House of Commons Science and Technology Select Committee Session 2012-13, Forensic Science, Minutes of Evidence HC 930-ii, Oral Evidence, 6th February 2013

House of Commons Science and Technology Select Committee Session 2012-13, Forensic Science, Minutes of Evidence HC 930-ii, Oral Evidence, 6th February 201

Highly Scalable, Closed-Loop Synthesis of Drug-Loaded, Layer-by-Layer Nanoparticles

Layer-by-layer (LbL) self-assembly is a versatile technique from which multi­component and stimuli-responsive nanoscale drug-carriers can be constructed. Despite the benefits of LbL assembly, the conventional synthetic approach for fabricating LbL nanoparticles requires numerous purification steps that limit scale, yield, efficiency, and potential for clinical translation. In this report, a generalizable method for increasing throughput with LbL assembly is described by using highly scalable, closed-loop diafiltration to manage intermediate purification steps. This method facilitates highly controlled fabrication of diverse nanoscale LbL formulations smaller than 150 nm composed from solid-polymer, mesoporous silica, and liposomal vesicles. The technique allows for the deposition of a broad range of polyelectrolytes that included native polysaccharides, linear polypeptides, and synthetic polymers. The cytotoxicity, shelf life, and long-term storage of LbL nanoparticles produced using this approach are explored. It is found that LbL coated systems can be reliably and rapidly produced: specifically, LbL-modified liposomes could be lyophilized, stored at room temperature, and reconstituted without compromising drug encapsulation or particle stability, thereby facilitating large scale applications. Overall, this report describes an accessible approach that significantly improves the throughput of nanoscale LbL drug-carriers that show low toxicity and are amenable to clinically relevant storage conditions.National Institutes of Health (U.S.) (Grant 1F32EB017614–02)Swiss National Science Foundation (Postdoctoral Fellowship

Functional basis of electron transport within photosynthetic complex I

Photosynthesis and respiration rely upon a proton gradient to produce ATP. In photosynthesis, the Respiratory Complex I homologue, Photosynthetic Complex I (PS-CI) is proposed to couple ferredoxin oxidation and plastoquinone reduction to proton pumping across thylakoid membranes. However, little is known about the PS-CI molecular mechanism and attempts to understand its function have previously been frustrated by its large size and high lability. Here, we overcome these challenges by pushing the limits in sample size and spectroscopic sensitivity, to determine arguably the most important property of any electron transport enzyme – the reduction potentials of its cofactors, in this case the iron-sulphur clusters of PS-CI (N0, N1 and N2), and unambiguously assign them to the structure using double electron-electron resonance. We have thus determined the bioenergetics of the electron transfer relay and provide insight into the mechanism of PS-CI, laying the foundations for understanding of how this important bioenergetic complex functions

Expanded binding specificity of the human histone chaperone NASP

NASP (nuclear autoantigenic sperm protein) has been reported to be an H1-specific histone chaperone. However, NASP shares a high degree of sequence similarity with the N1/N2 family of proteins, whose members are H3/H4-specific histone chaperones. To resolve this paradox, we have performed a detailed and quantitative analysis of the binding specificity of human NASP. Our results confirm that NASP can interact with histone H1 and that this interaction occurs with high affinity. In addition, multiple in vitro and in vivo experiments, including native gel electrophoresis, traditional and affinity chromatography assays and surface plasmon resonance, all indicate that NASP also forms distinct, high specificity complexes with histones H3 and H4. The interaction between NASP and histones H3 and H4 is functional as NASP is active in in vitro chromatin assembly assays using histone substrates depleted of H1

Seals and shipping : quantifying population risk and individual exposure to vessel noise

The work was funded under Scottish Government grant MMSS/001/11 and contract CR/2014/04, and supported by National Capability funding from NERC to SMRU (grant no. SMRU1001). Seal at-sea usage maps, location data for individual seals, locations and source levels for vessels, and SPLs from monitoring data used for acoustic validations are available from the Pure repository, https://doi.org/10.17630/89ac9345-240a-41bb-8f53-b3f14bb114c0.1.  Vessels can have acute and chronic impacts on marine species. The rate of increase in commercial shipping is accelerating, and there is a need to quantify and potentially manage the risk of these impacts. 2.  Usage maps characterising densities of grey and harbour seals and ships around the British Isles were used to produce risk maps of seal co-occurrence with shipping traffic. Acoustic exposure to individual harbour seals was modelled in a study area using contemporaneous movement data from 28 animals fitted with UHF global positioning satellite telemetry tags and automatic identification system data from all ships during 2014 and 2015. Data from four acoustic recorders were used to validate sound exposure predictions. 3.  Across the British Isles, rates of co-occurrence were highest within 50 km of the coast, close to seal haul-outs. Areas identified with high risk of exposure included 11 Special Areas of Conservation (SAC; from a possible 25). Risk to harbour seal populations was highest, affecting half of all SACs associated with the species. 4.  Predicted cumulative sound exposure level, cSELs(Mpw), over all seals was 176·8 dB re 1 μPa2 s (95% CI 163·3–190·4), ranging from 170·2 dB re 1μPa2 s (95% CI 168·4–171·9) to 189·3 dB re 1 μPa2 s (95% CI 172·6–206·0) for individuals. This represented an increase in 28·3 dB re 1 μPa2 s over measured ambient noise. For 20 of 28 animals in the study, 95% CI for cSELs(Mpw) had upper bounds above levels known to induce temporary threshold shift. Predictions of broadband received sound pressure levels were underestimated on average by 0·7 dB re 1 μPa (±3·3). 5. Synthesis and applications. We present a framework to allow shipping noise, an important marine anthropogenic stressor, to be explicitly incorporated into spatial planning. Potentially sensitive areas are identified through quantifying risk to marine species of exposure to shipping traffic, and individual noise exposure is predicted with associated uncertainty in an area with varying rates of co-occurrence. The detailed approach taken here facilitates spatial planning with regard to underwater noise within areas protected through the Habitats Directive, and could be used to provide evidence for further designations. This framework may have utility in assessing whether underwater noise levels are at Good Environmental Status under the Marine Strategy Framework Directive.Publisher PDFPeer reviewe

Classification and identification of Pfiesteria and Pfiesteria-like species.

Dinoflagellates can be classified both botanically and zoologically; however, they are typically put in the botanical division Pyrrhophyta. As a group they appear most related to the protistan ciliates and apicomplexans at the ultrastructure level. Within the Pyrrhophyta are both unarmored and armored forms of the dominant, motile flagellated stage. Unarmored dinoflagellates do not have thecal or wall plates arranged in specific series, whereas armored species have plates that vary in thickness but are specific in number and arrangement. In armored dinoflagellates, the plate pattern and tabulation is a diagnostic character at the family, subfamily, and even genus levels. In most cases, the molecular characterization of dinoflagellates confirms the taxonomy on the basis of external morphology; this has been demonstrated for several groups. Together, both genetic and morphological criteria are becoming increasingly important for the characterization, separation, and identification of dinoflagellates species. Pfiesteria and Pfiesteria-like species are thinly armored forms with motile dinospore stages characterized by their distinct plate formulae. Pfiesteria piscicida is the best-known member of the genus; however, there is at least one other species. Other genetically and morphologically related genera, now grouped under the common names of "Lucy," "Shepherd's crook," and cryptoperidiniopsoid, are being studied and described in separate works. All these other heterotrophic dinoflagellate groups, many of which are thought to be benign, co-occur in estuarine waters where Pfiesteria has been found

Classification and Identification of Pfiesteria and Pfiesteria-Like Species

Dinoflagellates can be classified both botanically and zoologically; however, they are typically put in the botanical division Pyrrhophyta. As a group they appear most related to the protistan ciliates and apicomplexans at the ultrastructure level. Within the Pyrrhophyta are both unarmored and armored forms of the dominant, motile flagellated stage. Unarmored dinoflagellates do not have thecal or wall plates arranged in specific series, whereas armored species have plates that vary in thickness but are specific in number and arrangement. In armored dinoflagellates, the plate pattern and tabulation is a diagnostic character at the family, subfamily, and even genus levels. In most cases, the molecular characterization of dinoflagellates confirms the taxonomy on the basis of external morphology; this has been demonstrated for several groups. Together, both genetic and morphological criteria are becoming increasingly important for the characterization, separation, and identification of dinoflagellates species. Pfiesteria and Pfiesteria-like species are thinly armored forms with motile dinospore stages characterized by their distinct plate formulae. Pfiesteria piscicida is the best-known member of the genus; however, there is at least one other species. Other genetically and morphologically related genera, now grouped under the common names of Lucy, Shepherd\u27s crook, and cryptoperidiniopsoid, are being studied and described in separate works. All these other heterotrophic dinoflagellate groups, many of which are thought to be benign, co-occur in estuarine waters where Pfiesteria has been found

Public Interest Litigation and the Civil Society Factor

This article explores civil society organisations’ (CSOs) participation in judicial review proceedings. This became contentious when the Ministry of Justice announced that it intended to reform the judicial review process, and suggested changes to the law on standing and third party interventions (Ministry of Justice Judicial Review: Proposals for Further Reform London: TSO 2013, Cm 8703). Ultimately, the Criminal Justice and Courts Act 2015 did not amend the law in these areas, but has arguably made it more difficult for CSOs to engage in public interest litigation. Attempts to restrict the access of CSOs, to judicial review, need to be seen in the context of the shifting relationship between CSOs and the state, and differing perspectives on their function. If CSOs are to continue to take part in judicial review cases they need to justify their presence in terms of their expertise and on the ground knowledge. It is argued that deliberative, dignitarian, and more general theories about the nature of civil society may well establish a basis for CSOs’ continued presence in judicial review litigation

One-to-one support with a professional Rugby League Player: A case for referral?

This article presents a reflective case study of an applied consultancy experience with a 22-year-old professional rugby league player. The primary aim of the intervention was to provide the client a confidential space where he could discuss his experiences in and outside of a sporting context while also exploring and challenging his core values and beliefs. The consultancy process lasted for 12 mo, leading to the development of a strong relationship. During this time, the client experienced multiple critical moments such as deselection from the first-team squad and contract negotiations, which at times led to reductions in his well-being and forced the trainee sport and exercise psychologist to consider his scope of practice in relation to mental health and depression. Reflections are provided that explore the possibility of referral during these moments. The case study also provides insight into the trainee sport and exercise psychologist’s philosophy of practice and how influential this can be when considering referral of a client. The importance of supervisor support during uncertain moments is highlighted, and the case study concludes with reflections from the client, trainee practitioner, and peer supervisor regarding the efficacy of the intervention and the decision not to refer