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Refereed/Peer-reviewed Cutaneous melanoma is one of the most aggressive forms of skin cancer, with the development of advanced stage disease resulting in a high rate of patient mortality. Accurate diagnosis of melanoma at an early stage is essential to improve patient outcomes, as this enables treatment before the cancer has metastasised. Histopathologic analysis is the current gold standard for melanoma diagnosis, but this can be subjective due to discordance in interpreting the morphological heterogeneity in melanoma and other skin lesions. Immunohistochemistry (IHC) is sometimes employed as an adjunct to conventional histology, but it remains occasionally difficult to distinguish some benign melanocytic lesions and melanoma. Importantly, the complex morphology and lack of specific biomarkers that identify key elements of melanoma pathogenesis can make an accurate confirmation of diagnosis challenging. We review the diagnostic constraints of melanoma heterogeneity and discuss issues with interpreting routine histology and problems with current melanoma markers. Innovative approaches are required to find effective biomarkers to enhance patient management.

Tulsi (Holy basil, Ocimum tenuiflorum L., Lamiaceae), native to Asia, has become globalised as the cultural, cosmetic, and medicinal uses of the herb have been popularised. DNA barcoding, a molecular technique used to identify species based on short regions of DNA, can discriminate between different species and identify contaminants and adulterants. This study aimed to explore the values associated with Tulsi in the United Kingdom (UK) and authenticate samples using DNA barcoding. A mixed methods approach was used, incorporating social research (i.e., structured interviews) and DNA barcoding of Ocimum samples using the ITS and trnH-psbA barcode regions. Interviews revealed the cultural significance of Tulsi: including origins, knowledge exchange, religious connotations, and medicinal uses. With migration, sharing of plants and seeds has been seen as Tulsi plants are widely grown in South Asian (SA) households across the UK. Vouchered Ocimum specimens (n = 33) were obtained to create reference DNA barcodes which were not available in databases. A potential species substitution of O. gratissimum instead of O. tenuiflorum amongst SA participants was uncovered. Commercial samples (n = 47) were difficult to authenticate, potentially due to DNA degradation during manufacturing processes. This study highlights the cultural significance of Tulsi, despite a potential species substitution, the plant holds a prestigious place amongst SA families in the UK. DNA barcoding was a reliable way to authenticate Ocimum species.

Fluorescence microscopy has become a critical tool for researchers to understand biological processes at the cellular level. Micrographs from fixed and live-cell imaging procedures feature in a plethora of scientific articles for the field of cell biology, but the complexities of fluorescence microscopy as an imaging tool can sometimes be overlooked or misunderstood. This review seeks to cover the three fundamental considerations when designing fluorescence microscopy experiments: (1) hardware availability; (2) amenability of biological models to fluorescence microscopy; and (3) suitability of imaging agents for intended applications. This review will help equip the reader to make judicious decisions when designing fluorescence microscopy experiments that deliver high-resolution and informative images for cell biology. Refereed/Peer-reviewed

Microbially influenced concrete corrosion (MICC) in sewers is caused by the activity of sulfide-oxidizing microorganisms (SOMs) on concrete surfaces, which greatly deteriorates the integrity of sewers. Surface treatment of corroded concrete by spraying chemicals is a low-cost and non-intrusive strategy. This study systematically evaluated the spray of nitrite solution in corrosion mitigation and re-establishment in a real sewer manhole. Two types of concrete were exposed at three heights within the sewer manhole for 21 months. Nitrite spray was applied at the 6th month for half of the coupons which had developed active corrosion. The corrosion development was monitored by measuring the surface pH, corrosion product composition, sulfide uptake rate, concrete corrosion loss, and the microbial community on the corrosion layer. Free nitrous acid (FNA, i.e. HNO2), formed by spraying a nitrite solution on acidic corrosion surfaces, was shown to inhibit the activity of SOMs. The nitrite spray reduced the corrosion loss of concrete at all heights by 40–90% for six months. The sulfide uptake rate of sprayed coupons was also reduced by about 35%, leading to 1–2 units higher surface pH, comparing to the control coupons. The microbial community analysis revealed a reduced abundance of SOMs on nitrite sprayed coupons. The long-term monitoring also showed that the corrosion mitigation effect became negligible in 15 months after the spray. The results consistently demonstrated the effectiveness of nitrite spray on the MICC mitigation and identified the re-application frequencies for full scale applications.

The system constants of the solvation parameter model are used to prepare system maps for the retention of small neutral compounds on an octadecylsiloxane-bonded positive shield porous silica stationary phase (Luna Omega PS C18) for aqueous mobile phases containing 10–70% (v/v) methanol or acetonitrile. Electrostatic interactions (cation exchange) for weak bases were observed using acetonitrile–water but not methanol–water mobile phases at a similar level to a sterically shielded octadecylsiloxane-bonded silica column (Kinetex XB-C18). The system constants of the solvation parameter model and retention factor correlation plots for varied compounds indicated that the Luna Omega PS C18 stationary phase was (near) selectivity equivalent to the diisobutyloctadecylsiloxane-bonded superficially porous silica column Kinetex XB-C18. No specific interactions related to the embedded charged/chargeable functional group were observed compared with other high-purity type-B silica octadecylsiloxane-bonded stationary phases for typical reversed-phase separation conditions with unbuffered mobile phases.

Participatory research is an empowering process through which individuals can increase control over their lives, and allows researchers/clinicians to gain a clearer understanding of a child's needs. However, involving children in participatory research is still relatively novel, despite national and international mandates to engage children in decision making. This paper draws on the learnings from designing the Management and Intervention for Asthma (MIA) study, which used a collaborative participatory method to develop an intervention-planning framework for South Asian children with asthma. There are currently 1 million children in the UK receiving treatment for asthma, making it one of the most prevalent chronic childhood illnesses. Symptoms of asthma are often underrecognized in children from South Asian communities in the UK, contributing to increased disease severity and increased attendance at the emergency department compared to White British children. Despite this, ethnic minorities are often excluded from research and thus absent from the 'evidence base', making it essential to hear their perspectives if health inequalities are to be successfully addressed. We worked alongside healthcare professionals, community facilitators, parents, and children to identify the key concerns and priorities they had and then designed the framework around their needs. Reflecting on the process, we identified several key considerations that need to be addressed when co-developing interventions with children. These include the power dynamics between the parent/researcher and child; navigating the consent/assent process; how parental involvement might affect the research; establishing a convenient time and location; how to keep children engaged throughout the process; tailoring activities to different levels of ability; and accounting for cultural differences. These factors were considered by the researchers when designing the study, however, implementing them was not without its challenges and highlighted the need for researchers to develop expertise in this field. Tailoring existing research methods allowed us to explore children's perceptions, priorities, and experiences of illness more effectively. However, involving children in participatory research is a complex undertaking, and researchers need to ensure that they have the expertise, time, and resources necessary to be able to fully support the needs of child participants before deciding to commit to this approach.Involving families in health research gives children the opportunity to have more control over their healthcare and can help researchers/clinicians to better understand a child’s needs. However, involving children in research is still an uncommon practice despite international pressures to include children in decision making. This paper reflects on the development of the Management and Intervention for Asthma study, which worked with communities to develop a framework for planning health interventions for South Asian children with asthma. There are currently 1 million children in the UK being treated for asthma, making it one of the most common chronic childhood illnesses. Symptoms of asthma are overlooked in children from South Asian communities in the UK, leading to worse health outcomes and more visits to the emergency department. We worked with the community to identify the key concerns and priorities they had, and then jointly designed the framework around their needs. We identified several key things to consider when co-developing interventions with children: Power dynamics Consent/Assent Parental involvement Time and location Engagement Diversity of needs Ethnicity and Culture Adapting our research and engagement methods to suit children’s needs enabled us to involve them in the study in a way that allowed us to effectively explore their views, priorities, and experiences of their illness. However, researchers need to make sure that they have the expertise, time, and resources to be able to support the needs of child participants.

Space exploration poses multiple challenges for mankind, not only on a technical level but also to the entire physiology of the space traveller. The human system must adapt to several environmental stressors, microgravity being one of them. Lysosomes are ubiquitous to every cell and essential for their homeostasis, playing significant roles in the regulation of autophagy, immunity,and adaptation of the organism to changes in their environment, to name a few. Dysfunction of the lysosomal system leads to age-related diseases, for example bone loss, reduced immune response or cancer. As these conditions have been shown to be accelerated following exposure to microgravity,this review elucidates the lysosomal response to real and simulated microgravity. Microgravity activates the endo-lysosomal system, with resulting impacts on bone loss, muscle atrophy and stem cell differentiation. The investigation of lysosomal adaptation to microgravity can be beneficial in the search for new biomarkers or therapeutic approaches to several disease pathologies on earth as well as the potential to mitigate pathophysiology during spaceflight. Refereed/Peer-reviewed

Using micromagnetic simulations, we have modeled the formation of imprinted merons and antimerons in cobalt overlayers of different thickness (1--8 nm), stabilized by interfacial exchange with antiferromagnetic vortices in $\ensuremath{\alpha}\text{\ensuremath{-}}{\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$. Structures similar to those observed experimentally could be obtained with reasonable exchange parameters, also in the presence of surface roughness. We produce simulated meron and antimeron images by magnetic force microscopy and nitrogen-vacancy center microscopy, and established signatures of these topological structures in different experimental configurations.

We show that a polar, pseudo-Jahn-Teller instability exists for the underbonded rare-earth A-site cations in the quadruple perovskite Dy_{1-δ}Mn_{7+δ}O_{12}, which leads to the spontaneous formation of a dipolar glass. This observation alone expands the applicability of pseudo-Jahn-Teller physics in perovskite-derived materials, for which it is typically confined to B-site cations. We demonstrate that the dipolar glass order parameter is coupled to a ferrimagnetic order parameter via strain, leading to a first order magnetostructural phase transition that can be tuned by magnetic field. This phenomenology may emerge in a broad range of perovskite-derived materials in which A-site cation ordering and octahedral tilting are mutually tied to meet the criteria of structural stability.

Spin-reorientation phase transitions that involve the rotation of a crystal$'$s magnetization have been well characterized in distorted-perovskite oxides such as the orthoferrites. In these systems spin reorientation occurs due to competing rare-earth and transition metal anisotropies coupled via $f$-$d$ exchange. Here, we demonstrate an alternative paradigm for spin reorientation in distorted perovskites. We show that the $R_2\mathrm{CuMnMn_4O_{12}}$ (R = Y or Dy) triple A-site columnar-ordered quadruple perovskites have three ordered magnetic phases and up to two spin-reorientation phase transitions. Unlike the spin-reorientation phenomena in other distorted perovskites, these transitions are independent of rare-earth magnetism, but are instead driven by an instability towards antiferromagnetic spin canting likely originating in frustrated Heisenberg exchange interactions, and the competition between Dzyaloshinskii-Moriya and single-ion anisotropies., 5 pages, 3 figures

Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three approaches identified significant difference in the lipid profiles of the three prostate cancer cell lines (DU145, LNCaP and 22RV1) and one non-malignant cell line (PNT1a). Specific lipid classes and species, such as phospholipids (e.g., phosphatidylethanolamine 18:1/16:0 and 18:1/18:1) and cholesteryl esters, detected by LC-ESI-MS/MS, allowed statistical separation of all four prostate cell lines. Lipid mapping by FTIR revealed that variations in these lipid classes could also be detected at a single cell level, however further investigation into this approach would be needed to generate large enough data sets for quantitation. Visualisation by fluorescence microscopy showed striking variations that could be observed in lipid staining patterns between cell lines allowing visual separation of cell lines. In particular, polar lipid staining by a fluorescent marker was observed to increase significantly in prostate cancer lines cells, when compared to PNT1a cells, which was consistent with lipid quantitation by LC-ESI-MS/MS and FTIR spectroscopy. Thus, multiple technologies can be employed to either quantify or visualise changes in lipid composition, and moreover specific lipid profiles could be used to detect and phenotype prostate cancer cells Refereed/Peer-reviewed

Reactive oxygen species ( ROS ) promote growth factor signalling including for VEGF - A and have potent angiogenic and tumourigenic properties . However, the precise enzymatic source of ROS generation, the subcellular localization of ROS production and cellular targets in vivo that influence tumour - promoting processes , are largely undefined . Here , using mRNA microarrays, we show increased gene expression for NOX2 , the catalytic subunit of the ROS - generating NADPH oxidase enzyme , in human primary prostate cancer compared to non - malignant tissue. In addition , NOX4 gene expression was markedly elevated in human metastatic prostate cancers , but not in primary prostate tumours . Using a syngeneic, orthotopic mouse model of prostate cancer the genetic deletion of NOX2 (i.e. NOX2-/y mouse) resulted in reduced angiogenesis and an almost complete failure in tumour development. Furthermore, pharmacological inhibition of NOX2 oxidase suppressed established prostate tumours in mice. In isolated endothelial cells, and in human normal and prostate cancer cells, NOX2 co - located to varying degrees with early endosome markers including EEA1, Appl1 and Rab5 A and the late endosome marker Rab7A, and this correlated with significant VEGF - A - dependent ROS production within acidified endosomal compartments and endothelial cell proliferation that was NOX2 oxidase - and hydrogen peroxide dependent. We concluded that NOX2 oxidase expression and endosomal ROS production were important for prostate cancer growth and that this was required to positively regulate the VEGF pathway . The research provides a paradigm for limiting tumour growth through a better understanding of NOX2 oxidase's effect on VEGF signalling and how controlling the development of tumour vasculature can limit prostate tumour development and metastasis.

The molecular chaperone Hsp90 is overexpressed in prostate cancer (PCa) and is responsible for the folding, stabilization and maturation of multiple oncoproteins, which are implicated in PCa progression. Compared to first-in-class Hsp90 inhibitors such as 17-allylamino-demethoxygeldanamycin (17-AAG) that were clinically ineffective, second generation inhibitor AUY922 has greater solubility and efficacy. Here, transcriptomic and proteomic analyses of patient-derived PCa explants identified cytoskeletal organization as highly enriched with AUY922 treatment. Validation in PCa cell lines revealed that AUY922 caused marked alterations to cell morphology, and suppressed cell motility and invasion compared to vehicle or 17-AAG, concomitant with dysregulation of key extracellular matrix proteins such as fibronectin (FN1). Interestingly, while the expression of FN1 was increased by AUY922, FN1 secretion was significantly decreased. This resulted in cytosolic accumulation of FN1 protein within late endosomes, suggesting that AUY922 disrupts vesicular secretory trafficking pathways. Depletion of FN1 by siRNA knockdown markedly reduced the invasive capacity of PCa cells, phenocopying AUY922. These results highlight a novel mechanism of action for AUY922 beyond its established effects on cellular mitosis and survival and, furthermore, identifies extracellular matrix cargo delivery as a potential therapeutic target for the treatment of aggressive PCa.

Microbially induced concrete corrosion is a major deterioration process in sewers, causing a huge economic burden, and improved mitigating technologies are required. This study reports a novel and promising effective solution to attenuate the corrosion in sewers using calcium nitrite-admixed concrete. This strategy aims to suppress the development and activity of corrosion-inducing microorganisms with the antimicrobial free nitrous acid, which is generated in situ from calcium nitrite that is added to the concrete. Concrete coupons with calcium nitrite as an admixture were exposed in a sewer manhole, together with control coupons that had no nitrite admixture, for 18 months. The corrosion process was monitored by measuring the surface pH, corrosion product composition, concrete corrosion loss, and the microbial community on the corrosion layer. During the exposure, the corrosion loss of the admixed concrete coupons was 30% lower than that of the control coupons. The sulfide uptake rate of the admixed concrete was also 30% lower, leading to a higher surface pH (0.5-0.6 unit), in comparison to that of the control coupons. A negative correlation between the calcium nitrite admixture in concrete and the abundance of sulfide-oxidizing microorganisms was determined by DNA sequencing. The results obtained in this field study demonstrated that this novel use of calcium nitrite as an admixture in concrete is a promising strategy to mitigate the microbially induced corrosion in sewers.

Additional file 1 : Table SM1. Unadjusted odds ratios (OR) with 99% Confidence Intervals (CIs) for all measures in relation to being in the cohort over the comparison group.

${\mathrm{Ba}}_{3}{\mathrm{NbFe}}_{3}{\mathrm{Si}}_{2}{\mathrm{O}}_{14}$ (langasite) is structurally and magnetically single-domain chiral with the magnetic helicity induced through competing symmetric exchange interactions. Using neutron scattering, we show that the spin waves in antiferromagnetic langasite display directional anisotropy. On applying a time-reversal symmetry breaking magnetic field along the $c$ axis, the spin-wave energies differ when the sign is reversed for either the momentum transfer $\ifmmode\pm\else\textpm\fi{}\stackrel{P\vec}{Q}$ or applied magnetic field $\ifmmode\pm\else\textpm\fi{}{\ensuremath{\mu}}_{0}\mathrm{H}$. When the field is applied within the crystallographic $ab$ plane, the spin-wave dispersion is directionally isotropic and symmetric in $\ifmmode\pm\else\textpm\fi{}{\ensuremath{\mu}}_{0}\mathrm{H}$. However, a directional anisotropy is observed in the spin-wave intensity. We discuss this directional anisotropy in the dispersion in langasite in terms of a field-induced precession of the dynamic unit cell staggered magnetization resulting from a broken twofold symmetry. Directional anisotropy, often referred to as nonreciprocal responses, can occur in antiferromagnetic phases in the absence of the Dzyaloshinskii-Moriya interaction or other effects resulting from spin-orbit coupling.

Pesticide residue analysis in cannabis has become a subject of growing interest in North America since recent legalization in Canada and decriminalization for medicinal or recreational use in most US states. To meet regulatory and quality control standards, cannabis products should be tested for both authorized and unauthorized pesticides. In Canada, testing requirements mandated by Health Canada stipulate pesticide contaminant limits of quantification values of 0.02–3.0 μg/g, 0.01–2.5 μg/g and 0.01–1.5 μg/g for cannabis dried flowers, oil and fresh plants, respectively. Sample preparation and clean up methods reported in the literature for pesticide analysis in cannabis products include liquid-liquid extraction, solid-phase extraction, solid-phase microextraction and QuEChERS whereas separation and detection methods include thin-layer chromatography, capillary electrophoresis, high-performance liquid chromatography and gas chromatography in combination with various detectors such as UV and mass spectrometers. Advantages and disadvantages of the various analytical methods used in pesticide analysis of cannabis products are evaluated in this review. Furthermore, challenges ahead and future directions are discussed.

In recent years G protein-coupled receptors (GPCRs) have emerged as crucial tumorigenic factors that drive aberrant cancer growth, metastasis and angiogenesis. Consequently, a number of GPCRs are strongly expressed in cancer derived cell lines and tissue samples. Therefore a rational anti-cancer strategy is the design of nano-medicines that specifically target GPCRs to bind and internalise cytotoxic drugs into cancer cells. Herein, we report the genetic engineering of a self-assembling nanoparticle based on elastin-like polypeptide (ELP), which has been fused with gastrin releasing peptide (GRP). These nanoparticles increased intracellular calcium concentrations when added to GRP receptor positive PC-3 prostate cancer cells, demonstrating specific receptor activation. Moreover, GRP-displaying fluorescent labelled nanoparticles showed specific cell-surface interaction with PC-3 prostate cancer cells and increased endocytic uptake. These nanoparticles therefore provide a targeted molecular carrier system for evaluating the delivery of cytotoxic drugs into cancer cells. Refereed/Peer-reviewed

The synthesis and reactivity of two new bis(phosphinimine)carbazole ligands (PippN=PMe2)2DMC (HLA, 3) and (PippN=P(C4H8))2DMC (HLB, 10), where Pipp = para-isopropylphenyl and DMC = 3,6-dimethylcarbazole, are reported. Dialkyl lutetium complexes of 3 and 10 were prepared in the presence of DMAP and THF by reaction of the proteo ligands with the new trialkyl reagent, Lu(CH2SiMe3)3(DMAP)2 (4) as well as Lu(CH2SiMe3)3(THF)2. For both ligands 3 and 10, the resulting lutetium complexes were prone to intramolecular cyclometalative alkane elimination reactions whereby the location of cyclometalation was influenced by the identity of the ancillary ligand coordinated to the metal. For ligand 3, cyclometalation of two PMe2 groups generated the complex (LA-κ3N,κ2C)Lu(DMAP)2 (5), whereas ligand 10 resulted in the single ortho-metalation of a para-isopropylphenyl ring to afford (LB-κ3N,κC)Lu(CH2SiMe3) (12). When complexed with scandium, ligand 10 behaved differently; double cyclometalation of two phospholane moieties resulted in the species (LB-κ3N,κ2C)Sc (15). The nature of the cyclometalation reactivity of ligands 3 and 10 is supported by X-ray crystallography and kinetic analysis, respectively.

The synthesis of scandium complexes supported by two bis(trimethylsilyl)amido ligands and their reactivity to generate a variety of organometallic derivatives is reported. The monomeric scandium complex Sc{N(SiMe3)2}2(THF)Cl, 1, and the “ate” complex Sc{N(SiMe3)2}2Cl2Li(THF)3, 2, were generated by salt metathesis routes from ScCl3(THF)3 and LiN(SiMe3)2. Complex 1 reacts cleanly with MeLi or KCH2Ph to form the compounds Sc{N(SiMe3)2}2(THF)R, (R = Me, 3; CH2Ph, 4), respectively. Upon reaction of 1 with bulky lithium reagents such as LiCH2SiMe3 or TripLi, cyclometalation at scandium occurs to generate the bimetallic species Sc{N(SiMe3)2}2(μ-CH2)2Sc{N(SiMe3)SiMe2}2(THF), 5. Finally, the scandium iodide congener Sc{N(SiMe3)2}2(THF)I, 6, was produced by reaction of 3 with the iodide transfer reagent [Et3NH]I. Attempts to access a low valent scandium complex, by reduction of 6 with either KC8 or [(nacnac)Mg]2, where nacnac = (2,6-iPr2-C6H3)NC(Me)CHC(Me)N(2,6-iPr2-C6H3) failed to afford well-defined low valent organometallic scandium species. All compounds were characterized by single crystal X-ray diffraction studies.

The presence of domains in ferroic materials can negatively affect their macroscopic properties and hence their usefulness in device applications. From an experimental perspective, the measurement of materials comprising multiple domains can complicate the interpretation of the material properties and their underlying mechanisms. In general, BiFeO3 films tend to grow with multiple magnetic domains and often contain multiple ferroelectric- and ferroelastic-domain variants. By growing (111)-oriented BiFeO3 films on an orthorhombic TbScO3 substrate, we are able to overcome this and, by exploiting the magnetoelastic coupling between the magnetic and crystal structures, bias the growth of a given magnetic-, ferroelectric-, and structural-domain film. We further demonstrate the coupling of the magnetic structure to the ferroelectric polarization by showing that the magnetic polarity in this domain is inverted upon 180∘ ferroelectric switching.

Epichloë festucae fungi form bioprotective endophytic symbioses with perennial ryegrass. Although this interaction is economically important, relatively little is known about the molecular processes and regulatory genes that are involved in establishing a compatible symbiosis. The present study utilised next-generation sequencing to investigate the genes required for establishing a compatible symbiotic interaction between E. festucae and perennial ryegrass. A comparative transcriptomics study, comparing the compatible symbiotic interaction of E. festucae/perennial ryegrass with the incompatible interaction of a ΔlaeA mutant strain of E.festucae/perennial ryegrass, was performed two weeks after inoculation. Differentially expressed genes were identified and classified according to gene ontology and functional annotation analyses. The raw data of this study have been deposited at SRA database with the BioProject ID PRJNA513830.

By employing resonant X-ray microdiffraction, we image the magnetisation and magnetic polarity domains of the Y-type hexaferrite Ba$_{0.5}$Sr$_{1.5}$Mg$_2$Fe$_{12}$O$_{22}$. We show that the magnetic polarity domain structure can be controlled by both magnetic and electric fields, and that full inversion of these domains can be achieved simply by reversal of an applied magnetic field in the absence of an electric field bias. Furthermore, we demonstrate that the diffraction intensity measured in different X-ray polarisation channels cannot be reproduced by the accepted model for the polar magnetic structure, known as the 2-fan transverse conical (TC) model. We propose a modification to this model, which achieves good quantitative agreement with all of our data. We show that the deviations from the TC model are large, and may be the result of an internal magnetic chirality, most likely inherited from the parent helical (non-polar) phase., Comment: 9 figures

We report a neutron powder diffraction study of $R{\mathrm{Mn}}_{7}{\mathrm{O}}_{12}$ quadruple perovskite manganites with $R=\mathrm{La}$, Ce, Nd, Sm, and Eu. We show that in all measured compounds concomitant magnetic ordering of the $A$ and $B$ manganese sublattices occurs on cooling below the N\'eel temperature. The respective magnetic structures are collinear, with one uncompensated ${\mathrm{Mn}}^{3+}$ moment per formula unit as observed in bulk magnetization measurements. We show that both ${\mathrm{LaMn}}_{7}{\mathrm{O}}_{12}$ and ${\mathrm{NdMn}}_{7}{\mathrm{O}}_{12}$ undergo a second magnetic phase transition at low temperature, which introduces a canting of the $B$-site sublattice moments that is commensurate in ${\mathrm{LaMn}}_{7}{\mathrm{O}}_{12}$ and incommensurate in ${\mathrm{NdMn}}_{7}{\mathrm{O}}_{12}$. This spin canting is consistent with a magnetic instability originating in the $B$-site orbital order. Furthermore, ${\mathrm{NdMn}}_{7}{\mathrm{O}}_{12}$ displays a third magnetic phase transition at which long-range ordering of the Nd sublattice modifies the periodicity of the incommensurate spin canting. Our results demonstrate a rich interplay between transition-metal magnetism, orbital order, and the crystal lattice, which may be fine-tuned by cation substitution and rare-earth magnetism.

We investigate the low-temperature magnetic properties of the molecule-based chiral spin chain [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O (pym=pyrimidine). Electron-spin resonance, magnetometry and heat capacity measurements reveal the presence of staggered g tensors, a rich low-temperature excitation spectrum, a staggered susceptibility, and a spin gap that opens on the application of a magnetic field. These phenomena are reminiscent of those previously observed in nonchiral staggered chains, which are explicable within the sine-Gordon quantum-field theory. In the present case, however, although the sine-Gordon model accounts well for the form of the temperature dependence of the heat capacity, the size of the gap and its measured linear field dependence do not fit with the sine-Gordon theory as it stands. We propose that the differences arise due to additional terms in the Hamiltonian resulting from the chiral structure of [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O, particularly a uniform Dzyaloshinskii-Moriya coupling and a fourfold periodic staggered field.

We present the discovery and refinement by neutron powder diffraction of a new magnetic phase in the Na_{1-x}Ca_{x}Mn_{7}O_{12} quadruple perovskite phase diagram, which is the incommensurate analogue of the well-known pseudo-CE phase of the simple perovskite manganites. We demonstrate that incommensurate magnetic order arises in quadruple perovskites due to the exchange interactions between A and B sites. Furthermore, by constructing a simple mean field Heisenberg exchange model that generically describes both simple and quadruple perovskite systems, we show that this new magnetic phase unifies a picture of the interplay between charge, magnetic, and orbital ordering across a wide range of compounds.

We present the discovery and refinement by neutron powder diffraction of a new magnetic phase in the Na_{1-x}Ca_{x}Mn_{7}O_{12} quadruple perovskite phase diagram, which is the incommensurate analogue of the well-known pseudo-CE phase of the simple perovskite manganites. We demonstrate that incommensurate magnetic order arises in quadruple perovskites due to the exchange interactions between A and B sites. Furthermore, by constructing a simple mean field Heisenberg exchange model that generically describes both simple and quadruple perovskite systems, we show that this new magnetic phase unifies a picture of the interplay between charge, magnetic, and orbital ordering across a wide range of compounds.

Refereed/Peer-reviewed

Autophagy is an intracellular recycling and degradation process, which is important for energy metabolism, lipid metabolism, physiological stress response and organism development. During Drosophila development, autophagy is up-regulated in fat body and midgut cells, to control metabolic function and to enable tissue remodelling. Atg9 is the only transmembrane protein involved in the core autophagy machinery and is thought to have a role in autophagosome formation. During Drosophila development, Atg9 co-located with Atg8 autophagosomes, Rab11 endosomes and Lamp1 endosomes-lysosomes. RNAi silencing of Atg9 reduced both the number and the size of autophagosomes during development and caused morphological changes to amphisomes/autolysosomes. In control cells there was compartmentalised acidification corresponding to intraluminal Rab11/Lamp-1 vesicles, but in Atg9 depleted cells there were no intraluminal vesicles and the acidification was not compartmentalised. We concluded that Atg9 is required to form intraluminal vesicles and for localised acidification within amphisomes/autolysosomes, and consequently when depleted, reduced the capacity to degrade and remodel gut tissue during development., Summary: The disappearance of intraluminal vesicles in amphisomes/autolysosomes upon Atg9 depletion suggests that Atg9 has a specific role in intraluminal vesicle formation in autophagic compartments.

Mitochondrial morphology is important for the function of this critical organelle and, accordingly, altered mitochondrial structure is exhibited in many pathologies. Imaging of mitochondria can therefore provide important information about disease presence and progression. However, mitochondrial imaging is currently limited by the availability of agents that have the capacity to image mitochondrial morphology in both live and fixed samples. This can be particularly problematic in clinical studies or large, multi-centre cohort studies, where tissue archiving by fixation is often more practical. We previously reported the synthesis of an iridium coordination complex [Ir(ppy)2(MeTzPyPhCN)]+; where ppy is a cyclometalated 2-phenylpyridine and TzPyPhCN is the 5-(5-(4-cyanophen-1-yl)pyrid-2-yl)tetrazolate ligand; and showed that this complex (herein referred to as IraZolve-Mito) has a high specificity for mitochondria in live cells. Here we demonstrate that IraZolve-Mito can also effectively stain mitochondria in both live and fixed tissue samples. The staining protocol proposed is versatile, providing a universal procedure for cell biologists and pathologists to visualise mitochondria.

We have directly imaged reversible electrical switching of the cycloidal rotation direction (magnetic polarity) in a (111)pc-BiFeO3 epitaxial-film device at room temperature by non-resonant x-ray magnetic scattering. Consistent with previous reports, fully relaxed (111)pc-BiFeO3 epitaxial films consisting of a single ferroelectric domain were found to comprise a sub-micron-scale mosaic of magneto-elastic domains, all sharing a common direction of the magnetic polarity, which was found to switch reversibly upon reversal of the ferroelectric polarization without any measurable change of the magneto-elastic domain population. A real-space polarimetry map of our device clearly distinguished between regions of the sample electrically addressed into the two magnetic states with a resolution of a few tens of micron. Contrary to the general belief that the magneto-electric coupling in BiFeO3 is weak, we find that electrical switching has a dramatic effect on the magnetic structure, with the magnetic moments rotating on average by 90 degrees at every cycle.

The synthesis and reactivity of a bulky bis(phosphinimine)carbazole pincer ligand (HL) bearing mesityl N-aryl groups is described. Reaction of HL with Y(CH2SiMe3)3(THF)2 afforded a doubly cyclometalated organoyttrium complex, whereby the ligand was κ3N, κ2C coordinated to the metal via three nitrogen atoms and two ortho-metalated P-phenyl rings. Deprotonation of (HL) with nBuLi liberated a monomeric and thermally stable lithium salt of the ligand (LLi). Salt metathesis reactions of LLi with ScCl3(THF)3 and YCl3(THF)3.5 generated the corresponding rare earth dichloro complexes, which were found to be monomeric and Lewis-base free.

Two derivatives of a new bis(pyrazolyl)carbazole pincer ligand H(CzPzR), R = iPr and Me, and their syntheses are reported. Lutetium dialkyl complexes of the ligand (CzPzR)Lu(CH2SiMe3)2, R = iPr and...

Hydrogen sulfide induced corrosion of concrete sewer pipes is a major issue for wastewater utilities globally. One of the most commonly used methods to combat hydrogen sulfide is the addition of ferric chloride. While a reliable and effective method, ferric chloride is acidic causing OH&S concerns as well as alkalinity consumption in sewage. This study investigates, under full-scale field conditions, an alternative method for sulfide control by in-situ electrochemical generation of iron ions using sacrificial iron electrodes. This method concomitantly produces alkalinity through cathodic OH− generation, rather than consumption. The gaseous hydrogen sulfide concentrations at the discharge wet well of a real-life rising main (length: ∼1 km in, diameter: 150 mm) decreased from 173 ppm to 43 ppm (90 percentile of peak values), when a current of 0.86 A/m3 of sewage was applied. The 90 percentile peak H2S value was further reduced to 6.6 ppm when the applied current was increased to 1.14 A/m3 sewage. Moreover, methane generation was almost completely inhibited from 25.3 ± 1.46 mg COD/L to 0.06 ± 0.04 mg COD/L. The overall cell voltage remained constant throughout the experimental period clearly showing the stability of the process. Detailed characterization of the down-stream sewer pipe biofilm revealed the complexity of the iron chemistry as the in-situ produced iron ions undergo transformation into a variety of iron species. Overall, this study demonstrates that in-situ generation of iron and alkalinity is an effective alternative method for hydrogen sulfide control in sewers.

Syntenin-1 is an essential multi-functional adaptor protein, which has multiple roles in membrane trafficking and exosome biogenesis, as well as scaffolding interactions with either the actin cytoskeleton or focal adhesions. However, how this functional multiplicity relates to syntenin-1 distribution in different endosome compartments or other intracellular locations and its underlying involvement in cancer pathogenesis have yet to be fully defined. To help facilitate the investigation of syntenin-1 biology, we developed two specific monoclonal antibodies (Synt-2C6 and Synt-3A11) to spatially distinct linear sequence epitopes on syntenin-1, which were each designed to be unique at the six-amino acid level. These antibodies produced very different intracellular staining patterns, with Synt-2C6 detecting endosomes and Synt-3A11 producing a fibrillar staining pattern suggesting a cytoskeletal localisation. Treatment of cells with Nocodazole altered the intracellular localisation of Synt-3A11, which was consistent with the syntenin-1 protein interacting with microtubules. In prostate tissue biopsies, Synt-3A11 defined atrophy and early-stage prostate cancer, whereas Synt-2C6 only showed minimal interaction with atrophic tissue. This highlights a critical need for site-specific antibodies and a knowledge of their reactivity to define differential protein distributions, interactions and functions, which may differ between normal and malignant cells. Refereed/Peer-reviewed

BACKGROUND Prostate cancer cell lines have been used in the search for biomarkers that are suitable for prostate cancer diagnosis. Unfortunately, many cell line studies have only involved single cell lines, partially characterized cell lines or were performed without controls, and this may have been detrimental to effective biomarker discovery. We have analyzed a panel of prostate cancer and nonmalignant control cell lines using current biomarkers and then investigated a set of prospective endosomal and lysosomal proteins to search for new biomarkers. METHODS Western blotting was used to define the amount of protein and specific molecular forms in cell extracts and culture media from a panel of nonmalignant (RWPE-1, PNT1a, PNT2) and prostate cancer (22RV1, CaHPV10, DU-145, LNCaP) cell lines. Gene expression was determined by qRT-PCR. RESULTS HPV-18 transfected cell lines displayed a different pattern of protein and gene expression when compared to the other cell lines examined, suggesting that these cell lines may not be the most optimal for prostate cancer biomarker discovery. There was an increased amount of prostatic acid phosphatase and kallikrein proteins in LNCaP cell extracts and culture media, but variable amounts of these proteins in other prostate cancer cell lines. There were minimal differences in the amounts of lysosomal proteins detected in prostate cancer cells and culture media, but two endosomal proteins, cathepsin B and acid ceramidase, had increased gene and protein expression, and certain molecular forms showed increased secretion from prostate cancer cells (P ≤ 0.05). LIMP-2 gene and protein expression was significantly increased in prostate cancer compared to nonmalignant cell lines (P ≤ 0.05). CONCLUSIONS While the existing prostate cancer biomarkers and lysosomal proteins investigated here were not able to specifically differentiate between a panel of nonmalignant and prostate cancer cell lines, endosomal proteins showed some discriminatory capacity. LIMP-2 is a critical regulator of endosome biogenesis and the increased expression observed in prostate cancer cells indicated that other endosome related proteins may also be upregulated and could be investigated as novel biomarkers. Prostate 74:547–560, 2014. © 2014 Wiley Periodicals, Inc.

The synthesis of a pentadentate NNNNN bis(phosphinimine)carbazole pincer ligand bearing two pyrimidine N-aryl rings is reported. A dialkyl lutetium complex of the ligand, prepared by alkane elimination with Lu(CH2SiMe3)3(THF)2, was found to undergo an unusual transformation involving a double alkyl shift whereby the −CH2SiMe3 groups on the metal migrated to both pyrimidine rings. This migration afforded a final product that featured alkyl-functionalized, dearomatized ligand pyrimidine rings.