The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual ...building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here, we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy: the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from an amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme-packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. This study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales and exhibits properties and function that arise from the interaction between individual building blocks.
Merigo and colleagues argue that the meta-analyses and systematic reviews published in scientific journals in recent years is excessive, and that the primary goal is often more author-centric rather ...than to advance science. We agree that author benefits are not trivial, but some are foundational and important, especially for trainees. Trainees learn how to judge the quality of published evidence and create a comprehensive understanding in a selected topic, allowing for skill acquisition and a strong base for later work. This can stoke a future career and better insights by many, starting with the people who create these pieces.
As many physical properties of polymers scale with molecular weight, the ability to achieve polymers of nearly inaccessibly high molecular weight provides an opportunity to probe the upper size limit ...of macromolecular phenomena. Yet many of the most stimulating macromolecular designs remain out of reach of current ultrahigh molecular weight (UHMW) polymer synthetic approaches. Herein, we show that UHMW polymers of diverse composition can be achieved by irradiation of thiocarbonylthio photoiniferters with long-wave ultraviolet or visible light in concentrated organic solution. This facile photopolymerization strategy is general to acrylic-, acrylamido-, methacrylic-, and styrenic-based monomers, enabling the synthesis of well-defined macromolecules with molecular weights in excess of 106 g/mol. The high chain-end fidelity afforded by photoiniferter polymerization conditions facilitated the design of UHMW amphiphilic block copolymers, which were found to self-assemble into micellar morphologies up to 200 nm in diameter.
Insult-provoked transformation of neuronal networks into epileptic ones involves multiple mechanisms. Intervention studies have identified both dysregulated inflammatory pathways and NRSF-mediated ...repression of crucial neuronal genes as contributors to epileptogenesis. However, it remains unclear how epilepsy-provoking insults (e.g., prolonged seizures) induce both inflammation and NRSF and whether common mechanisms exist. We examined miR-124 as a candidate dual regulator of NRSF and inflammatory pathways. Status epilepticus (SE) led to reduced miR-124 expression via SIRT1—and, in turn, miR-124 repression—via C/EBPα upregulated NRSF. We tested whether augmenting miR-124 after SE would abort epileptogenesis by preventing inflammation and NRSF upregulation. SE-sustaining animals developed epilepsy, but supplementing miR-124 did not modify epileptogenesis. Examining this result further, we found that synthetic miR-124 not only effectively blocked NRSF upregulation and rescued NRSF target genes, but also augmented microglia activation and inflammatory cytokines. Thus, miR-124 attenuates epileptogenesis via NRSF while promoting epilepsy via inflammation.
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•Epilepsy-provoking insults (SE) repress miR-124 via SIRT1 activation•miR-124 repression controls both inflammation and NRSF•miR-124 replenishment does not prevent epileptogenesis•miR-124 activates microglia in control and SE hippocampus
Brennan et al. find that miR-124 is involved in insult-induced epilepsy. They find that activation of SIRT1 represses miR124. This repression affects miR-124 targeting of NRSF; however, it may also act to reduce inflammation that contributes to epilepsy development. Thus, miR-124 has opposing roles in the development of epilepsy.
Morphology plays an essential role in chemistry through the segregation of atoms and/or molecules into different phases, delineated by interfaces. This is a general process in materials synthesis and ...exploited in many fields including colloid chemistry, heterogeneous catalysis, and functional molecular systems. To rationally design complex materials, we must understand and control morphology evolution. Toward this goal, we utilize cryogenic transmission electron microscopy (cryoTEM), which can track the structural evolution of materials in solution with nanometer spatial resolution and a temporal resolution of <1 s. In this Account, we review examples of our own research where direct observations by cryoTEM have been essential to understanding morphology evolution in macromolecular self-assembly, inorganic nucleation and growth, and the cooperative evolution of hybrid materials. These three different research areas are at the heart of our approach to materials chemistry where we take inspiration from the myriad examples of complex materials in Nature. Biological materials are formed using a limited number of chemical components and under ambient conditions, and their formation pathways were refined during biological evolution by enormous trial and error approaches to self-organization and biomineralization. By combining the information on what is possible in nature and by focusing on a limited number of chemical components, we aim to provide an essential insight into the role of structure evolution in materials synthesis. Bone, for example, is a hierarchical and hybrid material which is lightweight, yet strong and hard. It is formed by the hierarchical self-assembly of collagen into a macromolecular template with nano- and microscale structure. This template then directs the nucleation and growth of oriented, nanoscale calcium phosphate crystals to form the composite material. Fundamental insight into controlling these structuring processes will eventually allow us to design such complex materials with predetermined and potentially unique properties.
Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with ...the adjacent radial glial endfeet and influence cortical development. We took advantage of
Foxc1 mutant mice with defects in forebrain meningeal formation.
Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition,
Rdh10- and
Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the
Foxc1 mutants, and
Rdh10 mutants had a cortical phenotype similar to the
Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in
Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.
There is no safe level of exposure to inorganic arsenic or uranium, yet recent studies identified sociodemographic and regional inequalities in concentrations of these frequently detected ...contaminants in public water systems across the US. We analyze the county-level association between racial/ethnic composition and public water arsenic and uranium concentrations from 2000-2011 using geospatial models. We find that higher proportions of Hispanic/Latino and American Indian/Alaskan Native residents are associated with significantly higher arsenic and uranium concentrations. These associations differ in magnitude and direction across regions; higher proportions of non-Hispanic Black residents are associated with higher arsenic and uranium in regions where concentrations of these contaminants are high. The findings from this nationwide geospatial analysis identifying racial/ethnic inequalities in arsenic and uranium concentrations in public drinking water across the US can advance environmental justice initiatives by informing regulatory action and financial and technical support to protect communities of color.
Vaccine hesitancy limits population protection from SARS-CoV (coronavirus disease COVID-19). Vaccine hesitancy among healthcare workers (HCW) could put patients and coworkers at risk.
We surveyed 475 ...emergency department and emergency medical service workers from January to February 2021 to determine vaccine intent/uptake, perceived COVID-19 vulnerability, and factors associated with vaccine intent/uptake.
Although 79% of HCWs received or had plans to receive the COVID-19 vaccine, 21% had no intent/were unvaccinated; intent/uptake was lower among females (odds ratio OR = 0.34) and those with a history of COVID-19 infection (OR = 0.55), and higher among those with advanced degrees (OR = 3.53) and high perceived COVID-19 vulnerability (OR = 1.99).
This study provides a timely assessment of vaccination status among frontline HCWs and highlights subgroups who may be at high risk of exposure and transmission.
This study aimed to test the effect of a 30-minute nap versus a 2-hour nap opportunity taken during a simulated night shift on performance, fatigue, sleepiness, mood, and sleep at the end of shift ...and during post-night shift recovery.
We conducted a randomized crossover trial of three nap conditions (30-minute, 2-hour, and no-nap) during 12-hour simulated night shifts. We tested for differences in performance, fatigue, sleepiness, mood, and sleep during in-lab and at-home recovery. Performance was measured with the Brief Psychomotor Vigilance Test (PVT-B). Subjective ratings were assessed with single-item surveys.
Twenty-eight individuals consented to participate mean age 24.4 (standard deviation 7.2) years; 53.6% female; 85.7% Emergency Medical Services clinicians. PVT-B false starts at the end of the 12-hour night shift (at 07:00 hours) and at the start of in-lab recovery (08:00 hours) were lower following the 2-hour nap versus other conditions (P<0.05). PVT-B response time at +0 minutes post-recovery nap was poorer compared to pre-recovery nap for the no-nap condition (P=0.003), yet not detected for other nap conditions (P>0.05). Sleepiness, fatigue, and some mood states were lower at most hourly assessments during the in-lab recovery period following the 2-hour nap condition compared to the other conditions. Sleep during recovery did not differ by duration of night shift nap.
A 2-hour nap opportunity versus a 30-minute or no-nap opportunity is beneficial for performance, alertness, and mood post-night shift. No differences were detected in sleep during recovery.
Abstract
Risks associated with fatigue that accumulates during work shifts have historically been managed through working time arrangements that specify fixed maximum durations of work shifts and ...minimum durations of time off. By themselves, such arrangements are not sufficient to curb risks to performance, safety, and health caused by misalignment between work schedules and the biological regulation of waking alertness and sleep. Science-based approaches for determining shift duration and mitigating associated risks, while addressing operational needs, require: (1) a recognition of the factors contributing to fatigue and fatigue-related risks; (2) an understanding of evidence-based countermeasures that may reduce fatigue and/or fatigue-related risks; and (3) an informed approach to selecting workplace-specific strategies for managing work hours. We propose a series of guiding principles to assist stakeholders with designing a shift duration decision-making process that effectively balances the need to meet operational demands with the need to manage fatigue-related risks.
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