A novel analytical ultracentrifugation based approach to the low resolution structure of gum arabic

Under investigation are the structural properties of gum arabic, an industrially important biopolymer for use as a stabilizer or in drug delivery, using Analytical Ultracentrifugation—a well-established, matrix-free probe for macromolecular size and shape. These results are combined with chromatographically-coupled methods (multi-angle light scattering, differential press imbalance viscometry) to provide a global analysis of its structure in varying ionic strength conditions. This analysis indicates that gum Arabic may have a compact, elliptical structure in solution, the significance of which for biotechnological use is indicated. This modelling method can be applied to other biopolymers and synthetic polymers

The effectiveness of lifestyle adaptation for the prevention of prediabetes in adults: a systematic review

Diabetes prevalence is increasing exceptionally worldwide and with this come associated healthcare costs. The primary outcome of this systematic review was to assess glycaemic control and incidence of Type 2 diabetes mellitus (T2DM) diagnosis after exercise and dietary intervention (measured with any validated scale). The secondary outcome assessed body mass index change, weight change, and physical exercise capacity after diet and exercise intervention (measured with any validated scale). 1,780 studies were identified from searching electronic databases. Relevant studies went through a selection process. The inclusion criteria for all studies were people with prediabetes diagnosed by either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). Lifestyle adaptation reduced the incidence of diabetes development more than standard treatment. Furthermore, better glycaemic control, improved physical exercise capacity, and increased weight reduction were observed with lifestyle intervention over standard treatment. Finally, improvements over the long term deteriorated, highlighting problems with long-term adherence to lifestyle changes. Overall, cumulative incidence of diabetes is drastically reduced in the intervention groups compared to control groups (standard care). Furthermore, glycaemic control was improved in the short term, with many participants reverting to normoglycaemia

Characterisation of insulin analogues therapeutically available to patients

The structure and function of clinical dosage insulin and its analogues were assessed. This included ‘native insulins’ (human recombinant, bovine, porcine), ‘fast-acting analogues’ (aspart, glulisine, lispro) and ‘slow-acting analogues’ (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Elution from SEC plots of insulin and analogues.

<p>Black line represents PBS as the mobile phase, grey line represents TRIS. (a) IHr; (b) IBov; (c) IPor; (d) IAsp; (e) IGlu; (f) ILis; (g) IDet; (h) IDeg. IGla was not injected due to pI/pH incompatibilities. Monomers (M), Dimers (D), Hexamers (H), Dihexamers (DiH), multihexamers (multiH) and Excipients (Ex) were identified by molar mass.</p

c(M) vs. molar mass distributions measured using SEDFIT-MSTAR from AUC-SE data, with superimposed M*(r) extrapolations to the cell base (relative radius = 1), and c(M) fits over raw AUC-SE data in insets.

<p>(a) IHr; (b) IBov; (c) IPor; (d) IAsp; (e) IGlu; (f) ILis; (g) IGla; (h) IDet; (i) IDeg. SEDFIT-MSTAR was unable to adequately fit data from IDeg.</p

Hydrodynamic parameters measured using AUC-SV and AUC-SE.

<p>Sedimentation coefficients are weight-averaged in the cases of multi-species distributions. IGlu and IDet yielded fits with BM<0. All insulins were measured at ~3.5mg/mL, except for IDet which was measured at 14.2mg/mL.</p

c(s) vs. sedimentation coefficient distributions measured using AUC-SV at 45k rpm.

<p>(a) Native insulins; (b) Rapid-acting analogues; (c) Slow-acting analogues. Monomers (M), Dimers (D), Hexamers (H), and Di and Tri Hexamers (Di/TriH) were identified by molar mass calculated through the sedimentation coefficient and the frictional ratio.</p

Weight-average molar mass estimates from AUC-SV, AUC-SE and SEC-MALS results.

<p>Estimates uncorrected for non-ideality are labelled ‘apparent’ (_app). All AUC-SV estimates were made on data from 45k rpm and based upon estimates of the frictional ratio fitted from boundary spread, and are weight averaged in the case of multiple sedimenting species. AUC-SE analysis was made at the indicated rotor speeds in parentheses (k rpm). SEC-MALS estimates are shown as consensus values from PBS and TRIS mobile phases. IDeg was unanalysable using MSTAR and MULTISIG. IGla was not assayed using SEC-MALS due to pI/pH incompatibilities.</p

Primary structure of human insulin and its analogues.

<p>Differences highlighted and numbered.</p