Bespoke Biomolecular Wires for Transmembrane Electron Transfer: Spontaneous Assembly of a Functionalized Multiheme Electron Conduit.

Shewanella oneidensis exchanges electrons between cellular metabolism and external redox partners in a process that attracts much attention for production of green electricity (microbial fuel cells) and chemicals (microbial electrosynthesis). A critical component of this pathway is the outer membrane spanning MTR complex, a biomolecular wire formed of the MtrA, MtrB, and MtrC proteins. MtrA and MtrC are decaheme cytochromes that form a chain of close-packed hemes to define an electron transfer pathway of 185 Å. MtrA is wrapped inside MtrB for solubility across the outer membrane lipid bilayer; MtrC sits outside the cell for electron exchange with external redox partners. Here, we demonstrate tight and spontaneous in vitro association of MtrAB with separately purified MtrC. The resulting complex is comparable with the MTR complex naturally assembled by Shewanella in terms of both its structure and rates of electron transfer across a lipid bilayer. Our findings reveal the potential for building bespoke electron conduits where MtrAB combines with chemically modified MtrC, in this case, labeled with a Ru-dye that enables light-triggered electron injection into the MtrC heme chain

Towards compartmentalized photocatalysis: multihaem proteins as transmembrane molecular electron conduits.

The high quantum efficiency of natural photosynthesis has inspired chemists for solar fuel synthesis. In photosynthesis, charge recombination in photosystems is minimized by efficient charge separation across the thylakoid membrane. Building on our previous bioelectrochemical studies of electron transfer between a light-harvesting nanoparticle (LHNP) and the decahaem subunit MtrC, we demonstrate photo-induced electron transfer through the full transmembrane MtrCAB complex in liposome membranes. Successful photoelectron transfer is demonstrated by the decomposition of a redox dye, Reactive Red 120 (RR120), encapsulated in MtrCAB proteoliposomes. The photoreduction rates are found to be dependent on the identity of the external LHNPs, specifically, dye-sensitized TiO2, amorphous carbon dots (a-CD) and graphitic carbon dots with core nitrogen doping (g-N-CDs). Agglomeration or aggregation of TiO2 NPs likely reduces the kinetics of RR120 reductive decomposition. In contrast, with the dispersed a-CD and g-N-CDs, the kinetics of the RR120 reductive decomposition are observed to be faster with the MtrCAB proteoliposomes and we propose that this is due to enhancement in the charge-separated state. Thus, we show a proof-of-concept for using MtrCAB as a lipid membrane-spanning building block for compartmentalised photocatalysis that mimics photosynthesis. Future work is focused on incorporation of fuel generating redox catalysts in the MtrCAB proteoliposome lumen.This work was supported by the BBSRC (DTP studentship 1827308; grants BB/ K009753/1, BB/K010220/1 and BB/K009885/1) and the Engineering and Physical Sciences Research Council (PhD studentship 1307196)

The writing on the wall: the concealed communities of the East Yorkshire horselads

This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor

Oral vitamin B(12 )therapy in the primary care setting: a qualitative and quantitative study of patient perspectives

BACKGROUND: Although oral replacement with high doses of vitamin B(12 )is both effective and safe for the treatment of B(12 )deficiency, little is known about patients' views concerning the acceptability and effectiveness of oral B(12). We investigated patient perspectives on switching from injection to oral B(12 )therapy. METHODS: This study involved a quantitative arm using questionnaires and a qualitative arm using semi-structured interviews, both to assess patient views on injection and oral therapy. Patients were also offered a six-month trial of oral B(12 )therapy. One hundred and thirty-three patients who receive regular B(12 )injections were included from three family practice units (two hospital-based academic clinics and one community health centre clinic) in Toronto. RESULTS: Seventy-three percent (63/86) of respondents were willing to try oral B(12). In a multivariate analysis, patient factors associated with a "willingness to switch" to oral B(12 )included being able to get to the clinic in less than 30 minutes (OR 9.3, 95% CI 2.2–40.0), and believing that frequent visits to the health care provider (OR 5.4, 95% CI 1.1–26.6) or the increased costs to the health care system (OR 16.7, 95% CI 1.5–184.2) were disadvantages of injection B(12). Fifty-five patients attempted oral therapy and 52 patients returned the final questionnaire. Of those who tried oral therapy, 76% (39/51) were satisfied and 71% (39/55) wished to permanently switch. Factors associated with permanently switching to oral therapy included believing that the frequent visits to the health care provider (OR 35.4, 95% CI 2.9–432.7) and travel/parking costs (OR 8.7, 95% CI 1.2–65.3) were disadvantages of injection B(12). Interview participants consistently cited convenience as an advantage of oral therapy. CONCLUSION: Switching patients from injection to oral B(12 )is both feasible and acceptable to patients. Oral B(12 )supplementation is well received largely due to increased convenience. Clinicians should offer oral B(12 )therapy to their patients who are currently receiving injections, and newly diagnosed B(12)-deficient patients who can tolerate and are compliant with oral medications should be offered oral supplementation

“It is all about the fear of being discriminated [against]…the person suffering from HIV will not be accepted”: a qualitative study exploring the reasons for loss to follow-up among HIV-positive youth in Kisumu, Kenya

BACKGROUND: Youth represent 40% of all new HIV infections in the world, 80% of which live in sub-Saharan Africa. Youth living with HIV (YLWH) are more likely to become lost to follow-up (LTFU) from care compared to all other age groups. This study explored the reasons for LTFU among YLWH in Kenya. METHODS: Data was collected from: (1) Focus group Discussions (n = 18) with community health workers who work with LTFU youth. (2) Semi-structured interviews (n = 27) with HIV + youth (15–21 years old) that had not received HIV care for at least four months. (3) Semi-structured interviews (n = 10) with educators selected from schools attended by LTFU interview participants. Transcripts were coded and analyzed employing grounded theory. RESULTS: HIV-related stigma was the overarching factor that led to LTFU among HIV + youth. Stigma operated on multiple levels to influence LTFU, including in the home/family, at school, and at the clinic. In all three settings, participants’ fear of stigma due to disclosure of their HIV status contributed to LTFU. Likewise, in the three settings, the dependent relationships between youth and the key adult figures in their lives were also adversely impacted by stigma and resultant lack of disclosure. Thus, at all three settings stigma influenced fear of disclosure, which in turn impacted negatively on dependent relationships with adults on whom they rely (i.e. parents, teachers and clinicians) leading to LTFU. CONCLUSIONS: Interventions focusing on reduction of stigma, increasing safe disclosure of HIV status, and improved dependent relationships may improve retention in care of YLWH

Heat Resistance Mediated by a New Plasmid Encoded Clp ATPase, ClpK, as a Possible Novel Mechanism for Nosocomial Persistence of Klebsiella pneumoniae

Klebsiella pneumoniae is an important opportunistic pathogen and a frequent cause of nosocomial infections. We have characterized a K. pneumoniae strain responsible for a series of critical infections in an intensive care unit over a two-year period. The strain was found to be remarkably thermotolerant providing a conceivable explanation of its persistence in the hospital environment. This marked phenotype is mediated by a novel type of Clp ATPase, designated ClpK. The clpK gene is encoded by a conjugative plasmid and we find that the clpK gene alone renders an otherwise sensitive E. coli strain resistant to lethal heat shock. Furthermore, one third of a collection of nosocomial K. pneumoniae isolates carry clpK and exhibit a heat resistant phenotype. The discovery of ClpK as a plasmid encoded factor and its profound impact on thermal stress survival sheds new light on the biological relevance of Clp ATPases in acquired environmental fitness and highlights the challenges of mobile genetic elements in fighting nosocomial infections

'This is our Call of Duty': hegemony, history and resistant videogames in the Middle East

In recent years, non-state actors in the Middle East have engaged a new generation of activists through a variety of media strategies. Notable among these is a series of videogame interventions, which have appropriated Western game products to convey political and religious messages through the inversion or complication of the roles of hero and enemy. This article explores a selection of such media, produced by or in support of two non-state groups, Hezbollah and Islamic State (IS). The article takes a discourse theoretical approach to examine the ideologies presented in these media and reflects on the ways in which these game artefacts engage with, and reject, Western narratives of history and of US pre-eminence. It concludes that while these game interventions challenge existing hegemonic (re)presentations of the Middle East and the ‘War on Terror’, they remove or reduce agency to the extent that those who engage with them can only witness these challenges, rather than instigate their own. While we acknowledge that hegemony can always be challenged, we view this lack of agency as support for Mouffe’s proposition that the result of counter-hegemonic resistance is often to maintain and reproduce the hegemonic order

The catatonic dilemma expanded

Catatonia is a common syndrome that was first described in the literature by Karl Kahlbaum in 1874. The literature is still developing and remains unclear on many issues, especially classification, diagnosis, and pathophysiology. Clinicians caring for psychiatric patients with catatonic syndromes continue to face many dilemmas in diagnosis and treatment. We discuss many of the common problems encountered in the care of a catatonic patient, and discuss each problem with a review of the literature. Focus is on practical aspects of classification, epidemiology, differential diagnosis, treatment, medical comorbidity, cognition, emotion, prognosis, and areas for future research in catatonic syndromes

Anisotropic Heterobimetallic Nanomaterials with Controlled Composition for Efficient Oxygen Reduction at Ultralow Loading

Publication status: PublishedFunder: European Commission for a Horizon 2020 Marie Skłodowska‐Curie Individual European FellowshipFunder: Jesus College, University of Cambridge; doi: http://dx.doi.org/10.13039/501100000644Funder: China Scholarship Council; doi: http://dx.doi.org/10.13039/501100004543AbstractHydrogen fuel cells represent a leading technology in developing green energy targeting net‐zero emissions goals by mid‐century. However, the sluggish kinetics of the oxygen reduction reaction (ORR) have hitherto demanded substantial quantities of expensive platinum (Pt) group metals. Advances in catalyst design, including the controllable fabrication of highly branched morphologies to increase the surface area‐to‐volume ratio, intermixing Pt with more affordable transition metals, and controlling composition, offer solutions that can further enhance activity and reduce expense. In this context, Pt/M (M = Fe, Ni, Co) nanopods and nanodendrites with precise composition control using more affordable starting materials are designed and crafted. The method is highly efficient, taking only 30 min and avoiding the need for high‐pressure equipment, making it highly scalable. These catalysts show superior ORR performance at an electrode loading as low as 0.0022 mgPt cm−2. One, nanodendritic Pt/Ni, achieves a mass activity of at 0.9 V versus RHE, making it 87 times more efficient in terms of Pt‐content than a commercial 10 wt% Pt/C nanoparticle standard. These findings provide new opportunities for developing next‐generation, cost‐efficient Pt‐based catalysts, by potentially advancing hydrogen fuel cell technology through performance enhancement and addressing cost challenges through catalyst design.</jats:p