Tailoring Hierarchical Structure and Rare Earth Affinity of Compositionally Identical Polymers via Sequence Control.

Macromolecule sequence, structure, and function are inherently intertwined. While well-established relationships exist in proteins, they are more challenging to define for synthetic polymer nanoparticles due to their molecular weight, sequence, and conformational dispersities. To explore the impact of sequence on nanoparticle structure, we synthesized a set of 16 compositionally identical, sequence-controlled polymers with distinct monomer patterning of dimethyl acrylamide and a bioinspired, structure-driving di(phenylalanine) acrylamide (FF). Sequence control was achieved through multiblock polymerizations, yielding unique ensembles of polymer sequences which were simulated by kinetic Monte Carlo simulations. Systematic analysis of the global (tertiary- and quaternary-like) structure in this amphiphilic copolymer series revealed the effect of multiple sequence descriptors: the number of domains, the hydropathy of terminal domains, and the patchiness (density) of FF within a domain, each of which impacted both chain collapse and the distribution of single- and multichain assemblies. Furthermore, both the conformational freedom of chain segments and local-scale, ß-sheet-like interactions were sensitive to the patchiness of FF. To connect sequence, structure, and target function, we evaluated an additional series of nine sequence-controlled copolymers as sequestrants for rare earth elements (REEs) by incorporating a functional acrylic acid monomer into select polymer scaffolds. We identified key sequence variables that influence the binding affinity, capacity, and selectivity of the polymers for REEs. Collectively, these results highlight the potential of and boundaries of sequence control via multiblock polymerizations to drive primary sequence ensembles hierarchical structures, and ultimately the functionality of compositionally identical polymeric materials.

Leveraging Triphenylphosphine-Containing Polymers to Explore Design Principles for Protein-Mimetic Catalysts.

Complex interactions between noncoordinating residues are significant yet commonly overlooked components of macromolecular catalyst function. While these interactions have been demonstrated to impact binding affinities and catalytic rates in metalloenzymes, the roles of similar structural elements in synthetic polymeric catalysts remain underexplored. Using a model Suzuki-Miyuara cross-coupling reaction, we performed a series of systematic studies to probe the interconnected effects of metal-ligand cross-links, electrostatic interactions, and local rigidity in polymer catalysts. To achieve this, a novel bifunctional triphenylphosphine acrylamide (BisTPPAm) monomer was synthesized and evaluated alongside an analogous monofunctional triphenylphosphine acrylamide (TPPAm). In model copolymer catalysts, increased initial reaction rates were observed for copolymers untethered by Pd complexation (BisTPPAm-containing) compared to Pd-cross-linked catalysts (TPPAm-containing). Further, incorporating local rigidity through secondary structure-like and electrostatic interactions revealed nonmonotonic relationships between composition and the reaction rate, demonstrating the potential for tunable behavior through secondary-sphere interactions. Finally, through rigorous cheminformatics featurization strategies and statistical modeling, we quantitated relationships between chemical descriptors of the substrate and reaction conditions on catalytic performance. Collectively, these results provide insights into relationships among the composition, structure, and function of protein-mimetic catalytic copolymers.

Family experiences reported by healthcare worker parents during the COVID-19 pandemic.

PURPOSE: Parents, who were working as essential frontline healthcare workers experienced unique stressors during the COVID-19 pandemic including disruption of regular routines, long lapses away from family, extreme work stress and subsequent difficulty in compartmentalizing work-related concerns when at home. The purpose of this study was to assess COVID-19 exposure and impact of frontline healthcare workers who are parents. DESIGN & METHODS: This study quantitatively assessed the COVID-19 exposure and impact and qualitatively explored perceptions of parents of children 9 to 17 years of age, who were also frontline healthcare workers. RESULTS: Participants (N = 79) using the COVID-19 Exposure and Family Impact Survey (CEFIS) reported exposure mean scores of 10.03 (SD = 2.63); and impact scores mean scores of 3.18 (SD = 0.46). Thematic analysis identified four themes, each with 2 subthemes: 1) family stressors increased (e.g., concerns about health and safety, losses of lifestyle patterns); 2) changes in children's health and well-being (e.g., isolation from family and friends, mental health problems); 3) virtual school difficulties (e.g., parent and student challenges, home school option); 4) skill building opportunities (e.g., enhanced emotional connections, increased family activities). CONCLUSION: The CHAMPS Family Health Study suggests that families of essential workers are especially vulnerable to the effect of COVID-19, as are those families of essential workers who include child/ren with special health care needs. PRACTICE IMPLICATIONS: Preparation for future emergencies requires strategies to mitigate consequences and promote well-being. These results highlight the need for supportive approaches to decrease the negative consequences of stress and to augment skills for family connection and cooperation.

Investigating Fundamental Principles of Nonequilibrium Assembly Using Temperature-Sensitive Copolymers.

Both natural biomaterials and synthetic materials benefit from complex energy landscapes that provide the foundation for structure-function relationships and environmental sensitivity. Understanding these nonequilibrium dynamics is important for the development of design principles to harness this behavior. Using a model system of poly(ethylene glycol) methacrylate-based thermoresponsive lower critical solution temperature (LCST) copolymers, we explored the impact of composition and stimulus path on nonequilibrium thermal hysteretic behavior. Through turbidimetry analysis of nonsuperimposable heat-cool cycles, we observe that LCST copolymers show clear hysteresis that varies as a function of pendent side chain length and hydrophobicity. Hysteresis is further impacted by the temperature ramp rate, as insoluble states can be kinetically trapped under optimized temperature protocols. This systematic study brings to light fundamental principles that can enable the harnessing of out-of-equilibrium effects in synthetic soft materials.

Versatile Triphenylphosphine-Containing Polymeric Catalysts and Elucidation of Structure-Function Relationships.

Synthetic polymers are a modular solution to bridging the two most common classes of catalysts: proteins and small molecules. Polymers offer the synthetic versatility of small-molecule catalysts while simultaneously having the ability to construct microenvironments mimicking those of natural proteins. We synthesized a panel of polymeric catalysts containing a novel triphenylphosphine acrylamide monomer and investigated how their properties impact the rate of a model Suzuki-Miyaura cross-coupling reaction. Systematic variation of polymer properties, such as the molecular weight, functional density, and comonomer identity, led to tunable reaction rates and solvent compatibility, including full conversion in an aqueous medium. Studies with bulkier substrates revealed connections between polymer parameters and reaction conditions that were further elucidated with a regression analysis. Some connections were substrate-specific, highlighting the value of the rapidly tunable polymer catalyst. Collectively, these results aid in building structure-function relationships to guide the development of polymer catalysts with tunable substrates and environmental compatibility.

Mapping the Morphological Landscape of Oligomeric Di-block Peptide-Polymer Amphiphiles.

Peptide-polymer amphiphiles (PPAs) are tunable hybrid materials that achieve complex assembly landscapes by combining the sequence-dependent properties of peptides with the structural diversity of polymers. Despite their promise as biomimetic materials, determining how polymer and peptide properties simultaneously affect PPA self-assembly remains challenging. We herein present a systematic study of PPA structure-assembly relationships. PPAs containing oligo(ethyl acrylate) and random-coil peptides were used to determine the role of oligomer molecular weight, dispersity, peptide length, and charge density on self-assembly. We observed that PPAs predominantly formed spheres rather than anisotropic particles. Oligomer molecular weight and peptide hydrophilicity dictated morphology, while dispersity and peptide charge affected particle size. These key benchmarks will facilitate the rational design of PPAs that expand the scope of biomimetic functionality within assembled soft materials.

Controlling Amphiphilic Polymer Folding beyond the Primary Structure with Protein-Mimetic Di(Phenylalanine).

While methods for polymer synthesis have proliferated, their functionality pales in comparison to natural biopolymers-strategies are limited for building the intricate network of noncovalent interactions necessary to elicit complex, protein-like functions. Using a bioinspired di(phenylalanine) acrylamide (FF) monomer, we explored the impact of various noncovalent interactions in generating ordered assembled structures. Amphiphilic copolymers were synthesized that exhibit ß-sheet-like local structure upon collapsing into single-chain assemblies in aqueous environments. Systematic analysis of a series of amphiphilic copolymers illustrated that the global collapse is primarily driven by hydrophobic forces. Hydrogen-bonding and aromatic interactions stabilize local structure, as ß-sheet-like interactions were identified via circular dichroism and thioflavin T fluorescence. Similar analysis of phenylalanine (F) and alanine-phenylalanine acrylamide (AF) copolymers found that distancing the aromatic residue from the polymer backbone is sufficient to induce ß-sheet-like local structure akin to the FF copolymers; however, the interactions between AF subunits are less stable than those formed by FF. Further, hydrogen-bond donating hydrophilic monomers disrupt internal structure formed by FF within collapsed assemblies. Collectively, these results illuminate design principles for the facile incorporation of multiple facets of protein-mimetic, higher-order structure within folded synthetic polymers.

DNA-Inspired Strand-Exchange for Switchable PMMA-Based Supramolecular Morphologies.

Inspired by nanotechnologies based on DNA strand displacement, herein we demonstrate that synthetic helical strand exchange can be achieved through tuning of poly(methyl methacrylate) (PMMA) triple-helix stereocomplexes. To evaluate the utility and robustness of helical strand exchange, stereoregular PMMA/polyethylene glycol (PEG) block copolymers capable of undergoing crystallization driven self-assembly via stereocomplex formation were prepared. Micelles with spherical or wormlike morphologies were formed by varying the molecular weight composition of the assembling components. Significantly, PMMA strand exchange was demonstrated and utilized to reversibly switch the micelles between different morphologies. This concept of strand exchange with PMMA-based triple-helix stereocomplexes offers new opportunities to program dynamic behaviors of polymeric materials, leading to scalable synthesis of "smart" nanosystems.

Control of Amphiphile Self-Assembly via Bioinspired Metal Ion Coordination.

Inspired by marine siderophores that exhibit a morphological shift upon metal coordination, hybrid peptide-polymer conjugates that assemble into different morphologies based on the nature of the metal ion coordination have been designed. Coupling of a peptide chelator, hexahistidine, with hydrophobic oligostyrene allows a modular strategy to be established for the efficient synthesis and purification of these tunable amphiphiles (oSt(His)6). Remarkably, in the presence of different divalent transition metal ions (Mn, Co, Ni, Cu, Zn, and Cd) a variety of morphologies were observed. Zinc(II), cobalt(II), and copper(II) led to aggregated micelles. Nickel(II) and cadmium(II) produced micelles, and multilamellar vesicles were obtained in the presence of manganese(II). This work highlights the significant potential for transition metal ion coordination as a tool for directing the assembly of synthetic nanomaterials.

Controlled Formation and Binding Selectivity of Discrete Oligo(methyl methacrylate) Stereocomplexes.

The triple-helix stereocomplex of poly(methyl methacrylate) (PMMA) is a unique example of a multistranded synthetic helix that has significant utility and promise in materials science and nanotechnology. To gain a fundamental understanding of the underlying assembly process, discrete stereoregular oligomer libraries were prepared by combining stereospecific polymerization techniques with automated flash chromatography purification. Stereocomplex assembly of these discrete building blocks enabled the identification of (1) the minimum degree of polymerization required for the stereocomplex formation and (2) the dependence of the helix crystallization mode on the length of assembling precursors. More significantly, our experiments resolved binding selectivity between helical strands with similar molecular weights. This presents new opportunities for the development of next-generation polymeric materials based on a triple-helix motif.

Evidence on public health interventions in humanitarian crises.

Recognition of the need for evidence-based interventions to help to improve the effectiveness and efficiency of humanitarian responses has been increasing. However, little is known about the breadth and quality of evidence on health interventions in humanitarian crises. We describe the findings of a systematic review with the aim of examining the quantity and quality of evidence on public health interventions in humanitarian crises to identify key research gaps. We identified 345 studies published between 1980 and 2014 that met our inclusion criteria. The quantity of evidence varied substantially by health topic, from communicable diseases (n=131), nutrition (n=77), to non-communicable diseases (n=8), and water, sanitation, and hygiene (n=6). We observed common study design and weaknesses in the methods, which substantially reduced the ability to determine causation and attribution of the interventions. Considering the major increase in health-related humanitarian activities in the past three decades and calls for a stronger evidence base, this paper highlights the limited quantity and quality of health intervention research in humanitarian contexts and supports calls to scale up this research.

A Versatile and Highly Selective Colorimetric Sensor for the Detection of Amines.

The utility of Meldrum's activated furan (MAF) for the colorimetric detection of sub ppm levels of amines in solution, on solid supports, and as vapors is reported. MAF is synthesized in one step from inexpensive and commercially available starting materials and exhibits high selectivity for primary and secondary amines in the presence of competing nucleophiles. The reaction between activated furans and amines results in a distinct color change, discernable by the naked eye. UV/Vis absorption spectroscopy was utilized to monitor reactions in solution and determine detection limits. Additionally, solutions of MAF were useful as stains for thin layer chromatography and for monitoring solid-phase synthesis of peptides and peptidomimetics. Finally, MAF was used to detect volatile amines released from fish samples, demonstrating potential for food spoilage applications.

A Versatile and Scalable Strategy to Discrete Oligomers.

A versatile strategy is reported for the multigram synthesis of discrete oligomers from commercially available monomer families, e.g., acrylates, styrenics, and siloxanes. Central to this strategy is the identification of reproducible procedures for the separation of oligomer mixtures using automated flash chromatography systems with the effectiveness of this approach demonstrated through the multigram preparation of discrete oligomer libraries (D = 1.0). Synthetic availability, coupled with accurate structural control, allows these functional building blocks to be harnessed for both fundamental studies as well as targeted technological applications.

Dynamic Implications of Noncovalent Interactions in Amphiphilic Single-Chain Polymer Nanoparticles.

Single-chain polymer nanoparticles (SCNPs) combine the chemical diversity of synthetic polymers with the intricate structure of biopolymers, generating versatile biomimetic materials. The mobility of polymer chain segments at length scales similar to secondary structural elements in proteins is critical to SCNP structure and thus function. However, the influence of noncovalent interactions used to form SCNPs (e.g., hydrogen-bonding and biomimetic secondary-like structure) on these conformational dynamics is challenging to quantitatively assess. To isolate the effects of noncovalent interactions on SCNP structure and conformational dynamics, we synthesized a series of amphiphilic copolymers containing dimethylacrylamide and monomers capable of forming these different interactions: (1) di(phenylalanine) acrylamide that forms intramolecular ß-sheet-like cross-links, (2) phenylalanine acrylamide that forms hydrogen-bonds but lacks a defined local structure, and (3) benzyl acrylamide that has the lowest propensity for hydrogen-bonding. Each SCNP formed folded structures comparable to those of intrinsically disordered proteins, as observed by size exclusion chromatography and small angle neutron scattering. The dynamics of these polymers, as characterized by a combination of dynamic light scattering and neutron spin echo spectroscopy, was well described using the Zimm with internal friction (ZIF) model, highlighting the role of each noncovalent interaction to additively restrict the internal relaxations of SCNPs. These results demonstrate the utility of local scale interactions to control SCNP polymer dynamics, guiding the design of functional biomimetic materials with refined binding sites and tunable kinetics.

Selective chromium(VI) ligands identified using combinatorial peptoid libraries.

Hexavalent chromium [Cr(VI)] is a worldwide water contaminant that is currently without cost-effective and efficient remediation strategies. This is in part due to a lack of ligands that can bind it amid an excess of innocuous ions in aqueous solution. We present herein the design and application of a peptoid-based library of ligand candidates for toxic metal ions. A selective screening process was used to identify members of the library that can bind to Cr(VI) species at neutral pH and in the presence of a large excess of spectator ions. There were 11 sequences identified, and their affinities were compared using titrations monitored with UV-vis spectroscopy. To identify the interactions involved in coordination and specificity, we evaluated the effects of sequence substitutions and backbone variation in the highest affinity structure. Additional characterization of the complex formed between this sequence and Cr(VI) was performed using NMR spectroscopy. To evaluate the ability of the developed sequences to remediate contaminated solutions, the structures were synthesized on a solid-phase resin and incubated with environmental water samples that contained simulated levels of chromium contamination. The synthetic structures demonstrated the ability to reduce the amount of toxic chromium to levels within the range of the EPA contamination guidelines. In addition to providing some of the first selective ligands for Cr(VI), these studies highlight the promise of peptoid sequences as easily prepared components of environmental remediation materials.

Navigating the Expansive Landscapes of Soft Materials: A User Guide for High-Throughput Workflows.

Synthetic polymers are highly customizable with tailored structures and functionality, yet this versatility generates challenges in the design of advanced materials due to the size and complexity of the design space. Thus, exploration and optimization of polymer properties using combinatorial libraries has become increasingly common, which requires careful selection of synthetic strategies, characterization techniques, and rapid processing workflows to obtain fundamental principles from these large data sets. Herein, we provide guidelines for strategic design of macromolecule libraries and workflows to efficiently navigate these high-dimensional design spaces. We describe synthetic methods for multiple library sizes and structures as well as characterization methods to rapidly generate data sets, including tools that can be adapted from biological workflows. We further highlight relevant insights from statistics and machine learning to aid in data featurization, representation, and analysis. This Perspective acts as a "user guide" for researchers interested in leveraging high-throughput screening toward the design of multifunctional polymers and predictive modeling of structure-property relationships in soft materials.

Infant fearful distress, parent intrusiveness, and adversity in families experiencing homelessness.

Infants experiencing homelessness face risk for developing mental health problems in the future. Parents residing in shelters experience adverse events at elevated rates compared to non-homeless individuals, which can impact their infants during a time of rapid development depending on how the parent copes. For some, trauma linked to these events may manifest in an intrusive parenting style that interferes with the child's developing capacity for self-regulation. We utilized a sample of 60 parent-infant dyads recruited while residing in emergency homeless shelters to evaluate associations among parents' history of adversity, intrusive parenting behaviors, and infants' fearful distress. Observed parent intrusiveness during a free play interaction was significantly associated with infant fearfulness observed in a separate behavioral task during which infants viewed a series of masks. Furthermore, there was a moderating effect for parent history of adversity such that the association between parent intrusiveness and infant fearful distress was stronger among parents with more past experiences of adversity.

Sci-athon: Promoting Interdisciplinary Science and Peer Learning with Adrenaline and Pizza.

Sci-athon is a collaborative event for graduate students and postdoctoral scholars designed to harness diverse scientific backgrounds toward solving global issues in chemistry. The last 2 years have yielded surprisingly different versions of this annual competition.

Cardiac mitochondrial function depends on BUD23 mediated ribosome programming.

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5'UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5'UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function.

Cells need to make proteins to survive, so they have protein-making machines called ribosomes. Ribosomes are themselves made out of proteins and RNA (a molecule similar to DNA), and they are assembled by other proteins that bring ribosomal components together and modify them until the ribosomes are functional.Mitochondria are compartments in the cell that are in charge of providing it with energy. To do this they require several proteins produced by the ribosomes. If not enough mitochondrial proteins are made, mitochondria cannot provide enough energy for the cell to survive.One of the proteins involved in modifying ribosomes so they are functional is called BUD23. People with certain diseases, such as Williams-Beuren syndrome, do not make enough BUD23; but it was unknown what specific effects resulted from a loss of BUD23.To answer this question, Baxter et al. first genetically removed BUD23 from human cells, and then checked what happened to protein production. They found that ribosomes in human cells with no BUD23 were different than in normal cells, and that cells without BUD23 produced different proteins, which did not always perform their roles correctly. Proteins in the mitochondria are one of the main groups affected by the absence of BUD23. To determine what effects these modified mitochondrial proteins would have in an animal, Baxter et al. genetically modified mice so that they no longer produced BUD23. These mice developed heart problems caused by their mitochondria not working correctly and being unable to provide the energy the heart cells needed, eventually leading to heart failure. Heart problems are common in people with Williams-Beuren syndrome.Many diseases arise when a person's mitochondria do not work properly, but it is often unclear why. These experiments suggest that low levels of BUD23 or faulty ribosomes may be causing mitochondria to work poorly in some of these diseases, which could lead to the development of new therapies.