Helen L. Parker

13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia

Historically, genes targeted by recurrent chromosomal deletions have been identified within the smallest genomic region shared in all patients, the minimally deleted region (MDR). However, deletions this small do not occur in all patients and are a simplification of the impact larger heterogeneous deletions have during carcinogenesis. We use the example of 13q14 deletions in chronic lymphocytic leukemia to show that genes outside MDRs are associated with disease progression. Genomic profiling of 224 patients identified 205 copy number alterations on chromosome 13 in 132 cases. Deletions including DLEU2 were heterogeneous (845u2009Kb–96.2u2009Mb) and identified two breakpoint cluster regions within short interspersed nuclear elements proximal to DLEU2 and within long interspersed nuclear elements/L1 repeats distal to GUCY1B2. After defining a deletion class on the basis of size and location, we show that (a) at diagnosis, larger deletions (class II) were associated with a significantly increased risk of disease progression (odds ratio=12.3; P=0.005), (b) in progressive patients, class II deletions were enriched (P=0.02) and (c) this association was independent of IgVH mutational status, ZAP70 expression and ATM/TP53 deletion. Deletion of a 1u2009Mb gene cluster (48.2–49.2u2009Mb), including SETDB2, PHF11 and RCBTB1, was significantly associated (P<0.01) with disease progression. Here, we show that the deletion of genes outside MDRs can influence clinical outcome.

The importance of being porous: polysaccharide-derived mesoporous materials for use in dye adsorption

The controlled pyrolysis of mesoporous polysaccharide-derived materials, from starch and alginic acid, formed carbonaceous materials (Starbons®) and were demonstrated as efficient materials for the removal of dyes from wastewater. The resulting materials were characterised by solid-state NMR, N2 adsorption porosimetry, FT-IR, scanning electron microscopy (SEM) and tunnelling electron microscopy (TEM). The material’s efficiency for dye adsorption was tested using methylene blue (MB) and acid blue 92 (AB) dyes. Adsorption data indicated that the mesoporosity of the material had a far greater influence on the adsorption capacity and speed of adsorption, than high surface area alone. Mesoporous Starbon® (A300) was evaluated against commercially available activated carbon (Norit) and demonstrated a superior adsorption capacity of MB; 186 mg g−1vs. 42 mg g−1. The kinetic activity of Starbon® was also determined with A800 showing the fastest rate of adsorption compared to S800 and Norit, suggesting that it is a more suitable material for water purification.

Applications of nanoparticles in biomass conversion to chemicals and fuels

Biorefineries are facilities that process biomass into fuels, power and value-added chemicals and with the increasing population and depleting petroleum reserves they are fast becoming more important to society. The technology required to process a wide variety of biomass types can be highly complex due to potentially unknown, varying or difficult to breakdown chemical structures within them. One of the prospective routes to a successful biorefinery, that can treat a wide range of biomass and produce products with good selectivity, is the use of nanoparticles as heterogeneous catalysts. The potential of nanoparticles to catalyse and modify chemical processes, thereby influencing both the nature of the products and their distribution is seen as highly promising. In this publication, we aim to give an overview of the use of a range of nano-catalysts and nano-enzymatic supports for greener biorefinery processing. Finally, future prospects of greener routes to nanoparticle production and their integration into biomass are discussed.

Supported palladium nanoparticles synthesized by living plants as a catalyst for Suzuki-Miyaura reactions.

The metal accumulating ability of plants has previously been used to capture metal contaminants from the environment; however, the full potential of this process is yet to be realized. Herein, the first use of living plants to recover palladium and produce catalytically active palladium nanoparticles is reported. This process eliminates the necessity for nanoparticle extraction from the plant and reduces the number of production steps compared to traditional catalyst palladium on carbon. These heterogeneous plant catalysts have demonstrated high catalytic activity in Suzuki coupling reactions between phenylboronic acid and a range of aryl halides containing iodo-, bromo- and chloro- moieties.

Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia

Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next-generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease.

Phytoextraction as a tool for green chemistry

Abstract The unique chemical and physical properties of metals mean that they are extensively utilized by industry in a huge variety of applications, including electronics, materials, industrial catalysts and chemicals. The increased consumer demand from a growing population worldwide with rising aspirations for a better life has resulted in concerns over the security of supply and accessibility of these valuable elements. As such, there is a growing need to develop alternative methods to recover them from waste repositories, current or historic, both for hazard avoidance and potentially, as a new source of metals for industry. Phytoextraction (the use of plants for the recovery of metals from waste repositories) is a green and novel technique for metal recovery, which, if done with the goal of resource supply rather than hazard mitigation, is termed “phytomining”. The ability for plants to form metallic nanoparticles as a consequence of phytoextraction could make the recovered metal ideally suited for utilization in green chemical technologies, such as catalysis. This review focuses on a multidisciplinary approach to elemental sustainability and highlights important aspects of metal lifecycle analysis, metal waste sources (including mine tailings), phytoextraction and potential green chemical applications that may result from the integration of these approaches.

Starch-derived carbonaceous mesoporous materials (Starbon®) for the selective adsorption and recovery of critical metals

The formation, characterization and application of starch-derived carbonaceous mesoporous materials (Starbon®) for the selective adsorption and recovery of critical metals (Au3+, Pt2+ and Pd2+) has been described. Starbon® successfully separated these critical metals from a mixture containing earth abundant elements (Ni2+, Cu2+ and Zn2+) with the consequent formation of metal nanoparticles.

Direct synthesis of Pd nanoparticles on alginic acid and seaweed supports

The direct synthesis of Pd catalysts using biosorption onto alginic acid and seaweed supports has been successfully achieved. The materials were carbonised to 300 °C and tested in C–C coupling reactions. The heating rate used during the stabilisation of the material had a direct effect on the activity of the catalyst with slower heating rates resulting in increased rates of reaction. Over 120 minutes the alginic acid catalysts achieved an 81% yield for the Heck reaction of iodobenzene with methyl acrylate. Both the seaweed and alginic acid catalysts were successfully reused 2 and 3 times respectively and demonstrated a significant improvement over Pd on carbon 1 wt% (Pd/C) which was not reusable. Overall, this work has shown that active nanoparticles of Pd could be produced using sustainable raw materials and green chemical processes. Such methods may open new doors for future metal capture and use.

Non-coding NOTCH1 mutations in chronic lymphocytic leukemia; their clinical impact in the UK CLL4 trial

Non-coding NOTCH1 mutations in chronic lymphocytic leukemia; their clinical impact in the UK CLL4 trial

Intelligent Approach to Solvent Substitution: The Identification of a New Class of Levoglucosenone Derivatives

With the increasing restriction and control of hazardous solvents, safer alternatives need to be identified. Here a contemporary approach to solvent selection and substitution is presented that offers a more scientific alternative to the simple like-for-like exchange. A new family of levoglucosenonederived compounds is proposed, modeled to determine their solvent properties, synthesized, and tested. These new molecules show promise as replacements for polar aprotic solvents that have chronic toxicity issues, such as dichloromethane, nitrobenzene, and N-methylpyrrolidinone. The success of this approach makes it possible for academia and industry to make calculated, intelligent choices for solvent substitution in the future.