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Introductory biochemistry courses are often challenging for students because they require the integration of chemistry, biology, physics, math, and physiology knowledge and frameworks to understand and apply a large body of knowledge. This can be complicated by students' persistent misconceptions of fundamental concepts and lack of fluency with the extensive visual and symbolic literacy used in biochemistry. Card sorting tasks and game-based activities have been used to reveal insights into how students are assimilating, organizing, and structuring disciplinary knowledge, and how they are progressing along a continuum from disciplinary novice to expert. In this study, game-based activities and card sorting tasks were used to promote and evaluate students' understanding of fundamental structure-function relationships in biochemistry. Our results suggest that while many markers of expertise increased for both the control and intervention groups over the course of the semester, students involved in the intervention activities tended to move further towards expert-like sorting. This indicates that intentional visual literacy game-based activities have the ability to build underdeveloped skills in undergraduate students.

The article focuses on the reasons behind the rejection of papers submitted to the Journal of Mental Health, highlighting the increasing number of submissions and the rigorous review process. Topics include the importance of meeting submission criteria, considerations during the scientific evaluation process, and specific guidelines for different types of studies, such as prioritizing international importance and avoiding redundant research on topics like COVID-19.

Hsp90s are ATP-dependent chaperones that collaborate with co-chaperones and Hsp70s to remodel client proteins. Grp94 is the ER Hsp90 homolog essential for folding multiple secretory and membrane proteins. Grp94 interacts with the ER Hsp70, BiP, although the collaboration of the ER chaperones in protein remodeling is not well understood. Grp94 undergoes large-scale conformational changes that are coupled to chaperone activity. Within Grp94, a region called the pre-N domain suppresses ATP hydrolysis and conformational transitions to the active chaperone conformation. In this work, we combined in vivo and in vitro functional assays and structural studies to characterize the chaperone mechanism of Grp94. We show that Grp94 directly collaborates with the BiP chaperone system to fold clients. Grp94's pre-N domain is not necessary for Grp94-client interactions. The folding of some Grp94 clients does not require direct interactions between Grp94 and BiP in vivo, suggesting that the canonical collaboration may not be a general chaperone mechanism for Grp94. The BiP co-chaperone DnaJB11 promotes the interaction between Grp94 and BiP, relieving the pre-N domain suppression of Grp94's ATP hydrolysis activity. In structural studies, we find that ATP binding by Grp94 alters the ATP lid conformation, while BiP binding stabilizes a partially closed Grp94 intermediate. Together, BiP and ATP push Grp94 into the active closed conformation for client folding. We also find that nucleotide binding reduces Grp94's affinity for clients, which is important for productive client folding. Alteration of client affinity by nucleotide binding may be a conserved chaperone mechanism for a subset of ER chaperones. [ABSTRACT FROM AUTHOR]

As the urgency to limit global warming has intensified, negative emissions technology such as direct air capture and carbon sequestration are increasingly considered in climate mitigation scenarios. When Iceland opened the commercial-grade direct air carbon capture and storage (DACCS) facility in 2021, this marked a breakthrough for DACCS technology as a scalable climate mitigation solution. This study investigates the adoption of DACCS in Iceland and the potential for diffusion into other contexts as a global decarbonization solution. We implement expert interviews to analyze the adoption of technology, and to identify the various requirements of scaling DACCS into local and global contexts. Using inductive thematic analysis, we characterize the diverging perspectives on the role of carbon dioxide removal as a climate mitigation solution and also identify pathways toward technology upscaling at national, regional, and global scales. Despite the successful technology demonstration of DACCS, we find that experts hold different mental models of climate mitigation generally, characterized as "nature vs. technology." We also find that experts clearly articulate the necessary conditions for the diffusion of DACCS more broadly, including explicit regulatory measures as guardrails against a "license to pollute" as well as bilateral governance structures that include financial investment. Finally, we find that the importance of public acceptance of the technology was noted among all expert groups. Limited data exist on the acceptance of DACCS paired with renewable energy and this is a future research recommendation. [ABSTRACT FROM AUTHOR]

KCNQ1, the major component of the slow-delayed rectifier potassium channel, is responsible for repolarization of cardiac action potential. Mutations in this channel can lead to a variety of diseases, most notably long QT syndrome. It is currently unknown how many of these mutations change channel function and structure on a molecular level. Since tetramerization is key to proper function and structure of the channel, it is likely that mutations modify the stability of KCNQ1 oligomers. Presently, the C-terminal domain of KCNQ1 has been noted as the driving force for oligomer formation. However, truncated versions of this protein lacking the C-terminal domain still tetramerize. Therefore, we explored the role of native cysteine residues in a truncated construct of human KCNQ1, amino acids 100–370, by blocking potential interactions of cysteines with a nitroxide based spin label. Mobility of the spin labels was investigated with continuous wave electron paramagnetic resonance (CW-EPR) spectroscopy. The oligomerization state was examined by gel electrophoresis. The data provide information on tetramerization of human KCNQ1 without the C-terminal domain. Specifically, how blocking the side chains of native cysteines residues reduces oligomerization. A better understanding of tetramer formation could provide improved understanding of the molecular etiology of long QT syndrome and other diseases related to KCNQ1. • Exploration of oligomerization of Kv channels without C-terminal domain. • Nitroxide based spin labeling of native cysteine residues alters oligomerization. • C214 plays a role in the stability and or formation of KCNQ1 tetramers. [ABSTRACT FROM AUTHOR]

Extensive portions of the human genome have unknown function, including those derived from transposable elements. One such element, the DNA transposon Hsmar1, entered the primate lineage approximately 50 million years ago leaving behind terminal inverted repeat (TIR) sequences and a single intact copy of the Hsmar1 transposase, which retains its ancestral TIR-DNA-binding activity, and is fused with a lysine methyltransferase SET domain to constitute the chimeric SETMAR gene. Here, we provide a structural basis for recognition of TIRs by SETMAR and investigate the function of SETMAR through genome-wide approaches. As elucidated in our 2.37 Å crystal structure, SETMAR forms a dimeric complex with each DNA-binding domain bound specifically to TIRDNA through the formation of 32 hydrogen bonds. We found that SETMAR recognizes primarily TIR sequences (-5000 sites) within the human genome as assessed by chromatin immunoprecipitation sequencing analysis. In two SETMAR KO cell lines, we identified 163 shared differentially expressed genes and 233 shared alternative splicing events. Among these genes are several pre-mRNA-splicing factors, transcription factors, and genes associated with neuronal function, and one alternatively spliced primate-specific gene, TMEM14B, which has been identified as a marker for neocortex expansion associated with brain evolution. Taken together, our results suggest a model in which SETMAR impacts differential expression and alternative splicing of genes associated with transcription and neuronal function, potentially through both its TIR-specific DNA-binding and lysine methyltransferase activities, consistent with a role for SETMAR in simian primate development. [ABSTRACT FROM AUTHOR]

Introductory biochemistry courses are often challenging for students because they require the integration of chemistry, biology, physics, math, and physiology knowledge and frameworks to understand and apply a large body of knowledge. This can be complicated by students' persistent misconceptions of fundamental concepts and lack of fluency with the extensive visual and symbolic literacy used in biochemistry. Card sorting tasks and game‐based activities have been used to reveal insights into how students are assimilating, organizing, and structuring disciplinary knowledge, and how they are progressing along a continuum from disciplinary novice to expert. In this study, game‐based activities and card sorting tasks were used to promote and evaluate students' understanding of fundamental structure–function relationships in biochemistry. Our results suggest that while many markers of expertise increased for both the control and intervention groups over the course of the semester, students involved in the intervention activities tended to move further towards expert‐like sorting. This indicates that intentional visual literacy game‐based activities have the ability to build underdeveloped skills in undergraduate students. [ABSTRACT FROM AUTHOR]

The United States contributes only 0.2% of the 18,814 MW of global installed offshore wind capacity. Lack of development has been attributed in part to a cumbersome regulatory process that includes the evaluation of environmental impacts. Assessments are based on biological, social, and technical data that are often incomplete. Marine spatial planning (MSP) may help fill data gaps. We conducted semi-structured interviews with key informants to understand (1) whether a lack of biological data impedes offshore wind environmental assessments, (2) whether MSP could mitigate these impediments, and (3) whether MSP could advance offshore wind development in the U.S. in other ways. Most informants stated that a lack of biological data in offshore wind environmental assessments was problematic due to incomplete data, uncertainty of data, and mismatched scales. Data issues may be mitigated by creation of data products and increased communication, outcomes of MSP that may benefit the regulatory process by increasing data availability, resolving conflicts among users, and providing a common operating picture. Challenges remain in integrating MSP into the processes of siting and permitting offshore wind, but it provides a strategic framework for the systematic identification, collection, collation, analyses, application, and management of data in the offshore wind environmental regulatory process. [ABSTRACT FROM AUTHOR]

The VErtex LOcator (VELO) is the silicon microstrip vertexing and triggering sub-detector of the LHCb experiment. It consists of a series of forward disks with the active region ex- tending to just 8 mm from the LHC beams. The current status of the VELO is presented. Due to the high radiation environment, the VELO may have to be replaced after some years, possibly with new materials. A candidate material is Czochralski silicon. We present here promising new results on the first test beam of a large, high resistivity Czochralski microstrip silicon detector read out with LHC speed electronics. The performance was studied before and after irradiation with high energy protons. A signal to noise of over 20:1 was obtained from the detector and significant charge collection efficiencies were measured at relatively modest voltages after a fluence of 4.3 × 1014 1 MeV neutron equivalents (neq) per cm². Studies using the Transient Current Technique probed the electric field within MCz test detectors and proved that MCz silicon does not type invert up until a radiation level of at least 5 × 1014 24 GeV/c p/cm². This would mean the VELO could possibly replace, in a potential upgrade, n+ -on-n DOFZ sensors and the complicated processing involved, for standard p+ -on-n processing with MCz. [ABSTRACT FROM AUTHOR]

Telomere dysfunction has been strongly implicated in the initiation of genomic instability and is suspected to be an early event in the carcinogenesis of human solid tumors. Recent findings have established the presence of telomere fusions in human breast and prostate malignancies; however, the onset of this genomic instability mechanism during progression of other solid cancers is not well understood. Herein, we explored telomere dynamics in patient-derived epithelial ovarian cancers (OC), a malignancy characterized by multiple distinct subtypes, extensive molecular heterogeneity, and widespread genomic instability. We discovered a high frequency of telomere fusions in ovarian tumor tissues; however, limited telomere fusions were detected in normal adjacent tissues or benign ovarian samples. In addition, we found relatively high levels of both telomerase activity and hTERT expression, along with anaphase bridges in tumor tissues, which were notably absent in adjacent normal ovarian tissues and benign lesions. These results suggest that telomere dysfunction may occur early in ovarian carcinogenesis and, importantly, that it may play a critical role in the initiation and progression of the disease. Recognizing telomere dysfunction as a pervasive feature of this heterogeneous malignancy may facilitate the future development of novel diagnostic tools and improved methods of disease monitoring and treatment. [ABSTRACT FROM AUTHOR]

In mammalian cells, specific aminoacyl-transfer RNA (tRNA) synthetases have cytokine functions that require interactions with partners outside of the translation apparatus. Little is known about these interactions and how they facilitate expanded functions that link protein translation to other cellular pathways. For example, an alternative splice fragment of tryptophanyl-tRNA synthetase (TrpRS) and a similar natural proteolytic fragment are potent angiostatic factors that act through the vascular endothelial-cadherin receptor and Akt signaling pathway. Here we demonstrate mobilization of TrpRS for exocytosis from endothelial cells and the potential for plasmin to activate the cytokine function of the extracellular synthetase. Direct physical evidence showed that the annexin II-S100A10 complex, which regulates exocytosis, forms a ternary complex with TrpRS. Functional studies demonstrate that both annexin II and S100A10 regulate trafficking of TrpRS. Thus, complexes of mammalian tRNA synthetases with seemingly disparate proteins may in general be relevant to understanding how their expanded functions are implemented. [ABSTRACT FROM AUTHOR]

Summary: Disease-causing mutations occur in genes for aminoacyl tRNA synthetases. That some mutations are dominant suggests a gain of function. Native tRNA synthetases, such as tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase, catalyze aminoacylation and are also procytokines that are activated by natural fragmentation. In principle, however, gain-of-function phenotypes could arise from mutational activation of synthetase procytokines. From crystal structure analysis, we hypothesized that a steric block of a critical Glu-Leu-Arg (ELR) motif in full-length TyrRS suppresses the cytokine activity of a natural fragment. To test this hypothesis, we attempted to uncover ELR in the procytokine by mutating a conserved tyrosine (Y341) that tethers ELR. Site-specific proteolytic cleavage and small-angle X-ray scattering established subtle opening of the structure by the mutation. Strikingly, four different assays demonstrated mutational activation of cytokine functions. The results prove the possibilities for constitutive gain-of-function mutations in tRNA synthetases. [Copyright &y& Elsevier]

Native lipid bilayer mimetics, including those that use amphiphilic polymers, are important for the effective study of membrane-bound peptides and proteins. Copolymers of vinyl ether monomers and maleic anhydride were developed with controlled molecular weights and hydrophobicity through reversible addition-fragmentation chain-transfer polymerization. After polymerization, the maleic anhydride units can be hydrolyzed, giving dicarboxylates. The vinyl ether and maleic anhydride copolymerized in a close to alternating manner, giving essentially alternating hydrophilic maleic acid units and hydrophobic vinyl ether units along the backbone after hydrolysis. The vinyl ether monomers and maleic acid polymers self-assembled with lipids, giving vinyl ether maleic acid lipid particles (VEMALPs) with tunable sizes controlled by either the vinyl ether hydrophobicity or the polymer molecular weight. These VEMALPs were able to support membrane-bound proteins and peptides, creating a new class of lipid bilayer mimetics.

Extensive portions of the human genome have unknown function, including those derived from transposable elements. One such element, the DNA transposon Hsmar1, entered the primate lineage approximately 50 million years ago leaving behind terminal inverted repeat (TIR) sequences and a single intact copy of the Hsmar1 transposase, which retains its ancestral TIR-DNA-binding activity, and is fused with a lysine methyltransferase SET domain to constitute the chimeric SETMAR gene. Here, we provide a structural basis for recognition of TIRs by SETMAR and investigate the function of SETMAR through genome-wide approaches. As elucidated in our 2.37 Å crystal structure, SETMAR forms a dimeric complex with each DNA-binding domain bound specifically to TIR-DNA through the formation of 32 hydrogen bonds. We found that SETMAR recognizes primarily TIR sequences (∼5000 sites) within the human genome as assessed by chromatin immunoprecipitation sequencing analysis. In two SETMAR KO cell lines, we identified 163 shared differentially expressed genes and 233 shared alternative splicing events. Among these genes are several pre-mRNA-splicing factors, transcription factors, and genes associated with neuronal function, and one alternatively spliced primate-specific gene, TMEM14B, which has been identified as a marker for neocortex expansion associated with brain evolution. Taken together, our results suggest a model in which SETMAR impacts differential expression and alternative splicing of genes associated with transcription and neuronal function, potentially through both its TIR-specific DNA-binding and lysine methyltransferase activities, consistent with a role for SETMAR in simian primate development., Competing Interests: Conflict of interest R. C. W. has received grant support from Eli Lilly and Company, and R. C. W. serves as a scientific advisor to HiberCell; all other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)