturgeon Physical Habitat Use in the Coastal Pacific Ocean

The green sturgeon (Acipenser medirostris) is a highly migratory, oceanic, anadromous species with a complex life history that makes it vulnerable to species-wide threats in both freshwater and at sea. Green sturgeon population declines have preceded legal protection and curtailment of activities in marine environments deemed to increase its extinction risk. Yet, its marine habitat is poorly understood. We built a statistical model to characterize green sturgeon marine habitat using data from a coastal tracking array located along the Siletz Reef near Newport, Oregon, USA that recorded the passage of 37 acoustically tagged green sturgeon. We classified seafloor physical habitat features with high-resolution bathymetric and backscatter data. We then described the distribution of habitat components and their relationship to green sturgeon presence using ordination and subsequently used generalized linear model selection to identify important habitat components. Finally, we summarized depth and temperature recordings from seven green sturgeon present off the Oregon coast that were fitted with pop-off archival geolocation tags. Our analyses indicated that green sturgeon, on average, spent a longer duration in areas with high seafloor complexity, especially where a greater proportion of the substrate consists of boulders. Green sturgeon in marine habitats are primarily found at depths of 20–60 meters and from 9.5–16.0°C. Many sturgeon in this study were likely migrating in a northward direction, moving deeper, and may have been using complex seafloor habitat because it coincides with the distribution of benthic prey taxa or provides refuge from predators. Identifying important green sturgeon marine habitat is an essential step towards accurately defining the conditions that are necessary for its survival and will eventually yield range-wide, spatially explicit predictions of green sturgeon distribution