Highly reusable Bi2O3/electron-Cu-shuttle in-situ immobilized polyacrylonitrile fibrous mat for efficient photocatalytic degradation of methylene blue and rhodamine B dyes.

Organic semiconductor-based photocatalysts have been alluring due to their edge over inorganic photocatalysts. In this study, a reusable copper-bismuth oxide/polyacrylonitrile (Cu-Bi2O3/PAN) fibrous mat was prepared by fast-process flame spray pyrolysis and electrospinning for photocatalytic degradation of methylene blue (MB) and rhodamine B (RhB) dyes. The results confirmed a well-defined morphology of Cu-Bi2O3/PAN fibers and good coordination of flame-made Cu-Bi2O3 particles with the functional groups of PAN. The Cu-Bi2O3/PAN fibrous mat exhibits remarkable photocatalytic performance of 96.2% MB and 98.6% RhB degradation, with a reaction rate as high as about 4.5- and 10.2-times than that of flame-made Cu-Bi2O3 particles and PAN under neutral condition, even after 10 cycles. The Cu-Bi2O3/PAN exhibits complete degradation of MB and RhB in 90 and 150 min under alkaline and slightly acidic conditions, respectively. The synergistic effect of Cu-Bi2O3 and coordination bond between particles and functional groups of PAN promoted carrier migration, suppressed recombination of carriers and provided abundant radicals on the surface of the mat. Superoxide and hydroxyl radicals were the major active species involved in the degradation of RhB and MB, respectively. This work provides an insight into designing the Cu-metal-shuttle based photocatalysts to optimize fibrous mat application in water remediation.

Retention of methyl iodide on metal and TEDA impregnated activated carbon using indigenously developed setup.

Removal of methyl iodide (CH3I) from the air present within nuclear facilities is a critical issue. In case of any nuclear accident, there is a great need to mitigate the radioactive organic iodide immediately as it accumulates in human bodies, causing severe consequences. Current research focuses on removing organic iodides, for which the surface of activated carbon (AC) was modified by impregnating it with different metals individually, i.e. Ag, Ni, Zn, Cu and with the novel combination of these four metals (AZNC). After the impregnation of metals, triethylenediamine (TEDA) was coated on metal impregnated activated carbon (IAC) surface. The adsorption capacity of the combination of four metals IAC was found to be 276 mg/g as the maximum for the trapping of CH3I. Whereas TEDA-metal impregnation on ACs enhanced the removal efficiency of CH3I up to 352 mg/g. After impregnation, adsorption capacity of AZNC and AZNCT is significantly higher as compared to AC. According to the finding, t5% of AZNCT IAC is 46 min, which is considerably higher than the t5% of other tested adsorbents. According to isotherm fitting data, Langmuir isotherm was found superior for describing CH3I sorption onto AC and IACs. Kinetics study shows that pseudo second order model represented the sorption of CH3I more accurately than the pseudo first order. Thermodynamic studies gave negative value of ΔG which shows that the reaction is spontaneous in nature. Based on the findings, AZNCT IAC appears to have a great potential for air purification applications in order to obtain clean environment.

BiP inactivation due to loss of the deAMPylation function of FICD causes a motor neuron disease.

PURPOSE: The chaperone protein BiP is the master regulator of the unfolded protein response in the endoplasmic reticulum. BiP chaperone activity is regulated by the post-translational modification AMPylation, exclusively provided by FICD. We investigated whether FICD variants identified in patients with motor neuron disease could interfere with BiP activity regulation. METHODS: Exome sequencing was performed to identify causative pathogenic variants associated with motor neuron diseases. Functional studies were conducted on fibroblasts from patients to explore the molecular mechanism of the disease. RESULTS: We identified biallelic variants in FICD causing a neurodegenerative disease of upper and lower motor neurons. Affected individuals harbor a specific missense variant, Arg374His, positioned in the catalytic motif of the enzyme and important for adenosine triphosphate binding. The mutated residue abolishes intramolecular interaction with the regulatory residue Glu234, essential to inhibit AMPylation and to promote de-AMPylation by FICD. Consequently, fibroblasts from patients with FICD variants have abnormally increased levels of AMPylated and thus inactivated BiP. CONCLUSION: Loss of BiP chaperone activity in patients likely results in a chronic impairment of the protein quality control system in the endoplasmic reticulum. These findings will guide the development of therapeutic strategies for motoneuron and related diseases linked to proteotoxic stress.

Dysfunction of GRAP, encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss.

We have identified a GRAP variant (c.311A>T; p.Gln104Leu) cosegregating with autosomal recessive nonsyndromic deafness in two unrelated families. GRAP encodes a member of the highly conserved growth factor receptor-bound protein 2 (GRB2)/Sem-5/drk family of proteins, which are involved in Ras signaling; however, the function of the growth factor receptor-bound protein 2 (GRB2)-related adaptor protein (GRAP) in the auditory system is not known. Here, we show that, in mouse, Grap is expressed in the inner ear and the protein localizes to the neuronal fibers innervating cochlear and utricular auditory hair cells. Downstream of receptor kinase (drk), the Drosophila homolog of human GRAP, is expressed in Johnston's organ (JO), the fly hearing organ, and the loss of drk in JO causes scolopidium abnormalities. drk mutant flies present deficits in negative geotaxis behavior, which can be suppressed by human wild-type but not mutant GRAP. Furthermore, drk specifically colocalizes with synapsin at synapses, suggesting a potential role of such adaptor proteins in regulating actin cytoskeleton dynamics in the nervous system. Our findings establish a causative link between GRAP mutation and nonsyndromic deafness and suggest a function of GRAP/drk in hearing.

Assessment of arsenic exposure by drinking well water and associated carcinogenic risk in peri-urban areas of Vehari, Pakistan.

Arsenic (As) is a highly toxic and carcinogenic element. It has received considerable consideration worldwide in recent years due to its highest toxicity to human, and currently, high concentrations observed in the groundwater. Some recent media and research reports also highlighted possible As contamination of groundwater systems in Pakistan. However, there is a scarcity of data about As contents in groundwater in different areas/regions of the country. Consequently, the current study estimated the As concentration in the groundwater used for drinking purpose in 15 peri-urban sites of district Vehari, Pakistan. In total, 127 groundwater samples were collected and examined for As contents in addition to physicochemical characteristics such as temperature, electrical conductivity, pH, total soluble salts, chloride, carbonates, bicarbonates, sodium, potassium, lithium, calcium and barium. Results indicated that the groundwater samples were not fully fit for drinking purposes with several parameters, especially the alarming levels of As (mean As: 46.9 µg/L). It was found that 83% groundwater samples of peri-urban sites in district Vehari have As concentration greater than WHO lower permissible limit (10 µg/L). The risk assessment parameters (mean hazard quotient: 3.9 and mean cancer risk: 0.0018) also showed possible carcinogenic and non-carcinogenic risks associated with ingestion of As-contaminated groundwater at peri-urban sites. Based on the findings, it is anticipated that special monitoring and management of groundwater is necessary in the studied area in order to curtail the health risks associated with the use of As-contaminated drinking water. Moreover, appropriate remediation and removal of As from groundwater is also imperative for the study area before being used for drinking purpose to avoid As exposure and related risks to the local community.

Cadmium Partitioning, Physiological and Oxidative Stress Responses in Marigold (Calendula calypso) Grown on Contaminated Soil: Implications for Phytoremediation.

Marigold (Calendula calypso) is a multipurpose ornamental plant, but its cadmium (Cd) tolerance and phytoremediation potential is unknown. The proposed study was carried out to unravel Cd partitioning, physiological and oxidative stress responses of C. calypso grown under Cd stress. Plants were grown for four months in pots having different soil Cd levels: 0, 25, 50, 75, and 100 mg kg-1 soil. Plant growth, biomass, photosynthetic pigments, leaf water contents, stomatal conductance, and membrane stability index were not decreased at 25 mg kg-1 Cd. At higher levels of Cd stress, activities of antioxidant enzymes (SOD, APX, CAT, POD) increased to mitigate H2O2 and lipid peroxidation. Cadmium uptake in plants increased with increasing soil Cd levels, and roots accumulated a greater portion of Cd, followed by shoots and flowers, respectively. On the basis of Cd accumulation and its tolerance, it was determined that C. calypso can be successfully grown for phytostabilization of Cd contaminated soils.

Novel variant p.E269K confirms causative role of PLS1 mutations in autosomal dominant hearing loss.

Auditory reception relies on the perception of mechanical stimuli by stereocilia and its conversion to electrochemical signal. Mechanosensory stereocilia are abundant in actin, which provides them with structural conformity necessary for perception of auditory stimuli. Out of three major classes of actin-bundling proteins, plastin 1 encoded by PLS1, is highly expressed in stereocilia and is necessary for their regular maintenance. A missense PLS1 variant associated with autosomal dominant hearing loss (HL) in a small family has recently been reported. Here, we present another PLS1 missense variant, c.805G > A (p.E269K), in a Turkish family with autosomal dominant non-syndromic HL confirming the causative role of PLS1 mutations in HL. We propose that HL due to the p.E269K variant is from the loss of a stable PLS1-ACTB interaction.

SCO2 mutations cause early-onset axonal Charcot-Marie-Tooth disease associated with cellular copper deficiency.

Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome c oxidase (COX) assembly protein, have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency. Significantly expanding the known phenotypic spectrum, we identified compound heterozygous variants in SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot-Marie-Tooth disease type 4. Different from previously described cases, our patients developed predominantly motor neuropathy, they survived infancy, and they have not yet developed the cardiomyopathy that causes death in early infancy in reported patients. Both of our patients harbour missense mutations near the conserved copper-binding motif (CXXXC), including the common pathogenic variant E140K and a novel change D135G. In addition, each patient carries a second mutation located at the same loop region, resulting in compound heterozygote changes E140K/P169T and D135G/R171Q. Patient fibroblasts showed reduced levels of SCO2, decreased copper levels and COX deficiency. Given that another Charcot-Marie-Tooth disease gene, ATP7A, is a known copper transporter, our findings further underline the relevance of copper metabolism in Charcot-Marie-Tooth disease.

ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice.

Hair cells of the inner ear, the mechanosensory receptors, convert sound waves into neural signals that are passed to the brain via the auditory nerve. Little is known about the molecular mechanisms that govern the development of hair cell-neuronal connections. We ascertained a family with autosomal recessive deafness associated with a common cavity inner ear malformation and auditory neuropathy. Via whole-exome sequencing, we identified a variant (c.2207G>C, p.R736T) in ROR1 (receptor tyrosine kinase-like orphan receptor 1), cosegregating with deafness in the family and absent in ethnicity-matched controls. ROR1 is a tyrosine kinase-like receptor localized at the plasma membrane. At the cellular level, the mutation prevents the protein from reaching the cellular membrane. In the presence of WNT5A, a known ROR1 ligand, the mutated ROR1 fails to activate NF-κB. Ror1 is expressed in the inner ear during development at embryonic and postnatal stages. We demonstrate that Ror1 mutant mice are severely deaf, with preserved otoacoustic emissions. Anatomically, mutant mice display malformed cochleae. Axons of spiral ganglion neurons show fasciculation defects. Type I neurons show impaired synapses with inner hair cells, and type II neurons display aberrant projections through the cochlear sensory epithelium. We conclude that Ror1 is crucial for spiral ganglion neurons to innervate auditory hair cells. Impairment of ROR1 function largely affects development of the inner ear and hearing in humans and mice.

Effect of salinity on cadmium tolerance, ionic homeostasis and oxidative stress responses in conocarpus exposed to cadmium stress: Implications for phytoremediation.

Contamination of soil with salinity and Cd negatively affects growth and productivity of plants. The proposed study has been planned to explore the effects of salinity on Cd uptake, tolerance and phytoremediation potential of conocarpus (Conocarpus erectus L.). One-month-old uniform plants of conocarpus were exposed to 0, 8.9, 44.5, 89 and 178 µM Cd alone or in combination with 0, 100 and 200 mM NaCl in Hoagland's nutrient solution. Results revealed that shoot and root biomasses, leaf water content and pigment content decreased more in response to combination of Cd and salinity compared to Cd alone. The Na+ and Cl- concentrations in shoot and root were not affected by Cd alone, but increased in Cd + salinity treatments. The K+ concentration decreased by Cd alone as well as Cd combination with salinity. Plant Cd uptake increased in the presence of salinity but its translocation from root to shoot remained unaffected. Exposure of plants to Cd alone and Cd + salinity caused oxidative stress via overproduction of H2O2 and inducing lipid peroxidation. The activities of antioxidant enzymes such as SOD, CAT, POD and APX increased to mitigate this oxidative stress. It is concluded that the tolerance of conocarpus against Cd stress is decreased in the presence of salinity due to increased uptake of toxic ions and intensification of oxidative stress. Moreover, the Cd uptake behavior of this tree indicates its suitability for phytostabilization of Cd contaminated saline and non-saline soils.