Single-enzyme biomineralization of cadmium sulfide nanocrystals with controlled optical properties

Nature has evolved several unique biomineralization strategies to direct the synthesis and growth of inorganic materials. These natural systems are complex, involving the interaction of multiple biomolecules to catalyze biomineralization and template growth. Herein we describe the first report to our knowledge of a single enzyme capable of both catalyzing mineralization in otherwise unreactive solution and of templating nanocrystal growth. A recombinant putative cystathionine γ-lyase (smCSE) mineralizes CdS from an aqueous cadmium acetate solution via reactive H2S generation from l-cysteine and controls nanocrystal growth within the quantum confined size range. The role of enzymatic nanocrystal templating is demonstrated by substituting reactive Na2S as the sulfur source. Whereas bulk CdS is formed in the absence of the enzyme or other capping agents, nanocrystal formation is observed when smCSE is present to control the growth. This dual-function, single-enzyme, aerobic, and aqueous route to functional material synthesis demonstrates the powerful potential of engineered functional material biomineralization

Single enzyme direct biomineralization of ZnS, ZnxCd1�xS and ZnxCd1�xS–ZnS quantum confined nanocrystals

ZnS, ZnxCd1−xS, and ZnxCd1−xS–ZnS quantum dots were synthesized in the aqueous phase at room temperature via biomineralization enabled by a single enzyme in solution.</p

Biomineralized CdS quantum dot nanocrystals: optimizing synthesis conditions and improving functional properties by surface modification

An engineered strain of Stenotrophomonas maltophilia (SMCD1) is capable of the direct extracellular biomineralization of CdS quantum dot nanocrystals from buffered aqueous solution of cadmium acetate and l-cysteine without the addition of a chemically reactive precursor. Nanocrystal synthesis is strongly influenced by both the l-cysteine/cadmium acetate ratio and pH of the solution. The observed trends are consistent with l-cysteine acting as both a sulfur source and nanocrystal capping agent. Enzymatic turnover of l-cysteine by a putative cystathionine γ-lyase forms reactive sulfur in solution, removing the requirement for addition of reactive sodium sulfide typical of most other biomineralization approaches. The utility of the biomineralized quantum dots is demonstrated by phase transfer from the aqueous to the organic phase and subsequent incorporation into a quantum dot sensitized solar cell and chemical growth of a ZnS shell onto the biomineralized CdS core

Single enzyme direct biomineralization of CdSe and CdSe-CdS core-shell quantum dots

Biomineralization is the process by which biological systems synthesize inorganic materials. Herein, we demonstrate an engineered cystathionine γ-lyase enzyme, smCSE that is active for the direct aqueous phase biomineralization of CdSe and CdSe-CdS core-shell nanocrystals. The nanocrystals are formed in an otherwise unreactive buffered solution of Cd acetate and selenocystine through enzymatic turnover of the selenocystine to form a reactive precursor, likely H2Se. The particle size of the CdSe core nanocrystals can be tuned by varying the incubation time to generated particle sizes between 2.74 ± 0.63 nm and 4.78 ± 1.16 nm formed after 20 min and 24 h of incubation, respectively. Subsequent purification and introduction of l-cysteine as a sulfur source facilitates the biomineralization of a CdS shell onto the CdSe cores. The quantum yield of the resulting CdSe-CdS core-shell particles is up to 12% in the aqueous phase; comparable to that reported for more traditional chemical synthesis routes for core-shell particles of similar size with similar shell coverage. This single-enzyme route to functional nanocrystals synthesis reveals the powerful potential of biomineralization processes

Biomineralization of PbS and PbS-CdS core-shell nanocrystals and their application in quantum dot sensitized solar cells

Biomineralization utilizes biological systems to synthesize functional inorganic materials for application in diverse fields. In the current work, we enable biomineralization of quantum confined PbS and PbS–CdS core–shell nanocrystals and demonstrate their application in quantum dot sensitized solar cells (QDSSCs). An engineered strain of Stenotrophomonas maltophilia is utilized to generate a cystathionine γ-lyase that is active for the biomineralization of metal sulfide nanocrystals from a buffered aqueous solution of metal salts and L-cysteine. In the presence of lead acetate, this enzymatic route generates rock salt structured PbS nanocrystals. Controlling the growth conditions yields ∼4 nm PbS crystals with absorption and photoluminescence peaks at 910 nm and 1080 nm, respectively, consistent with the expected strong quantum confinement of PbS at this size. Quantum yields (QY) of the biomineralized PbS quantum dots, determined after phase transfer to the organic phase, range between 16 and 45%. These are the highest reported QY values for any biomineralized quantum dot materials to date and are comparable with QYs reported for chemically synthesized materials. Subsequent exposure to cadmium acetate results in the biomineralization of a thin CdS shell on the PbS core with a resultant blue-shift in optical properties. The photoluminescence peak shifts to 980 nm, consistent with the expected decrease in band gap energy of a PbS–CdS core–shell heterostructured quantum dot. HAADF-STEM imaging confirms the crystalline structure and size of the particles with complimentary XEDS analysis confirming the presence of Cd, Pb, and S in individual nanocrystals. Integration of these QDs into QDSSCs yields open circuit potentials of 0.43 V and 0.59 V for PbS and PbS–CdS, respectively, consistent with expectations for these materials and previously reported values for chemically synthesized QDs

Enzymatic biomineralization of biocompatible CuInS2, (CuInZn)S2 and CuInS2/ZnS core/shell nanocrystals for bioimaging

This work demonstrates a bioenabled, aqueous phase, room temperature route to synthesize CuInS2/ZnS quantum dots conjugated to IgG antibodies for fluorescent tagging of THP-1 leukemia cells.</p

Structural Basis for α-Conotoxin Potency and Selectivity

Parkinson\u27s disease is a debilitating movement disorder characterized by altered levels of α6β2* nicotinic acetylcholine receptors (nAChRs) localized on presynaptic striatal catecholaminergic neurons. α-Conotoxin MII (α-CTx MII) is a highly useful ligand to probe α6ß2 nAChRs structure and function, but it does not discriminate among closely related α6* nAChR subtypes. Modification of the α-CTx MII primary sequence led to the identification of α-CTx MII[E11A], an analog with 500-5300 fold discrimination between α6* subtypes found in both human and non-human primates. α-CTx MII[E11A] binds most strongly (femtomolar dissociation constant) to the high affinity α6* nAChR, a subtype that is selectively lost in Parkinson\u27s disease. Here we present the three-dimensional solution structure for α-CTx MII[E11A] as determined by two-dimensional 1H NMR spectroscopy to 0.13 +/- 0.09 Ǻ backbone and 0.45 +/- 0.08 Ǻ heavy atom root mean square deviation from mean structure. Structural comparisons suggest that the increased hydrophobic area of α-CTx MII[E11A] relative to other members of the α-CTx family may be responsible for its exceptionally high affinity for α6α4β2* nAChR as well as discrimination between α6ß2 and α3β2 containing nAChRs. This finding may enable the rational design of novel peptide analogs that demonstrate enhanced specificity for α6* nAChR subunit interfaces and provide a means to better understand nAChR structural determinants that modulate brain dopamine levels and the pathophysiology of Parkinson\u27s disease

Direct single-enzyme biomineralization of catalytically active ceria and ceria-zirconia nanocrystals

Biomineralization is an intriguing approach to the synthesis of functional inorganic materials for energy applications whereby biological systems are engineered to mineralize inorganic materials and control their structure over multiple length scales under mild reaction conditions. Herein we demonstrate a single-enzyme-mediated biomineralization route to synthesize crystalline, catalytically active, quantum-confined ceria (CeO2–x) and ceria–zirconia (Ce1–yZryO2–x) nanocrystals for application as environmental catalysts. In contrast to typical anthropogenic synthesis routes, the crystalline oxide nanoparticles are formed at room temperature from an otherwise inert aqueous solution without the addition of a precipitant or additional reactant. An engineered form of silicatein, rCeSi, as a single enzyme not only catalyzes the direct biomineralization of the nanocrystalline oxides but also serves as a templating agent to control their morphological structure. The biomineralized nanocrystals of less than 3 nm in diameter are catalytically active toward carbon monoxide oxidation following an oxidative annealing step to remove carbonaceous residue. The introduction of zirconia into the nanocrystals leads to an increase in Ce(III) concentration, associated catalytic activity, and the thermal stability of the nanocrystals

An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).&lt;p&gt;&lt;/p&gt; Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.&lt;p&gt;&lt;/p&gt; Results: Every attribute in the DCE was statistically significant (p &#60; 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.&lt;p&gt;&lt;/p&gt; Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.&lt;p&gt;&lt;/p&gt

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment