Are There Too Many Lawyers--Introductory Remarks

The largest wastewater treatment plant in Jordan was monitored in the summer to determine the removal of pharmaceuticals and personal care products (PPCPs). Grab samples were collected from the influent and effluent of As-Samra Wastewater Treatment Plant (WWTP). Liquid chromatography and tandem mass spectrometry (LC–MS/MS) were utilized to determine the concentrations of 18 compounds of pharmaceuticals and personal care products (PPCPs). The results showed that 14 compounds were detected in the collected samples from the influent and effluent of As-Samra WWTP. These compounds are 1,7-dimethylxanthine, amphetamine, acetaminophen, caffeine, carbamazepine, cimetidine, cotinine, diphenhydramine, methylenedioxymethamphetamine (MDMA), morphine, phenazone, sulfamethazine, sulfamethoxazole, thiabendazole, and trimethoprim. However, four compounds were below the detection limit

Removal of Carbamazepine onto Modified Zeolitic Tuff in Different Water Matrices: Batch and Continuous Flow Experiments

Carbamazepine (CBZ) is the most frequently detected pharmaceutical residues in aquatic environments effluent by wastewater treatment plants. Batch and column experiments were conducted to evaluate the removal of CBZ from ultra-pure water and wastewater treatment plant (WWTP) effluent using raw zeolitic tuff (RZT) and surfactant modified zeolite (SMZ). Point zero net charge (pHpzc), X-ray diffraction (XRD), X-ray fluorescence (XRF), and Fourier Transform Infrared (FTIR) were investigated for adsorbents to evaluate the physiochemical changes resulted from the modification process using Hexadecyltrimethylammonium bromide (HDTMA-Br). XRD and FTIR showed that the surfactant modification of RZT has created an amorphous surface with new alkyl groups on the surface. The pHpzc was determined to be approximately 7.9 for RZT and SMZ. The results indicated that the CBZ uptake by SMZ is higher than RZT in all sorption tests (\u3e8 fold). Batch results showed that the sorption capacity of RZT and SMZ in WWTP effluent (0.029 and 0.25 mg/g) is higher than RZT and SMZ (0.018 and 0.14 mg/g) in ultrapure water (1.6–1.8 fold). Batch tests showed that the equilibrium time of CBZ removal in the WWTP matrix (47 h) is much longer than CBZ removal in ultrapure water. The sorption capacity of RZT & SMZ in WWTP effluent (0.03, 0.33 mg/g) is higher than RZT and SMZ (0.02 and 0.17 mg/g) in ultrapure water (1.5–2 fold) using column test. This study has clearly demonstrated that the performance of RZT and SMZ is more efficient for the removal of CBZ from realistic wastewater than ultrapure water. It is evident that the surfactant modification of RZT has enhanced the CBZ removal in both matrices

Removal of carbamazepine onto modified zeolitic tuff in different water matrices: Batch and continuous flow experiments

Carbamazepine (CBZ) is the most frequently detected pharmaceutical residues in aquatic environments effluent by wastewater treatment plants. Batch and column experiments were con-ducted to evaluate the removal of CBZ from ultra-pure water and wastewater treatment plant (WWTP) effluent using raw zeolitic tuff (RZT) and surfactant modified zeolite (SMZ). Point zero net charge (pHpzc), X-ray diffraction (XRD), X-ray fluorescence (XRF), and Fourier Transform Infrared (FTIR) were investigated for adsorbents to evaluate the physiochemical changes resulted from the modification process using Hexadecyltrimethylammonium bromide (HDTMA-Br). XRD and FTIR showed that the surfactant modification of RZT has created an amorphous surface with new alkyl groups on the surface. The pHpzc was determined to be approximately 7.9 for RZT and SMZ. The results indicated that the CBZ uptake by SMZ is higher than RZT in all sorption tests (\u3e8 fold). Batch results showed that the sorption capacity of RZT and SMZ in WWTP effluent (0.029 and 0.25 mg/g) is higher than RZT and SMZ (0.018 and 0.14 mg/g) in ultrapure water (1.6–1.8 fold). Batch tests showed that the equilibrium time of CBZ removal in the WWTP matrix (47 h) is much longer than CBZ removal in ultrapure water. The sorption capacity of RZT & SMZ in WWTP effluent (0.03, 0.33 mg/g) is higher than RZT and SMZ (0.02 and 0.17 mg/g) in ultrapure water (1.5–2 fold) using column test. This study has clearly demonstrated that the performance of RZT and SMZ is more efficient for the removal of CBZ from realistic wastewater than ultrapure water. It is evident that the surfactant modification of RZT has enhanced the CBZ removal in both matrices

Engineering substrate promiscuity in halophilic alcohol dehydrogenase (HvADH2) by in silico design

An alcohol dehydrogenase from the halophilic archaeon Haloferax volcanii (HvADH2) has been engineered by rational design to broaden its substrate scope towards the conversion of a range of aromatic substrates, including flurbiprofenol, that is an intermediate of the non-steroidal anti-inflammatory drug, flurbiprofen. Wild-type HvADH2 showed minimal activity with flurbiprofenol (11.1 mU/mg). A homology model of HvADH2 was built and docking experiments with this substrate revealed that the biphenyl rings of flurbiprofenol formed strong interactions with residues F85 and F108, preventing its optimal binding in the active site. Mutations at position 85 however did not increase activity. Site directed mutagenesis at position F108 allowed the identification of three variants showing a significant (up to 2.3-fold) enhancement of activity towards flurbiprofenol, when compared to wild-type HvADH2. Interestingly, F108G variant did not show the classic inhibition in the presence of (R)-enantiomer when tested with rac-1-phenylethanol, underling its potential in racemic resolution of secondary alcohols

Haloquadratum walsbyi yields a versatile, NAD+/NADP+ dual affinity, thermostable, alcohol dehydrogenase (HwADH)

This study presents the first example of an alcohol dehydrogenase (ADH) from the halophilic archaeum Haloquadratum walsbyi (HwADH). A hexahistidine-tagged recombinant HwADH was heterologously overexpressed in Haloferax volcanii. HwADH was purified in one step and was found to be thermophilic with optimal activity at 65 °C. HwADH was active in the presence of 10 % (v/v) organic solvent. The enzyme displayed dual cofactor specificity and a broad substrate scope, maximum activity was detected with benzyl alcohol and 2-phenyl-1- propanol. HwADH accepted aromatic ketones, acetophenone and phenylacetone as substrates. The enzyme also accepted cyclohexanol and aromatic secondary alcohols, 1- phenylethanol and 4-phenyl-2-butanol. H. walsbyi may offer an excellent alternative to other archaeal sources to expand the toolbox of halophilic biocatalysts

Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation.

Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are not well understood. Here we have provided evidence that aberrant splicing by mutant SF3B1 altered the transcriptome, proteome, and metabolome of human cells, leading to missplicing-associated downregulation of metabolic genes, decreased mitochondrial respiration, and suppression of the serine synthesis pathway. We also found that mutant SF3B1 induces vulnerability to deprivation of the nonessential amino acid serine, which was mediated by missplicing-associated downregulation of the serine synthesis pathway enzyme PHGDH. This vulnerability was manifest both in vitro and in vivo, as dietary restriction of serine and glycine in mice was able to inhibit the growth of SF3B1MUT xenografts. These findings describe a role for SF3B1 mutations in altered energy metabolism, and they offer a new therapeutic strategy against SF3B1MUT cancers

Highlights of the ERS Lung Science Conference and Sleep and Breathing Conference 2021 and the new ECMC members

The Lung Science Conference (LSC) and the Sleep and Breathing Conference (SBC) are two conferences organised by the European Respiratory Society (ERS), the latter held in association with the European Sleep Research Society. This year, the LSC and SBC were both held in a virtual format with the participation of researchers and clinicians from around the world. The participation of Early Career Members (ECMs) was notable in both events: 216 of 363 (60%) delegates attending the LSC were under 40?years old, and 315 of 920 (34%) delegates were ?40?years of age at the SBC. Both conferences included outstanding talks on the most recent advances in respiratory medicine and science, oral/poster communication sessions on novel research, exciting opportunities to network with peers, and much more!This paper provides a brief overview of some of the most remarkable sessions of the LSC and SBC, written by ECMs attending the sessions.We also present the new members of the Early Career Member Committee (ECMC) of the ERS from Assemblies 1, 4, 10, 12 and 13, who were elected in the latest round of ERS elections. Welcome aboard

The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets

Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts.

Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. Sf3b1K700E/+ animals had impaired erythropoiesis and progressive anemia without ringed sideroblasts, as well as reduced hematopoietic stem cell numbers and host-repopulating fitness. To understand the molecular basis of these observations, we analyzed global RNA splicing in Sf3b1K700E/+ hematopoietic cells. Aberrant splicing was associated with the usage of cryptic 3' splice and branchpoint sites, as described for human SF3B1 mutants. However, we found a little overlap between aberrantly spliced mRNAs in mouse versus human, suggesting that anemia may be a consequence of globally disrupted splicing. Furthermore, the murine orthologues of genes associated with ring sideroblasts in human MDS, including Abcb7 and Tmem14c, were not aberrantly spliced in Sf3b1K700E/+ mice. Our findings demonstrate that, despite significant differences in affected transcripts, there is overlap in the phenotypes associated with SF3B1-K700E between human and mouse. Future studies should focus on understanding the basis of these similarities and differences as a means of deciphering the consequences of spliceosome gene mutations in MDS