DataSheet_1_Complete variable domain sequences of monoclonal antibody light chains identified from untargeted RNA sequencing data.fasta

IntroductionMonoclonal antibody light chain proteins secreted by clonal plasma cells cause tissue damage due to amyloid deposition and other mechanisms. The unique protein sequence associated with each case contributes to the diversity of clinical features observed in patients. Extensive work has characterized many light chains associated with multiple myeloma, light chain amyloidosis and other disorders, which we have collected in the publicly accessible database, AL-Base. However, light chain sequence diversity makes it difficult to determine the contribution of specific amino acid changes to pathology. Sequences of light chains associated with multiple myeloma provide a useful comparison to study mechanisms of light chain aggregation, but relatively few monoclonal sequences have been determined. Therefore, we sought to identify complete light chain sequences from existing high throughput sequencing data.MethodsWe developed a computational approach using the MiXCR suite of tools to extract complete rearranged IGVL-IGJL sequences from untargeted RNA sequencing data. This method was applied to whole-transcriptome RNA sequencing data from 766 newly diagnosed patients in the Multiple Myeloma Research Foundation CoMMpass study.ResultsMonoclonal IGVL-IGJL sequences were defined as those where >50% of assigned IGK or IGL reads from each sample mapped to a unique sequence. Clonal light chain sequences were identified in 705/766 samples from the CoMMpass study. Of these, 685 sequences covered the complete IGVL-IGJL region. The identity of the assigned sequences is consistent with their associated clinical data and with partial sequences previously determined from the same cohort of samples. Sequences have been deposited in AL-Base.DiscussionOur method allows routine identification of clonal antibody sequences from RNA sequencing data collected for gene expression studies. The sequences identified represent, to our knowledge, the largest collection of multiple myeloma-associated light chains reported to date. This work substantially increases the number of monoclonal light chains known to be associated with non-amyloid plasma cell disorders and will facilitate studies of light chain pathology.</p

On the resilience of Australian public universities: Why our institutions may fail unless vice-chancellors rethink broken commercial business models

COVID-19-related public health measures have severely impacted the Australian higher education system (AHES). This paper examines the resilience of the AHES, particularly its past reliance on onshore international students to generate revenue that cross-subsidises operational and research expenses. By our measure, ten universities are at risk of financial default. With a different approach on the part of the Government and university leadership, surplus monies could have contributed to building a more resilient AHES. Our findings correct widely held misconceptions about the state of the AHES and aim to provide valuable learnings to individual universities and the sector more broadly

Synthesis, Structures, and Photophysical Properties of Optically Stable 1,16-Diphenyl-3,14-diaryl-Substituted Tetrahydrobenzo[5]helicenediol Derivatives: Enantioselective Recognition toward Tryptophan Methyl Esters

Starting from commercially available 7-methoxytetralone, 1,16-diphenyl-3,14-dibromo­tetrahydro­benzo[5]­helicenediol (Br-H[5]­HOL) was conveniently prepared, which underwent efficient resolution to give the optically stable enantiomeric diols in gram scale by HPLC with semipreparative chiral columns. The absolute configurations of the diols were determined by the circular dichroism (CD) spectra and X-ray crystal structure. By Suzuki–Miyaura cross-coupling reactions, a series of enantiopure π-extended 1,16-diphenyl-3,14-diaryl­tetrahydro­benzo­[5]­helicenediol derivatives (Ar-H[5]­HOL) were further synthesized in high yields. The enantiomeric Ar-H[5]­HOL exhibited almost identical absorption and emission spectra but showed mirror-image CD spectra and mirror-image circularly polarized luminescence properties. Moreover, it was also found that aryl substituents at the 3,14-positions could extend the chiral environment of the helical skeletons, which led to efficient enantioselective recognition of the enantiomers of tryptophan methyl esters

Phage Predation Promotes Filamentous Bacterium <i>Piscinibacter</i> Colonization and Improves Structural and Hydraulic Stability of Microbial Aggregates

Although bacteria–phage interactions have broad environmental applications and ecological implications, the influence of phage predation on bacterial aggregation and structural stability remains largely unexplored. Herein, we demonstrate that inefficient lytic phage predation can promote host filamentous bacterium Piscinibacter colonization onto non-host Thauera aggregates, improving the structural and hydraulic stability of the dual-species aggregates. Specifically, phage predation at 103–104 PFU/mL (i.e., multiplication of infection at 0.01–0.1) promoted initial Piscinibacter colonization by 10–15 folds and resulted in 29–31% higher abundance of Piscinibacter in the stabilized aggregates than that in the control aggregates without phage predation. Transcriptomic analysis revealed upregulated genes related to quorum sensing (by 15–92 folds) and polysaccharide secretion (by 10–90 folds) within the treated aggregates, which was consistent with 120–172% higher content of polysaccharides for the treated dual-species aggregates. Confocal laser scanning microscopic images further confirmed the increase of filamentous bacteria and polysaccharides (both with wider distribution) within the dual-species aggregates. Accordlingly, the aggregates’ structural strength (via atomic force microscopes) and shear resistance (via hydraulic stress tests) increased by 77 and 42%, respectively, relative to the control group. In the long-term experiments, the enhanced hydraulic stability of the treated aggregates could facilitate dwelling bacteria propagation in flow-through conditions. Overall, our study demonstrates that phage predation can promote bacterial aggregation and enhance aggregate structural stability, revealing the beneficial role of lytic phage predation on bacterial symbiosis and environmental adaptivity

Detection of 5′ capping of the transcripts of <i>LUC</i>, <i>AtSOT12</i>, <i>At5g25280</i>, <i>COR15A</i>, and <i>COR47</i> in wild type, <i>shi1</i> and <i>shi4</i> mutants.

<p>(A) Relative capping ratios of the five selected genes transcripts determined by using the RLM-qRT-PCR method. Values are shown as mean ± SD (n = 3). (B) Percentages of the capped mRNA of three selected genes determined by using the 5′ RACE based method.</p

The Arabidopsis RNA Binding Protein with K Homology Motifs, SHINY1, Interacts with the C-terminal Domain Phosphatase-like 1 (CPL1) to Repress Stress-Inducible Gene Expression

<div><p>The phosphorylation state of the C-terminal domain (CTD) of the RNA polymerase II plays crucial roles in transcription and mRNA processing. Previous studies showed that the plant CTD phosphatase-like 1 (CPL1) dephosphorylates Ser-5-specific CTD and regulates abiotic stress response in Arabidopsis. Here, we report the identification of a K-homology domain-containing protein named SHINY1 (SHI1) that interacts with CPL1 to modulate gene expression. The <i>shi1</i> mutant was isolated from a forward genetic screening for mutants showing elevated expression of the luciferase reporter gene driven by a salt-inducible promoter. The <i>shi1</i> mutant is more sensitive to cold treatment during vegetative growth and insensitive to abscisic acid in seed germination, resembling the phenotypes of <i>shi4</i> that is allelic to the <i>cpl1</i> mutant. Both SHI1 and SHI4/CPL1 are nuclear-localized proteins. SHI1 interacts with SHI4/CPL1 <i>in vitro</i> and <i>in vivo</i>. Loss-of-function mutations in <i>shi1</i> and <i>shi4</i> resulted in similar changes in the expression of some stress-inducible genes. Moreover, both <i>shi1</i> and <i>shi4</i> mutants display higher mRNA capping efficiency and altered polyadenylation site selection for some of the stress-inducible genes, when compared with wild type. We propose that the SHI1-SHI4/CPL1 complex inhibits transcription by preventing mRNA capping and transition from transcription initiation to elongation.</p></div

Gene expression and subcellular localization of the SHI1.

<p>(A) Promoter-GUS analysis showing GUS expression at different developmental stages and different organs. (B) Northern blot showing the transcript levels of <i>SHI1</i> gene in different organs. (C) The subcellular localization of the SHI-GFP fusion protein. The left panel shows the nuclear localization of the fusion protein and the right panel shows fluorescent staining of the nucleus by Hoechst 33342. (D) Northern blot showing the <i>SHI1</i> gene expression in response to different abiotic stress treatments. Control, control without treatment; NaCl, 100 mM NaCl for 12 h; NaNO₃, 100 mM NaNO₃ for 12 h; KCl, 100 mM KCl for 12 h; LiCl, 100 mM LiCl for 12 h; Sorbitol, 200 mM sorbitol for 12 h; Cold, 4°C for 24 h; ABA, 100 µM ABA for 3 h; Desicc, desiccation for 15 min; pH 3.0, pH 3.0 for 12 h; pH 8.5, pH 8.5 for 12 h. Tubulin is shown as a loading control.</p

Synthesis, Structures, and Photophysical Properties of Optically Stable 1,16-Diphenyl-3,14-diaryl-Substituted Tetrahydrobenzo[5]helicenediol Derivatives: Enantioselective Recognition toward Tryptophan Methyl Esters

Starting from commercially available 7-methoxytetralone, 1,16-diphenyl-3,14-dibromo­tetrahydro­benzo[5]­helicenediol (Br-H[5]­HOL) was conveniently prepared, which underwent efficient resolution to give the optically stable enantiomeric diols in gram scale by HPLC with semipreparative chiral columns. The absolute configurations of the diols were determined by the circular dichroism (CD) spectra and X-ray crystal structure. By Suzuki–Miyaura cross-coupling reactions, a series of enantiopure π-extended 1,16-diphenyl-3,14-diaryl­tetrahydro­benzo­[5]­helicenediol derivatives (Ar-H[5]­HOL) were further synthesized in high yields. The enantiomeric Ar-H[5]­HOL exhibited almost identical absorption and emission spectra but showed mirror-image CD spectra and mirror-image circularly polarized luminescence properties. Moreover, it was also found that aryl substituents at the 3,14-positions could extend the chiral environment of the helical skeletons, which led to efficient enantioselective recognition of the enantiomers of tryptophan methyl esters

Map-based cloning and characterization of the <i>SHI4</i> locus.

<p>(A) Identification of the <i>shi4</i> mutation. (B) Hypersensitive phenotype of the <i>shi4</i> mutant to low temperature. (C) Subcellular localization of SHI4-GFP fusion protein. Showing is GFP fluorescence and merged image of GFP fluorescence in the root.</p

Occurrence and risk assessment of polycyclic aromatic hydrocarbons in the Hanjiang River Basin and the Danjiangkou Reservoir, China

<p>This study was conducted to investigate the occurrence, distribution, and source of 16 polycyclic aromatic hydrocarbons (PAHs) in the Hanjiang River Basin and the Danjiangkou (DJK) Reservoir. The concentrations of total PAHs in surface water, sediments, and bank soils ranged from 9.42 to 137.94 ng/l, 86.23 to 2514.93 ng/g, and 133.17 to 671.93 ng/g dry weight, respectively. The composition pattern of PAHs showed that 3-ring PAHs were dominated in all of the samples, while the proportion of high molecular weight PAHs (5- to 6-ring PAHs) in sediments and bank soil samples was almost three times higher than water. The source apportionment analysis showed that most of the PAHs in water were derived from sources of petroleum and combustion, while combustion was the predominant source of PAHs in sediments and bank soils. The methods based on toxic equivalency factors, risk quotient, and incremental lifetime cancer risk were used to assess the ecosystem risk and potential health risk of PAHs. The risk assessments showed that PAHs in the DJK Reservoir were out of potential health risk, but the ecological risk for majority of 16 PAHs was in the moderate level.</p