A platform for efficient, thiol-stable conjugation to albumin's native single accessible cysteine

Herein we report the use of bromomaleimides for the construction of stable albumin conjugates via conjugation to its native, single accessible, cysteine followed by hydrolysis. Advantages over the classical maleimide approach are highlighted in terms of quantitative hydrolysis and absence of undesirable retro-Michael deconjugation

Innovative solutions to enhance safe and green environments for ageing well using co-design through Patient and Public Involvement.

Background: There is a need to develop innovative solutions to enhance safe and green physical environments, which optimise health, wellbeing and community participation among older adults. In order to develop solutions that meet the needs of a diverse ageing population, an interdisciplinary approach is needed. Our aim was to identify the needs of older people in relation to ageing well in the environment by bringing together knowledge from different perspectives using Patient and Public Involvement. Methods: An international consortium (Retrofit living For ageing well through Understanding and Redesign of Built environments consortium: ReFURB) was established in April 2018, including ten core members, to (i) explore cutting-edge solutions to safe living for ageing populations and (ii) develop innovative approaches to everyday physical environments, which bring about health benefits. We used a co-design, interdisciplinary framework involving older adults, carers, physiotherapists, geriatricians, engineers, human movement experts, geographers and psychologists from the UK and Australia. This engaged people in a one day workshop that comprised a series of presentations from international speakers on urban design, social connectedness, hazards and injury prevention, and the physical environment. Small group discussions (facilitated by consortium members) followed presentations to consider the opportunities, challenges and barriers encountered with ageing, which included the use of creative engagement activities (LEGO® Serious Play, mind maps, poster gallery walk), to help participants share personal stories and reflect on the issues raised. Thematic coding was used to synthesise the outputs of the small group work. Results: Five themes were identified across the workshops, comprising: access and transport; involvement of the whole community; restoration rather than redesign; assistive and digital technology; and intergenerational approaches. These dimensions related to the physical, social and nature-based qualities of everyday environments, as they pertain to ageing well. Conclusions: Co-design was a valuable tool that helped understand the perceptions of participants and essential to develop effective interventions and solutions. Participants highlighted several issues affecting people as they age and key environmental considerations to promote wellbeing, activity, and participation. The consortium identified gaps in the existing evidence base and are now planning activities to further develop research ideas in collaboration with our co-design participants

Basophil competence during hookworm (Necator americanus) infection

A popular hypothesis to explain parasite survival in the presence of a pronounced T helper 2 phenotype in helminth-parasitized populations has been Fc epsilon RI blockade by parasite-induced polyclonal IgE. To begin to test the hypothesis that Fc epsilon RI-bearing cells would be refractory to activation in parasitized populations, we investigated basophil function in 43 individuals from a hookworm endemic area. Study individuals had high levels of total IgE and eosinophilia and a mean hookworm burden of 2,257 epg. Basophils from all members of this parasitized population were shown to release histamine to a number of agonists, including anti IgE and a hookworm allergen, calreticulin. These data would indicate that Fc epsilon RI blockade at the level of the basophil did not occur in this parasitized population despite the presence of possible immunologic blocking agents. This would suggest that this effector arm of the T helper 2 phenotype remains operative in infected populations

Burial and exhumation history of a Lesser Himalayan schist: Recording the formation of an inverted metamorphic sequence in NW India

Coupled analysis of the pressure–temperature (PT) evolution and accessory phase geochronology of a single sample reveals the burial-uplift history of part of the Lesser Himalaya during the Middle Miocene. Phase-equilibria calculations indicate that a peak temperature of 600–640 °C followed burial to approximately 25 km depth. Laser-ablation monazite geochronology yields a weighted mean 206Pb/238U age of 11.1 ± 2.0 Ma and a Tera-Wasserburg Concordia intercept age of 10.6 ± 0.9 Ma, with no distinguishable age difference between matrix and inclusion grains. Considerations of the likelihood of excess 206Pb further suggest that the crystallization age lies in the range 9–10 Ma. Textural analysis suggests that monazite grew during prograde metamorphism. Peak metamorphic conditions were followed by exhumation and cooling, forming a distinctively tight PT path closure. Both the shape of this path and its relatively young prograde phase distinguish Lesser Himalayan evolution from that typically inferred for the High Himalaya, and allow exploration of the thermal mechanisms that operated in the western Himalaya during the interval ca. 23–6 Ma. The PTt history is characteristic of footwall heating due to rapid overthrusting of hot rock (the Higher Himalaya), followed by incorporation into a thrust sheet that exhumed the sequence rapidly enough to preserve an inverted metamorphic gradient

The power of words

Are books in the realm of science influential enough to affect or (mis)inform public opinion