Next generation risk assessment for occupational chemical safety - A real world example with sodium-2-hydroxyethane sulfonate.

Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g. under EU REACH. By contrast, a large proportion of regulatory worker safety assessments are underpinned by toxicological studies using experimental animals. Consequently, occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Here, a workflow for conducting NGRA under an occupational safety context was developed, which is illustrated with a case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were estimated using a standard occupational exposure model following a comprehensive life cycle assessment of SI and considering factory-specific data. Outputs of this model were then used to estimate internal exposures using a Physiologically Based Kinetic (PBK) model, which was constructed with SI specific Absorption, Distribution, Metabolism and Excretion (ADME) data. PBK modelling indicated a worst-case plasma maximum concentration (Cmax) of 0.8 µM across the SI life cycle. SI bioactivity was assessed in a battery of NAMs relevant to systemic, reproductive, and developmental toxicity; a cell stress panel, high throughput transcriptomics in three cell lines (HepG2, HepaRG and MCF-7 cells), pharmacological profiling and specific assays relating to developmental toxicity (Reprotracker and devTOX quickPredict). Points of Departure (PoDs) for SI ranged from 104 to 5044 µM. Cmax values obtained from PBK modelling of occupational exposures to SI were compared with PoDs from the bioactivity assays to derive Bioactivity Exposure Ratios (BERs) which demonstrated the safety for workers exposed to SI under current levels of factory specific risk management. In summary, the tiered and iterative workflow developed here represents an opportunity for integrating non animal approaches for a large subset of substances for which systemic worker safety assessment is required. Such an approach could be followed to ensure that animal testing is only conducted as a "last resort" e.g. under EU REACH.

High-grade B-cell lymphoma with a quadruple-hit genetic profile including concurrent MYC, BCL2, BCL6, and CCND1 gene rearrangements.

Several reports of concurrent MYC, BCL2, BCL6, and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a "quadruple-hit" genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC, BCL2, and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies. Of 203 cases meeting inclusion criteria, 2 (1%) with a quadruple-hit genetic profile were identified. Case 1 represented a 59-year-old female with widespread lymphadenopathy and a diagnosis of HGBL who exhibited primary refractoriness to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Case 2 represented a 58-year-old male with mediastinal and abdominal lymphadenopathy and a diagnosis of large BCL who died from disease after 1 cycle of DA-EPOCH-R chemotherapy. Similarly, a literature review of 7 previously reported cases of HGBL with a quadruple-hit profile also demonstrated aggressive disease behavior. Our study adds 2 new cases to the rarely encountered quadruple-hit HGBL, and a brief meta-analysis of the 9 available cases indicates aggressive disease behavior conferred by this constellation of genetic events.

Imaging of Castleman Disease.

Castleman disease (CD) is a group of rare and complex lymphoproliferative disorders that can manifest in two general forms: unicentric CD (UCD) and multicentric CD (MCD). These two forms differ in clinical manifestation, imaging appearances, treatment options, and prognosis. UCD typically manifests as a solitary enlarging mass that is discovered incidentally or after development of compression-type symptoms. MCD usually manifests acutely with systemic symptoms including fever and weight loss. As a whole, CD involves lymph nodes throughout the chest, neck, abdomen, pelvis, and axilla and can have a wide variety of imaging appearances. Most commonly, lymph nodes or masses in UCD occur in the chest, classically with well-defined borders, hyperenhancement, and possible characteristic patterns of calcification and/or feeding vessels. Lymph nodes affected by MCD, while also hyperenhancing, tend to involve multiple nodal chains and manifest alongside anasarca or hepatosplenomegaly. The polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) subtype of MCD may demonstrate lytic or sclerotic osseous lesions in addition to features typical of MCD. Since a diagnosis of CD based solely on imaging findings is often not possible, pathologic confirmation with core needle biopsy and/or surgical excision is necessary. Nevertheless, imaging plays a crucial role in supporting the diagnosis of CD, guiding appropriate regions for biopsy, and excluding other potential causes or mimics of disease. CT is frequently the initial imaging technique used in evaluating potential CD. MRI and PET play important roles in thoroughly evaluating the disease and determining its extent, especially the MCD form. Complete surgical excision is typically curative for UCD. MCD usually requires systemic therapy. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Co-occurrence of marine and freshwater phycotoxins in oysters, and analysis of possible predictors for management.

Oysters (Crassostrea virginica) were screened for 12 phycotoxins over two years in nearshore waters to collect baseline phycotoxin data and to determine prevalence of phycotoxin co-occurrence in the commercially and ecologically-relevant species. Trace to low concentrations of azaspiracid-1 and -2 (AZA1, AZA2), domoic acid (DA), okadaic acid (OA), and dinophysistoxin-1 (DTX1) were detected, orders of magnitude below seafood safety action levels. Microcystins (MCs), MC-RR and MC-YR, were also found in oysters (maximum: 7.12 µg MC-RR/kg shellfish meat wet weight), warranting consideration of developing action levels for freshwater phycotoxins in marine shellfish. Oysters contained phycotoxins that impair shellfish health: karlotoxin1-1 and 1-3 (KmTx1-1, KmTx1-3), goniodomin A (GDA), and pectenotoxin-2 (PTX2). Co-occurrence of phycotoxins in oysters was common (54%, n = 81). AZAs and DA co-occurred most frequently of the phycotoxins investigated that are a concern for human health (n = 13) and PTX2 and KmTxs co-occurred most frequently amongst the phycotoxins of concern for shellfish health (n = 9). Various harmful algal bloom (HAB) monitoring methods and tools were assessed for their effectiveness at indicating levels of phycotoxins in oysters. These included co-deployed solid phase adsorption toxin tracking (SPATT) devices, toxin levels in particulate organic matter (POM, >1.5 µm) and whole water samples and cell concentrations from water samples as determined by microscopy and quantitative real-time PCR (qPCR). The dominant phycotoxin varied between SPATTs and all other phycotoxin sample types, and out of the 11 phycotoxins detected in oysters, only four and seven were detected in POM and whole water respectively, indicating phycotoxin profile mismatch between ecosystem compartments. Nevertheless, there were correlations between DA in oysters and whole water (simple linear regression [LR]: R2 = 0.6, p < 0.0001, n = 40), and PTX2 in oysters and SPATTs (LR: R2 = 0.3, p = 0.001, n = 36), providing additional monitoring tools for these phycotoxins, but oyster samples remain the best overall indicators of seafood safety.

Recent results from non-basic glycosidase inhibitors: How structural diversity can inform general strategies for improving inhibition potency.

This review covers the literature in the past 15 years on glycosidase inhibitors lacking a basic nitrogen (for example iminosugars/azasugars) with a focus on natural terpenoids, and mono- and polycyclic aromatic hydrocarbons. From quite diverse structures, insight into inhibitor structural features that may be applicable to optimisation of all glycosidase inhibitors including iminosugars are identified.

Identification of EWSR1 rearrangements in patients with immature hematopoietic neoplasms: A case series and review of literature.

Rearrangement of the EWSR1 gene (22q12.2) is a well-recognized genetic lesion in bone and soft tissue tumors. However, few reports have suggested that EWSR1 rearrangements may also occur in the setting of hematopoietic tumors. We herein describe two cases of immature hematopoietic neoplasms presenting with EWSR1 rearrangements. The first occurred in a 41-year-old female diagnosed with mixed-phenotype acute leukemia, B/T/myeloid, in which conventional chromosome analysis revealed a t(2;22)(q35;q12). Further analysis with whole genome sequencing revealed that this rearrangement led to an EWSR1::FEV gene fusion. The second case was identified in an 18-year-old male with a high-grade B-cell lineage malignant neoplasm with immature features in which conventional chromosome analysis revealed a t(17;22)(q25;q12). Mate-pair sequencing, a next generation sequencing-based assay, was performed and revealed three in-frame chimeric gene fusions involving the EWSR1, TEF and STRADA gene regions. This report further expands the repertoire of hematopoietic neoplasms with EWSR1 fusions and partner genes involved in these rearrangements.

Drug-Drug Interactions in People Living With HIV at Risk of Hepatic and Renal Impairment: Current Status and Future Perspectives.

Despite the advancement of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV), drug-drug interactions (DDIs) remain a relevant clinical issue for people living with HIV receiving ART. Antiretroviral (ARV) drugs can be victims and perpetrators of DDIs, and a detailed investigation during drug discovery and development is required to determine whether dose adjustments are necessary or coadministrations are contraindicated. Maintaining therapeutic ARV plasma concentrations is essential for successful ART, and changes resulting from potential DDIs could lead to toxicity, treatment failure, or the emergence of ARV-resistant HIV. The challenges surrounding DDI management are complex in special populations of people living with HIV, and often lack evidence-based guidance as a result of their underrepresentation in clinical investigations. Specifically, the prevalence of hepatic and renal impairment in people living with HIV are between five and 10 times greater than in people who are HIV-negative, with each condition constituting approximately 15% of non-AIDS-related mortality. Therapeutic strategies tend to revolve around the treatment of risk factors that lead to hepatic and renal impairment, such as hepatitis C, hepatitis B, hypertension, hyperlipidemia, and diabetes. These strategies result in a diverse range of potential DDIs with ART. The purpose of this review was 2-fold. First, to summarize current pharmacokinetic DDIs and their mechanisms between ARVs and co-medications used for the prevention and treatment of hepatic and renal impairment in people living with HIV. Second, to identify existing knowledge gaps surrounding DDIs related to these special populations and suggest areas and techniques to focus upon in future research efforts.

Limited Expansion of Human Hepatocytes in FAH/RAG2-Deficient Swine.

The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. The expansion properties of human hepatocytes in immunodeficient mice are well known. However, little has been reported about larger animals that are more scalable and practical for clinical purposes. Therefore, we engineered immunodeficient swine to support expansion of human hepatocytes and identify barriers to their clinical application. Immunodeficient swine were engineered by knockout of the recombinase-activating gene 2 (RAG2) and fumarylacetoacetate hydrolase (FAH). Immature human hepatocytes (ihHCs) were injected into fetal swine by intrauterine cell transplantation (IUCT) at day 40 of gestation. Human albumin was measured as a marker of engraftment. Cytotoxicity against ihHCs was measured in transplanted piglets and control swine. We initially detected higher levels of human albumin in cord blood of newborn FAH/RAG2-deficient (FR) pigs compared with immunocompetent controls (196.26 ng/dL vs. 39.29 ng/dL, p = 0.008), indicating successful engraftment of ihHCs after IUCT and adaptive immunity in the fetus. Although rare hepatocytes staining positive for human albumin were observed, levels of human albumin did not rise after birth, but declined, suggesting rejection of xenografted ihHCs. Cytotoxicity against ihHCs increased after birth by 3.8% (95% CI: [2.1%-5.4%], p < 0.001) and inversely correlated with declining levels of human albumin (p = 2.1 × 10-5, R2 = 0.17). Circulating numbers of T cells and B cells were negligible in FR pigs. However, circulating natural killer (NK) cells exerted cytotoxicity against ihHCs. NK cell activity was lower in immunodeficient piglets after IUCT than in naive controls (30.4% vs. 40.1%, p = 0.011, 95% CI for difference [2.7%-16.7%]). In conclusion, ihHCs were successfully engrafted in FR swine after IUCT. NK cells were a significant barrier to expansion of hepatocytes. New approaches are needed to overcome this hurdle and allow large-scale expansion of human hepatocytes in immunodeficient swine. Impact statement There is currently a need for robust expansion of human hepatocytes. We describe an immunodeficient swine model into which we engrafted immature human hepatocytes (ihHCs). We identified the mechanism of the eventual graft rejection by the intact NK cell population, which has not been previously shown to have a significant role in xenograft rejection. By both improving engraftment and reducing NK cell-mediated cytotoxicity toward the graft through intrauterine cell transfer, we confirmed the presence of residual adaptive immunity in this model of immunodeficiency and the ability to induce hyposensitization in the NK cell population by taking advantage of the fetal microenvironment.

Spatiotemporal distribution of phycotoxins and their co-occurrence within nearshore waters.

Harmful algal blooms (HABs), varying in intensity and causative species, have historically occurred throughout the Chesapeake Bay, U.S.; however, phycotoxin data are sparse. The spatiotemporal distribution of phycotoxins was investigated using solid-phase adsorption toxin tracking (SPATT) across 12 shallow, nearshore sites within the lower Chesapeake Bay and Virginia's coastal bays over one year (2017-2018). Eight toxins, azaspiracid-1 (AZA1), azaspiracid-2 (AZA2), microcystin-LR (MC-LR), domoic acid (DA), okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-2 (PTX2), and goniodomin A (GDA) were detected in SPATT extracts. Temporally, phycotoxins were always present in the region, with at least one phycotoxin group (i.e., consisting of OA and DTX1) detected at every time point. Co-occurrence of phycotoxins was also common; two or more toxin groups were observed in 76% of the samples analyzed. Toxin maximums: 0.03 ng AZA2/g resin/day, 0.25 ng DA/g resin/day, 15 ng DTX1/g resin/day, 61 ng OA/g resin/day, 72 ng PTX2/g resin/day, and 102,050 ng GDA/g resin/day were seasonal, with peaks occurring in summer and fall. Spatially, the southern tributary and coastal bay regions harbored the highest amount of total phycotoxins on SPATT over the year, and the former contained the greatest diversity of phycotoxins. The novel detection of AZAs in the region, before a causative species has been identified, supports the use of SPATT as an explorative tool in respect to emerging threats. The lack of karlotoxin in SPATT extracts, but detection of Karlodinium veneficum by microscopy, however, emphasizes that this tool should be considered complementary to, but not a replacement for, more traditional HAB management and monitoring methods.

Toward sustainable desalination using food waste: capacitive desalination with bread-derived electrodes.

Each year approximately 1.3 billion tons of food is either wasted or lost. One of the most wasted foods in the world is bread. The ability to reuse wasted food in another area of need, such as water scarcity, would provide a tremendous sustainable outcome. To address water scarcity, many areas of the world are now implementing desalination. One desalination technology that could benefit from food waste reuse is capacitive deionization (CDI). CDI has emerged as a powerful desalination technology that essentially only requires a pair of electrodes and a low-voltage power supply. Developing freestanding carbon electrodes from food waste could lower the overall cost of CDI systems and the environmental and economic impact from food waste. We created freestanding CDI electrodes from bread. The electrodes possessed a hierarchical pore structure that enabled both high salt adsorption capacity and one of the highest reported values for hydraulic permeability to date in a flow-through CDI system. We also developed a sustainable technique for electrode fabrication that does not require the use of common laboratory equipment and could be deployed in decentralized locations and developing countries with low-financial resources.

Crystal structure of 6-azido-6-de-oxy-1,2-O-iso-propyl-idene-α-d-gluco-furan-ose.

Short syntheses to high Fsp 3 index natural-product analogues such as imino-sugars are of paramount importance in the investigation of their biological activities and reducing the use of protecting groups is an advantageous synthetic strategy. An iso-propyl-idene group was employed towards the synthesis of seven-membered ring imino-sugars and the title compound, C9H15N3O5, was crystallized as an inter-mediate, in which the THF ring is twisted and the dioxolane ring adopts an envelope conformation: the dihedral angle between the rings is 67.50 (13)°. In the crystal, the hydroxyl groups participate in O-H⋯(O,O) and O-H⋯N hydrogen-bonding inter-actions, which generate chains of mol-ecules propagating parallel to the a-axis direction. There is a notable non-classical C-H⋯O hydrogen bond, which cross-links the [100] chains into (001) sheets.

Analysis and impact of a multidisciplinary lymphoma virtual tumor board.

The aim is to prospectively evaluate the impact of a multidisciplinary lymphoma virtual tumor board. The utility of multi-site interactive lymphoma-specific tumor boards has not been reported. The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN). The format includes the clinical case presentation, presentation of radiology and hematopathology findings by the appropriate subspecialist, proposed treatment options, review of the literature pertinent to the case, pharmacy contributions, and discussion followed by recommendations. Three hundred and nine consecutive highly selected real-time cases with a diagnosis of lymphoma were presented at the Mayo Clinic Lymphoma Tumor Board from January 2014 to June 2018 and decisions were prospectively tracked to assess its impact on the treatment decisions. A total of 309 cases were prospectively evaluated. One hundred and forty (45.3%) cases had some changes made or recommended. The total changes suggested were 179, as some cases had more than one recommendation. There were 93 (30%) clinical management recommendations, 45 (14.6%) additional testing recommendations, 29 (9.4%) pathology changes, and 6 (1.9%) radiology changes. In an electronic evaluation process, 93% of the responders reported an improvement in knowledge and competence, and 100% recommended no change in format of the board. A multidisciplinary lymphoma tumor board approach was found to have a meaningful impact on lymphoma patients while enhancing interdisciplinary interactions and education for multiple levels of the clinical care team.

Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers.

Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.

Secondary acquisition of BCR-ABL1 fusion in de novo GATA2-MECOM positive acute myeloid leukemia with subsequent emergence of a rare KMT2A-ASXL2 fusion.

Secondary acquisition of t(9;22)(q34;q11.2)/BCR-ABL1 fusion in the context of de novo acute myeloid leukemia (AML) with inv(3)(q21q26)/GATA2-MECOM rearrangement has been rarely reported. Furthermore, t(2;11)(p23;q23)/KMT2A-ASXL2 fusion has been rarely described with only a single case reported to date. We report a 45-year-old male with a diagnosis of de novo AML harboring GATA2-MECOM rearrangement in conjunction with a related subclone with concomitant inv(3) and t(9;22). The patient was treated with a tyrosine kinase inhibitor (TKI) which lead to disappearance of the inv(3)/t(9;22) subclone and subsequent expansion of the inv(3) ancestral clone. The patient was started on a 7+3 induction regimen with TKI but had persistent disease. He was placed on several additional treatment protocols and only achieved morphologic remission with a combination of fludarabine, cytarabine and filgrastim with TKI. Approximately 11.5 months after diagnosis the patient relapsed with the inv(3) clone predominating initially, followed by return of the inv(3)/t(9;22) subclone and the emergence of a second subclone with concomitant inv(3) and t(2;11)(p23;q23). Mate-pair sequencing was performed and identified a KMT2A-ASXL2 in-frame fusion, which was only recently described in a single case of therapy-related AML. For BCR-ABL1 positive AML, which generally carries a poor prognosis, treatment with TKIs has been proposed in combination with standard chemotherapy. In our case, treatment with TKI alone led to initial response of the BCR-ABL1 positive clone, but the ancestral clone quickly expanded and subsequent standard AML therapy may have led to further clonal evolution and re-emergence of the BCR-ABL1 clone in the absence of therapeutic selection.

Ventricle-predominant primary CNS lymphomas: clinical, radiological and pathological evaluation of five cases and review of the literature.

Primary central nervous system lymphomas (PCNSLs) are typically intraparenchymal. A subset of PCNSLs predominantly arises in the ventricles, with minimal parenchymal involvement. We review the clinical, radiological, and pathological features of ventricle-predominant PCNSLs (VP-PCNSLs) in 40 previously reported cases and report 5 additional cases. Including all cases of VP-PCNSLs (n = 45), 38% were diffuse large B-cell lymphomas (DLBCL), 11% were Burkitt lymphomas, 7% were MALT lymphomas, 4% were T-cell lymphomas, and 40% were lymphomas, not otherwise classified. VP-PCNSLs show rapid clinical progression. Patients present at a median age of 60.5 years. Unique clinical and radiological features distinguish them from other intraventricular tumors, including advanced age, edema, multifocality, hyperdensity, early and avid post-contrast enhancement, restricted diffusion, and positron emission tomography (PET) hypermetabolism. Including our cases, which were all DLBCL, and all previously reported DLBCL cases (n = 10), 8 of 10 show germinal center B-cell-like (GCB) phenotype, contrasting the high prevalence of non-germinal center B-cell-like (non-GCB) phenotype of parenchymal DLBCL PCNSLs. MYD88 L265P mutation was detected in three of our five cases. Ventricle-predominant PCNSLs are clinically and radiologically distinct, and the DLBCLs may be pathologically distinct. Further recognition of this entity may help to evaluate the role of therapies, possibly including surgical resection.

Intact mangrove root electrodes for desalination.

Through the benefit of billions of years of evolution, biology has developed tremendous strategies on how to co-exist in high salinity and water scarce environments. Biologically-inspired abiotic systems are becoming a central pillar in how we respond to critical grand challenges that accompany exponential population growth, uncontrolled climate change and the harsh reality that 96.5% of the water on the planet is saltwater. One fascinating biologic adaptation to saltwater is the growth of mangrove trees in brackish swamps and along the coasts. Through a process of salt exclusion, the mangrove maintains a near freshwater flow from roots to leaves to survive. One abiotic approach to water desalination is capacitive deionization, which aims to desalinate low-salinity water sources at energy costs below current technologies, such as reverse osmosis and thermal distillation. In this work, we use one-step carbonization of a plant with developed aerenchyma tissue to enable highly-permeable, freestanding flow-through capacitive deionization electrodes. We show that carbonized aerenchyma from red mangrove roots reduces the resistance to water flow through electrodes by 65-fold relative to carbonized common woody biomass. We then demonstrate the practical use of the intact carbonized red mangrove roots as electrodes in a flow-through capacitive deionization system. These findings have implications in a range of fields including water desalination, bioinspired materials, and plant functionality.

A biosensing soft robot: Autonomous parsing of chemical signals through integrated organic and inorganic interfaces.

The integration of synthetic biology and soft robotics can fundamentally advance sensory, diagnostic, and therapeutic functionality of bioinspired machines. However, such integration is currently impeded by the lack of soft-matter architectures that interface synthetic cells with electronics and actuators for controlled stimulation and response during robotic operation. Here, we synthesized a soft gripper that uses engineered bacteria for detecting chemicals in the environment, a flexible light-emitting diode (LED) circuit for converting biological to electronic signals, and soft pneu-net actuators for converting the electronic signals to movement of the gripper. We show that the hybrid bio-LED-actuator module enabled the gripper to detect chemical signals by applying pressure and releasing the contents of a chemical-infused hydrogel. The biohybrid gripper used chemical sensing and feedback to make actionable decisions during a pick-and-place operation. This work opens previously unidentified avenues in soft materials, synthetic biology, and integrated interfacial robotic systems.

Annealing-induced precipitate formation behavior in MOVPE-grown GaAs1-x Bi x explored by atom probe tomography and HAADF-STEM.

The effects of a 45 min anneal at 800 °C on the physical properties and microstructure of a five-period GaAs1-x Bi x /GaAs1-y Bi y superlattice with y ≠ x were studied using room-temperature photoluminesence spectroscopy, high-resolution x-ray diffraction, high-angle annular-dark-field scanning transmission electron microscopy (HAADF-STEM), and atom probe tomography (APT). The anneal resulted in a substantial increase of the photoluminesence intensity over that observed in the as-deposited sample, indicating annihilation of non-radiative recombination centers and stability of the superlattice structure during the anneal. However, some precipitation of Bi from the GaAs1-x Bi x also occurred. The characteristics of phase separation that occurred within these precipitates were investigated in detail by APT and HAADF-STEM. They indicate that the precipitation reaction involves formation of embedded nano-scale liquid droplets that can accelerate local Bi dissolution from the GaAs1-x Bi x matrix by moving through it. Preservation of nanometer scale sharp Bi concentration gradients in the growth direction suggested that very little solid state diffusion of Bi occurred during the anneal. The observed gradient in precipitate number density with distance from the sample surface further supports hypotheses of an enabling role of Ga vacancies in the precipitation process.

Anoxybacillus sp. Strain UARK-01, a New Thermophilic Soil Bacterium with Hyperthermostable Alkaline Laccase Activity.

We describe the isolation and characteristics of a novel thermophilic bacterium from soil. The organism is a member of the Anoxybacillus genus based on phylogenetic analysis of the 16S rRNA gene. The 16S rRNA of the organism shares >99% sequence identity with those of two species, Anoxybacillus rupiensis and A. geothermalis. We named this isolate as Anoxybacillus sp. strain UARK-01. UARK-01 grows optimally in the presence of oxygen at 55 °C and pH 8. It grew excellently in the presence of lignin as the sole carbon source. Culture supernatant from UARK-01 grown on lignin was rich in laccase activity. The laccase activity was optimal at 90 °C and pH 9, and there was comparable activity at 80 and 100 °C. The crude laccase decolorized approximately 75% of Congo Red in 7 h under optimal conditions. A single laccase gene was identified from the draft genome sequence of Anoxybacillus sp. UARK-01. The UARK-01 laccase (Anox_Lacc) was cloned and overexpressed in Escherichia coli and was partially purified. The partially purified Anox_Lacc decolorized approximately 1.64+/0.21 nanomoles of Congo Red per microgram protein in 30 min at 90 °C and pH 9. Anox_Lacc is a member of the multicopper polyphenol oxidoreductase laccase family (pfam02578 Cu-oxidase_4) and has novel characteristics. Multiple sequence analysis of Anox_Lacc with six homologs from the family revealed four conserved copper ligands and several new residues that are fully conserved. Anox_Lacc is enriched in leucine, glutamine, and lysine, and it contains fewer alanine, arginine, glycine, and serine residues. Skewed amino acid composition of Anox_Lacc likely contributes to the exceptional thermochemical properties of the laccase activity from UARK-01. Both lignin utilization and production of hyperthermostable alkaline laccase are new findings in the Anoxybacillus genus.