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One of the most ubiquitous stabilizing forces in nature is the hydrogen bond, exemplified by the folded secondary, tertiary, and higher-order structure of biomolecules. Despite the fundamental importance of hydrogen bonding, dependence on this stabilizing force places limitations on nature's proteinogenic building blocks. Herein, we demonstrate that replacement of the strictly conserved glycine in collagen with aza-glycine has profound consequences on the stability and self-assembly of collagen peptides by providing an extra hydrogen bond donor. The additional hydrogen bond provided by aza-glycine allows for complete replacement of glycine residues in collagen peptides and truncation to the smallest self-assembling collagen peptide systems observed to date. Our results highlight the vital importance of hydrogen bonding at desolvated interfaces, providing a new strategy for optimization of designed peptide materials and a general solution for stabilizing the collagen triple helix.

Numerous American national committees have recommended the replacement of traditional labs with a more engaging curriculum that inspires inquiry and enhances scientific skills (examples include the President's Council of Advisors on Science and Technology (PCAST)'s Engage to Excel program and American Association for the Advancement of Science (AAAS) Vision and Change, among others), due to a large body of evidence that shows significant enhancements in student learning and affective outcomes. The implementation of Course-Based Undergraduate Research Experiences (CUREs) is a creative way to scale up the deployment of authentic research experiences to students. Another highly regarded high-impact practice in postsecondary education is the addition of learning communities. The integration of a three-course learning community and authentic research experiences to laboratory courses adds both a community of scholarship and a development of scientific communication and process skills. This study describes a course that blends these two high-impact practices in higher education in order to promote greater post-course gains in essential elements of a CURE curriculum. This collaborative course shows large post-course gains in essential elements, such as scientific communication and working collaboratively.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) 13C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule 13C-glycerol carbonate (13C-GLC), the post-dissolution reaction, and converting HP 13C-GLC to an injectable HP 13C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al.1.

Success in undergraduate chemical experiments requires students to develop knowledge and skills of instrumentation, equipment, and chemical techniques. In this technology report, we propose an adaptable and user-focused strategy to improve students' foundational skill and proficiency with chemical laboratory techniques and instrumentation. The strategy is composed of multiperspective filming of experimental activities using mobile phones or professional-level filming to create videos that can be freely viewed by students in situ during laboratory classes on a mobile device (iPad). Details of mixed digital approaches for a variety of chemical experimental techniques (10 examples) are compared with professional-level filming and mobile-phone filming. The results show that both the accuracy and precision of the developed videos are highly suitable for teaching purposes. Use of mobile-phone cameras permitted chemical techniques to be filmed from multiple angles in constrained spaces, such as fume hoods. A major benefit to students was the utility of the videos on portable devices, as students were informed by the video while setting up or performing the task at hand during laboratory sessions.

As part of the final year of their undergraduate degree programmes, some chemistry students at the University of Bristol spend time in local primary or secondary schools working on chemistry or chemical education problems. All partners gain from this programme. The students develop many of the transferable skills required by employers in all sectors. The scheme also provides them with the chance to gain some experience of working in schools, at the same time as acquiring credit as part of their degree programme. Many of the participating students go on to postgraduate teacher training courses and become committed and effective teachers. The schools benefit from having young enthusiastic science role models, assistance in the classroom and an opportunity to develop and run new projects. The scheme also helps the university department develop better links with neighbouring schools.

When learning with abstract and scientific multiple external representations (MERs), low prior knowledge learners are said to have difficulties in using these MERs to achieve conceptual understanding. Yet little is known about what these limitations precisely entail. In order to understand this, we presented 101 learners with low prior knowledge of abstract scientific MERs to see (a) how many, and what kind of ideas (propositions) learners remembered from these MERs and (b) what the impact of these ideas is on conceptual understanding of the content. Propositional analysis indicates that learners created flawed internal representations. The discussion analyses the potentials that the learners have in using abstract representations to increase their understanding of scientific information and possible effects of instruction.

Abstract Electrosynthetic reactions are performed in either custom‐made reactors that are developed and machined in‐house or commercially available systems that offer good reproducibility but come at a high cost. To bridge this divide between customizability and reproducibility, we have developed the Open‐ESyn, which is a suite of 3D‐printed components compatible with the popular ElectraSyn. This collection of parts increases the electrosynthesis that can be performed with the ElectraSyn, expanding, for example, the scale, temperature and the type of electrodes that can be used. The standardized reactor environment can be inexpensively recreated, thereby maintaining the reproducibility of the ElectraSyn ecosystem.

Essential properties for a Point of Use (POU) water filter include maintaining high removal capacity and rate, with excellent mechanical properties to withstand pressure drop. Herein, mechanically robust tri-composite polyamide 6/iron oxide nanoparticles/tetra-n-butylammonium bromide (PA6/α-Fe2O3/TBAB) nanofiber composite membranes were electrospun for phosphate (P) remediation, where the diameter and composition were tuned by controlling solution compositions and electrospinning conditions. Tri-composite composition and morphology affect phosphate uptake where the adsorption capacity followed Langmuir isotherm whereas the adsorption kinetics followed pseudo second order behavior. Mechanical properties (i.e., Young’s Modulus (E) and toughness) were significantly influenced by the composition and morphology of the tri-composite, as well. Although additional TBAB and iron oxide decreased toughness, there are optimum composition ranges which resulted in maximum Young’s Modulus. Of the synthesized nanofiber membranes, PA6/α-Fe2O3/TBAB nanofibers with 17% α-Fe2O3 and 2% TBAB showed excellent phosphate uptake capacity [i.e., 8.9 mg/g (52 mg of P/g of α-Fe2O3)] while it is bendable, stretchable, and able to plastically deform without fracturing (i.e., Young’s modulus of 2.06 × 108 Pa and Toughness of 1.35 × 106 J m−3). With concerns over the impact of P on water resources and the long-term availability of limited P resources, this tri-composite membrane is well suited for applications in both wastewater treatment and resource recovery.

Many students enrolled in university physics have little interest in the subject matter, a trend more pronounced in females. This study assesses students' conceptual understanding and interest during the electrochemistry unit of a physics course for nonphysics majors that was revised in light of consistently low ratings from its students. The intervention, designed to improve the tutorials in a large lecture-based physics course, improved interest in the topic for which the new tutorials were implemented. However, no effect was seen for conceptual understanding, and the gender gaps persisted. (Contains 2 tables.)

A large enrollment, instructor-centered chemistry course taught with science demonstrations was transformed into one that was more student-centered. Course survey and examination results revealed more positive perceptions of the benefits of demonstrations and greater content mastery for students in the modified course than for those in the traditional course. (Contains 2 figures and 3 tables.)

The history of the development of mass spectroscopic methods used to characterize polymers is discussed. The continued improvements in methods and instrumentation will offer new and better ways for the mass spectral characterization of polymers and mass spectroscopy (MS) should be recognized as a complementary polymer characterization method along with size exclusion chromatography (SEC) and nuclear magnetic resonance (NMR).

The development of XPS as an effective method for surface analysis during the period 1964-1977 is presented. The study shows that unlike other surface methods, XPS data can be obtained for both conductors and insulators and a variety of samples can be handled effectively, which is one of the major reasons for the popularity of the technique.

Absences from school present a major obstacle to students gaining understanding of concepts developed in class. Investigates an alternative procedure for making up missed class work: viewing a quasi-interactive videotaped presentation of missed portions of a learning cycle in chemistry. (Author/SAH)

Self-assembly of peptide building blocks offers unique opportunities for bottom-up preparation of exquisite nanostructures, nanoarchitectures, and nanostructured bulk materials, namely hydrogels. In this work we describe the synthesis, characterization, gelation, and rheological properties of new dehydrotripeptides, Cbz-L-Lys(Cbz)-L,D-Asp-∆Phe-OH and (2-Naph)-L-Lys(2-Naph)-L,D-Asp-∆Phe-OH, containing a N-terminal lysine residue Nα,ε-bis-capped with carboxybenzyl (Cbz) and 2-Naphthylacetyl (2-Naph) aromatic moieties, an aspartic acid residue (Asp), and a C-terminal dehydrophenylalanine (∆Phe) residue. The dehydrotripeptides were obtained as diastereomeric mixtures (L,L,Z and L,D,Z), presumably via aspartimide chemistry. The dehydrotripeptides afforded hydrogels at exceedingly low concentrations (0.1 and 0.04 wt%). The hydrogels revealed exceptional elasticity (G’ = 5.44 × 104 and 3.43 × 106 Pa) and self-healing properties. STEM studies showed that the diastereomers of the Cbz-capped peptide undergo co-assembly, generating a fibrillar 3D network, while the diastereomers of the 2-Naph-capped dehydropeptide seem to undergo self-sorting, originating a fibril network with embedded spheroidal nanostructures. The 2-Naph-capped hydrogel displayed full fast recovery following breakup by a mechanical stimulus. Spheroidal nanostructures are absent in the recovered hydrogel, as seen by STEM, suggesting that the mechanical stimulus triggers rearrangement of the spheroidal nanostructures into fibers. Overall, this study demonstrates that diastereomeric mixtures of peptides can be efficacious gelators. Importantly, these results suggest that the structure (size, aromaticity) of the capping group can have a directing effect on the self-assembly (co-assembly vs. self-sorting) of diastereomers. The cytotoxicity of the newly synthesized gelators was evaluated using human keratinocytes (HaCaT cell line). The results indicated that the two gelators exhibited some cytotoxicity, having a small impact on cell viability. In sustained release experiments, the influence of the charge on model drug compounds was assessed in relation to their release rate from the hydrogel matrix. The hydrogels demonstrated sustained release for methyl orange (anionic), while methylene blue (cationic) was retained within the network.

We present a new laboratory experiment on the photochemistry of organometallic [eta][superscript 5],[eta][superscript 6]-mixed-sandwich compounds, which is suitable for both the physical chemistry and inorganic chemistry laboratory. Specifically, students use 1,10-phenanthroline to trap the intermediate formed when [CpFe(isopropylbenzene)]PF[subscript 6] is photolyzed with 458 nm light from an argon-krypton laser. Using quantitative UV-vis spectroscopy students then determine the quantum yield of arene ring displacement from the mixed-sandwich complex. The photogenerated intermediate, [CpFe(solvent)[subscript 3]][superscript +] is an efficient initiator for the polymerization of epoxides, dicyanate esters, pyrrole, styrene, dioxolenes, and acrylates. The efficiency with which the intermediate is photochemically formed is therefore an important property in determining its commercial utility. Although the experiment can easily be done in one 3-4 hour laboratory period, it readily lends itself to broadening into a multi-week research project. In this mode, students can examine how changing the nature of the solvent and the irradiation wavelength affect the quantum yield of reaction. Such information can be used to reveal the role of the solvent in the reaction and the electronic excited states from which reaction occurs. Furthermore, in the inorganic laboratory, students could be asked to synthesize [CpFe(isopropylbenzene]PF[subscript 6] before looking at its photochemical behavior, thus gaining experience in working under air-free conditions. (Contains 1 scheme, 2 figures and 1 table.)

Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer’s disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.75 Gy five-ion GCRsim or 2 Gy gamma radiation (IRR) in 14-month-old female and male APPNL-F/NL-F knock-in (KI) mice bearing humanized ApoE3 or ApoE4 (APP;E3F and APP;E4F). As travel to a specialized facility was required for irradiation, both traveled sham-irradiated C57BL/6J WT and KI mice and non-traveled (NT) KI mice acted as controls for potential effects of travel. Mice underwent four behavioral tests at 20 months of age and were euthanized for pathological and biochemical analyses 1 month later. Fecal samples were collected pre- and post-irradiation at four different time points. GCRsim seemed to impair memory in male APP;E3F mice compared to their sham counterparts. Travel tended to improve cognition in male APP;E3F mice and lowered total Aβ in female and male APP;E3F mice compared to their non-traveled counterparts. Sham-irradiated male APP;E4F mice accumulated more fibrillar amyloid than their APP;E3F counterparts. Radiation exposure had only modest effects on behavior and brain changes, but travel-, sex-, and genotype-specific effects were seen. Irradiated mice had immediate and long-term differences in their gut bacterial composition that correlated to Alzheimer’s disease phenotypes.

Photochemical sealing of a nerve wrap over the repair site isolates and optimizes the regenerating nerve microenvironment. To facilitate clinical adoption of the technology, we investigated photosealed autologous tissue in a rodent sciatic nerve transection and repair model. Rats underwent transection of the sciatic nerve with repair performed in three groups: standard microsurgical neurorrhaphy (SN) and photochemical sealing with a crosslinked human amnion (xHAM) or autologous vein. Functional recovery was assessed at four-week intervals using footprint analysis. Gastrocnemius muscle mass preservation, histology, and nerve histomorphometry were evaluated at 120 days. Nerves treated with a PTB-sealed autologous vein improved functional recovery at 120 days although the comparison between groups was not significantly different (SN: −58.4 +/− 10.9; XHAM: −57.9 +/− 8.7; Vein: −52.4 +/− 17.1). Good muscle mass preservation was observed in all groups, with no statistical differences between groups (SN: 69 +/− 7%; XHAM: 70 +/− 7%; Vein: 70 +/− 7%). Histomorphometry showed good axonal regeneration in all repair techniques. These results demonstrate that peripheral nerve repair using photosealed autologous veins produced regeneration at least equivalent to current gold-standard microsurgery. The use of autologous veins removes costs and foreign body concerns and would be readily available during surgery. This study illustrates a new repair method that could restore normal endoneurial homeostasis with minimal trauma following severe nerve injury.

Decades of research have identified genetic and environmental factors involved in age-related neurodegenerative diseases and, to a lesser extent, neuropsychiatric disorders. Genomic instability, i.e., the loss of genome integrity, is a common feature among both neurodegenerative (mayo-trophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease) and psychiatric (schizophrenia, autism, bipolar depression) disorders. Genomic instability is associated with the accumulation of persistent DNA damage and the activation of DNA damage response (DDR) pathways, as well as pathologic neuronal cell loss or senescence. Typically, DDR signaling ensures that genomic and proteomic homeostasis are maintained in both dividing cells, including neural progenitors, and post-mitotic neurons. However, dysregulation of these protective responses, in part due to aging or environmental insults, contributes to the progressive development of neurodegenerative and/or psychiatric disorders. In this Special Issue, we introduce and highlight the overlap between neurodegenerative diseases and neuropsychiatric disorders, as well as the emerging clinical, genomic, and molecular evidence for the contributions of DNA damage and aberrant DNA repair. Our goal is to illuminate the importance of this subject to uncover possible treatment and prevention strategies for relevant devastating brain diseases.

Arc (also known as Arg3.1) is an activity-dependent immediate early gene product enriched in neuronal dendrites. Arc plays essential roles in long-term potentiation, long-term depression, and synaptic scaling. Although its mechanisms of action in these forms of synaptic plasticity are not completely well established, the activities of Arc include the remodeling of the actin cytoskeleton, the facilitation of AMPA receptor (AMPAR) endocytosis, and the regulation of the transcription of AMPAR subunits. In addition, Arc has sequence and structural similarity to retroviral Gag proteins and self-associates into virus-like particles that encapsulate mRNA and perhaps other cargo for intercellular transport. Each of these activities is likely to be influenced by Arc’s reversible self-association into multiple oligomeric species. Here, we used mass photometry to show that Arc exists predominantly as monomers, dimers, and trimers at approximately 20 nM concentration in vitro. Fluorescence fluctuation spectroscopy revealed that Arc is almost exclusively present as low-order (monomer to tetramer) oligomers in the cytoplasm of living cells, over a 200 nM to 5 μM concentration range. We also confirmed that an α-helical segment in the N-terminal domain contains essential determinants of Arc’s self-association.

Inflammation and oxidative stress are implicated in the pathogenesis of Crohn’s disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn’s disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn’s colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril’s effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42–0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.

Activity-regulated cytoskeleton-associated protein (Arc) plays essential roles in diverse forms of synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and homeostatic plasticity. In addition, it assembles into virus-like particles that may deliver mRNAs and/or other cargo between neurons and neighboring cells. Considering this broad range of activities, it is not surprising that Arc is subject to regulation by multiple types of post-translational modification, including phosphorylation, palmitoylation, SUMOylation, ubiquitylation, and acetylation. Here we explore the potential regulatory role of Arc phosphorylation by protein kinase C (PKC), which occurs on serines 84 and 90 within an α-helical segment in the N-terminal domain. To mimic the effect of PKC phosphorylation, we mutated the two serines to negatively charged glutamic acid. A consequence of introducing these phosphomimetic mutations is the almost complete inhibition of Arc palmitoylation, which occurs on nearby cysteines and contributes to synaptic weakening. The mutations also inhibit the binding of nucleic acids and destabilize high-order Arc oligomers. Thus, PKC phosphorylation of Arc may limit the full expression of LTD and may suppress the interneuronal transport of mRNAs.

Historical coal mining practices have caused various soil and water hazards, particularly through the dumping of mine waste. The primary environmental risk associated with this waste is the leaching of toxic metals from dumps of spoil or refuse into the subsurface soil or into nearby water resources. The extent of metal release is controlled via the oxidative dissolution of pyrite and potential re-sequestration through secondary Fe oxides. The characterization of the dominant Fe-bearing phase and the distribution of trace metals associated with these phases was determined via electron microscopy, synchrotron-based X-ray micro-fluorescence (μ-XRF) element and redox mapping from shallow mine soils from an impacted watershed in Appalachian Ohio. The dominant Fe-bearing phases were: (1) unweathered to partially weathered pyrite; (2) pseudomorphic replacement of pyrite with Fe(III) oxides; (3) fine-grained Fe oxide surface coatings; and (4) discrete Fe(III) oxide grains. Thicker secondary coatings and larger particles were sulfate rich, whereas smaller grains and thinner coatings were sulfate poor. The discrete Fe oxide grains exhibited the highest concentrations of Cr, Mn, Ni, and Cu, and sub-grain-scale concentration trends (Mn > Cr > Ni > Cu) were consistent with bulk soil properties. Predicting future metal transport requires an understanding of metal speciation and distribution from the sub-grain scale to the pedon scale.

The ability to quickly discover reliable hits from screening and rapidly convert them into lead compounds, which can be verified in functional assays, is central to drug discovery. The expedited validation of novel targets and the identification of modulators to advance to preclinical studies can significantly increase drug development success. Our SaXPyTM (“SAR by X-ray Poses Quickly”) platform, which is applicable to any X-ray crystallography-enabled drug target, couples the established methods of protein X-ray crystallography and fragment-based drug discovery (FBDD) with advanced computational and medicinal chemistry to deliver small molecule modulators or targeted protein degradation ligands in a short timeframe. Our approach, especially for elusive or “undruggable” targets, allows for (i) hit generation; (ii) the mapping of protein–ligand interactions; (iii) the assessment of target ligandability; (iv) the discovery of novel and potential allosteric binding sites; and (v) hit-to-lead execution. These advances inform chemical tractability and downstream biology and generate novel intellectual property. We describe here the application of SaXPy in the discovery and development of DNA damage response inhibitors against DNA polymerase eta (Pol η or POLH) and apurinic/apyrimidinic endonuclease 1 (APE1 or APEX1). Notably, our SaXPy platform allowed us to solve the first crystal structures of these proteins bound to small molecules and to discover novel binding sites for each target.

A comprehensive project in which the students use computational chemistry to investigate a larger chlorine oxide, Cl2O4 is described. The students start the project by reading a scenario and then follow a series of hyperlinks to develop, along with their colleagues, a better understanding of the implications of the presence of Cl2O4 in the atmosphere.

Undergraduate research is an important learning experience for students and at small teaching-centered institutions with limited resources, research opportunities on campus can be insufficient to accommodate all interested students. However, to encourage these students to apply for such opportunities, a model that involves establishing partnership with a research-intensive school is developed.

Describes a computer simulation which deals with the Werner-Jorgensen controversy from the standpoint of Kuhn's description of scientific change. Encourages the use of such instructional approaches to introduce general chemistry students to the process of science, including how (1) theories develop, (2) change occurs, and (3) scientists behave. (TW)