The South Atlantic in the Fine-Resolution Antarctic Model

The geographical area covered by the Fine-Resolution Antarctic Model (FRAM) includes that part of the South Atlantic south of 24°S. A description of the dynamics and thermodynamics of this region of the model is presented. Both the mean and eddy fields in the model are in good agreement with reality, although the magnitude of the transients is somewhat reduced. The heat flux is northward and in broad agreement with many other estimates. Agulhas eddies are formed by the model and propagate westward into the Atlantic providing a mechanism for fluxing heat from the Indian Ocean. The confluence of the Brazil and Falkland currents produces a strong front and a large amount of mesoscale activity. In the less stratified regions to the south, topographic steering of the Antarctic circumpolar current is important

Fabricating electrospun cellulose nanofibre adsorbents for ion-exchange chromatography

Protein separation is an integral step in biopharmaceutical manufacture with diffusion-limited packed bed chromatography remaining the default choice for industry. Rapid bind-elute separation using convective mass transfer media offers advantages in productivity by operating at high flowrates. Electrospun nanofibre adsorbents are a non-woven fibre matrix of high surface area and porosity previously investigated as a bioseparation medium. The effects of compression and bed layers, and subsequent heat treatment after electrospinning cellulose acetate nanofibres were investigated using diethylaminoethyl (DEAE) or carboxylate (COO) functionalisations. Transbed pressures were measured and compared by compression load, COO adsorbents were 30%, 70% and 90% higher than DEAE for compressions 1, 5 and 10 MPa, respectively, which was attributed to the swelling effect of hydrophilic COO groups. Dynamic binding capacities (DBCs) at 10% breakthrough were measured between 2000 and 12,000 CV/h (2 s and 0.3 s residence times) under normal binding conditions, and DBCs increased with reactant concentration from 4 to 12 mg BSA/mL for DEAE and from 10 to 21 mg lysozyme/mL for COO adsorbents. Comparing capacities of compression loads applied after electrospinning showed that the lowest load tested, 1 MPa, yielded the highest DBCs for DEAE and COO adsorbents at 20 mg BSA/mL and 27 mg lysozyme/mL, respectively. At 1 MPa, DBCs were the highest for the lowest flowrate tested but stabilised for flowrates above 2000 CV/h. For compression loads of 5 MPa and 10 MPa, adsorbents recorded lower DBCs than 1 MPa as a result of nanofibre packing and reduced surface area. Increasing the number of bed layers from 4 to 12 showed decreasing DBCs for both adsorbents. Tensile strengths were recorded to indicate the mechanical robustness of the adsorbent and be related to packing the nanofibre adsorbents in large scale configurations such as pleated cartridges. Compared with an uncompressed adsorbent, compressions of 1, 5 and 10 MPa showed increases of 30%, 110% and 110%, respectively, for both functionalisations. The data presented show that capacity and mechanical strength can be balanced through compression after electrospinning and is particular to different functionalisations. This trade-off is critical to the development of nanofibre adsorbents into different packing configurations for application and scale up in bioseparation

Multiple Myeloma

The results of the use of melphalan in 52 patients with multiple myeloma have been analysed. The median survival of the whole group of patients was 30 months, and of those w:th renal insufficiency only 12,5 months. Bence-lones proteinuria was also a poor prognostic finding,. but only because of its association with renal failure. Patients with Bence-Jones protcinur;a and normal renal function had a median survival of 41 months. Responsiveness to therapy by criteria based on those of the Chronic Leukemial Multip!e Myeloma Task Force could be assessed in 25 patients. Dramatic symptomatic relief occurred in all but one of the responsive patients, but in only one-fifth of those who did not respond to therapy.S. Afr. Med. J., 48, 1026 (1974

Multiple Myeloma

The clinical, biochemical and immunochemical features of 52 patients suffering from multiple myelomatosis are reported. Three major criteria were used to establish the diagnosis: serum and urine protein chemistry, bone marrow morphology and the radiological appearances of bone. The fact that abnormalities of gamma globulin synthesis were present in 49 of the 52 patients indicates the importance of adequate examination of urine by electrophores's and immunochemical techniques in the early diagnosis of multiple myeloma. Bradshaw's test, which is a simple screening test for fence-Jones proteinuria, was positive in 63% of patients.S. Afr. Med. J., 48, 1023 (1974)

Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1

Oxidative cyclization of tertiary pentenol derivatives forming 2,5,5-trisubstituted THF rings and the total synthesis of cyclocapitelline

The synthesis of 2,5,5-trisubstituted tetrahydrofuran rings was accomplished via the Mukaiyama aerobic oxidative cyclization of tertiary 5-pentenols employing the Co(nmp)2catalyst. A variety of THFs were formed in moderate to good yield and diastereoselectivity. The method developed herein was successfully applied to an enantioselective total synthesis of cyclocapitelline

Molecular imaging of extracellular vesicles in vitro via Raman metabolic labelling

Extracellular vesicles (EVs) are biologically-derived nanovectors important for intercellular communication and trafficking. As such, EVs show great promise as disease biomarkers and therapeutic drug delivery vehicles. However, despite the rapidly growing interest in EVs, understanding of the biological mechanisms that govern their biogenesis, secretion, and uptake remains poor. Advances in this field have been hampered by both the complex biological origins of EVs, which make them difficult to isolate and identify, and a lack of suitable imaging techniques to properly study their diverse biological roles. Here, we present a new strategy for simultaneous quantitative in vitro imaging and molecular characterisation of EVs in 2D and 3D based on Raman spectroscopy and metabolic labelling. Deuterium, in the form of deuterium oxide (D2O), deuterated choline chloride (d-Chol), or deuterated D-glucose (d-Gluc), is metabolically incorporated into EVs through the growth of parent cells on medium containing one of these compounds. Isolated EVs are thus labelled with deuterium, which acts as a bio-orthogonal Raman-active tag for direct Raman identification of EVs when introduced to unlabelled cell cultures. Metabolic deuterium incorporation demonstrates no apparent adverse effects on EV secretion, marker expression, morphology, or global composition, indicating its capacity for minimally obstructive EV labelling. As such, our metabolic labelling strategy could provide integral insights into EV biocomposition and trafficking. This approach has the potential to enable a deeper understanding of many of the biological mechanisms underpinning EVs, with profound implications for the design of EVs as therapeutic delivery vectors and applications as disease biomarkers

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration

Gender perspectives on views and preferences of older people on exercise to prevent falls: a systematic mixed studies review

Background: To offer fall prevention exercise programs that attract older people of both sexes there is a need to understand both womens and mens views and preferences regarding these programs. This paper aims to systematically review the literature to explore any underlying gender perspectives or gender interpretations on older peoples views or preferences regarding uptake and adherence to exercise to prevent falls. Methods: A review of the literature was carried out using a convergent qualitative design based on systematic searches of seven electronic databases (PubMed, CINAHL, Amed, PsycINFO, Scopus, PEDro, and OTseeker). Two investigators identified eligible studies. Each included article was read by at least two authors independently to extract data into tables. Views and preferences reported were coded and summarized in themes of facilitators and barriers using a thematic analysis approach. Results: Nine hundred and nine unique studies were identified. Twenty five studies met the criteria for inclusion. Only five of these contained a gender analysis of mens and womens views on fall prevention exercises. The results suggests that both women and men see women as more receptive to and in more need of fall prevention messages. The synthesis from all 25 studies identified six themes illustrating facilitators and six themes describing barriers for older people either starting or adhering to fall prevention exercise. The facilitators were: support from professionals or family; social interaction; perceived benefits; a supportive exercise context; feelings of commitment; and having fun. Barriers were: practical issues; concerns about exercise; unawareness; reduced health status; lack of support; and lack of interest. Considerably more women than men were included in the studies. Conclusion: Although there is plenty of information on the facilitators and barriers to falls prevention exercise in older people, there is a distinct lack of studies investigating differences or similarities in older womens and mens views regarding fall prevention exercise. In order to ensure that fall prevention exercise is appealing to both sexes and that the inclusion of both men and women are encouraged, more research is needed to find out whether gender differences exists and whether practitioners need to offer a range of opportunities and support strategies to attract both women and men to falls prevention exercise.Funding Agencies|Swedish Research Council [2015-03481]; Strategic Research Programme in Care Sciences, Umea University; Karolinska Institute, Sweden; Umea University</p