Dendrite initiation and propagation in lithium metal solid-state batteries.

All-solid-state batteries with a Li anode and ceramic electrolyte have the potential to deliver a step change in performance compared with today's Li-ion batteries1,2. However, Li dendrites (filaments) form on charging at practical rates and penetrate the ceramic electrolyte, leading to short circuit and cell failure3,4. Previous models of dendrite penetration have generally focused on a single process for dendrite initiation and propagation, with Li driving the crack at its tip5-9. Here we show that initiation and propagation are separate processes. Initiation arises from Li deposition into subsurface pores, by means of microcracks that connect the pores to the surface. Once filled, further charging builds pressure in the pores owing to the slow extrusion of Li (viscoplastic flow) back to the surface, leading to cracking. By contrast, dendrite propagation occurs by wedge opening, with Li driving the dry crack from the rear, not the tip. Whereas initiation is determined by the local (microscopic) fracture strength at the grain boundaries, the pore size, pore population density and current density, propagation depends on the (macroscopic) fracture toughness of the ceramic, the length of the Li dendrite (filament) that partially occupies the dry crack, current density, stack pressure and the charge capacity accessed during each cycle. Lower stack pressures suppress propagation, markedly extending the number of cycles before short circuit in cells in which dendrites have initiated.

Ant-icipating Change: An Epigenetic Switch in Reprogramming the Social Lives of Ants.

Glastad et al. (2019) describe a role for the neuronal CoREST corepressor and changes in juvenile hormone (JH) and ecdysone signaling during the reprogramming of social behavioral phenotypes in ants that are reflective of a natural mechanism differentiating "Major" and "Minor" worker ants.

Clinical Guidelines for Working with Clients Involved in Kink.

People involved in kink (BDSM or fetish) subcultures often encounter stigma and bias in healthcare settings or when seeking psychotherapy. Such individuals typically encounter well-meaning clinicians who are not prepared to provide culturally competent care or who have not recognized their own biases. Over a two-year period, a team of 20 experienced clinicians and researchers created clinical practice guidelines for working with people involved with kink, incorporating an extensive literature review and documentation of clinical expertise. This article summarizes the guidelines and discusses relevant issues facing clinicians and their clients, as well as implications for clinical practice, research and training.

Histone H3 lysine 4 methylation signature associated with human undernutrition.

Chronically undernourished children become stunted during their first 2 years and thereafter bear burdens of ill health for the rest of their lives. Contributors to stunting include poor nutrition and exposure to pathogens, and parental history may also play a role. However, the epigenetic impact of a poor environment on young children is largely unknown. Here we show the unfolding pattern of histone H3 lysine 4 trimethylation (H3K4me3) in children and mothers living in an urban slum in Dhaka, Bangladesh. A pattern of chromatin modification in blood cells of stunted children emerges over time and involves a global decrease in methylation at canonical locations near gene start sites and increased methylation at ectopic sites throughout the genome. This redistribution occurs at metabolic and immune genes and was specific for H3K4me3, as it was not observed for histone H3 lysine 27 acetylation in the same samples. Methylation changes in stunting globally resemble changes that occur in vitro in response to altered methylation capacity, suggesting that reduced levels of one-carbon nutrients in the diet play a key role in stunting in this population. A network of differentially expressed genes in stunted children reveals effects on chromatin modification machinery, including turnover of H3K4me3, as well as posttranscriptional gene regulation affecting immune response pathways and lipid metabolism. Consistent with these changes, reduced expression of the endocytic receptor gene LDL receptor 1 (LRP1) is a driver of stunting in a mouse model, suggesting a target for intervention.

3D-printed λ/4 phase plate for broadband microwave applications.

An efficient design for a quarter-wave (λ/4) retardation plate (QWP) operating at microwave frequencies has been designed and manufactured using dual head fused deposition modelling (FDM) 3D printing. Exploiting a bespoke composite material feedstock filament with high dielectric permittivity ϵr = 10.8, the resulting 3D-printed QWP comprising alternative layers of high and low permittivity had a high artificial double refraction of Δϵ = 2.9. The QWP provided broadband conversion of linear to circular polarization and phase modulation of an incident plane electromagnetic wave at 12-18 GHz, and demonstrated the potential for optical devices via additive manufacture for use in the microwave frequency range.

Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation.

The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an important chromatin modifying complex that can both acetylate and deubiquitinate histones. Sgf29 is a novel component of the SAGA complex. Here, we report the crystal structures of the tandem Tudor domains of Saccharomyces cerevisiae and human Sgf29 and their complexes with H3K4me2 and H3K4me3 peptides, respectively, and show that Sgf29 selectively binds H3K4me2/3 marks. Our crystal structures reveal that Sgf29 harbours unique tandem Tudor domains in its C-terminus. The tandem Tudor domains in Sgf29 tightly pack against each other face-to-face with each Tudor domain harbouring a negatively charged pocket accommodating the first residue alanine and methylated K4 residue of histone H3, respectively. The H3A1 and K4me3 binding pockets and the limited binding cleft length between these two binding pockets are the structural determinants in conferring the ability of Sgf29 to selectively recognize H3K4me2/3. Our in vitro and in vivo functional assays show that Sgf29 recognizes methylated H3K4 to recruit the SAGA complex to its targets sites and mediates histone H3 acetylation, underscoring the importance of Sgf29 in gene regulation.

Spatial transformations: from fundamentals to applications.

This paper forms the introduction to this themed issue of Philosophical Transactions of the Royal Society A on 'Spatial transformations', arising from the Royal Society Scientific Discussion Meeting held in January 2015. The paper begins with a review of the concepts and history of spatial transformations, followed by a discussion of the contributions from the papers in this themed issue. A summary of the advantages and current limitations of spatial transformations concludes the paper, with the key challenges identified at the Scientific Discussion Meeting also given.

Reelin is a target of polyglutamine expanded ataxin-7 in human spinocerebellar ataxia type 7 (SCA7) astrocytes.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant neurodegenerative disorder that results from polyglutamine expansion of the ataxin-7 (ATXN7) protein. Remarkably, although mutant ATXN7 is expressed throughout the body, pathology is restricted primarily to the cerebellum and retina. One major goal has been to identify factors that contribute to the tissue specificity of SCA7. Here we describe the development and use of a human astrocyte cell culture model to identify reelin, a factor intimately involved in the development and maintenance of Purkinje cells and the cerebellum as a whole, as an ATXN7 target gene. We found that polyglutamine expansion decreased ATXN7 occupancy, which correlated with increased levels of histone H2B monoubiquitination, at the reelin promoter. Treatment with trichostatin A, but not other histone deacetylase inhibitors, partially restored reelin transcription and promoted the accumulation of mutant ATXN7 into nuclear inclusions. Our findings suggest that reelin could be a previously unknown factor involved in the tissue specificity of SCA7 and that trichostatin A may ameliorate deleterious effects of the mutant ATXN7 protein by promoting its sequestration away from promoters into nuclear inclusions.

Direct inhibition of Gcn5 protein catalytic activity by polyglutamine-expanded ataxin-7.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by polyglutamine (polyQ) expansion within the N-terminal region of the ataxin-7 protein, a known subunit of the SAGA complex. Although the mechanisms of SCA7 pathogenesis remain poorly understood, previous studies have shown perturbations in SAGA histone acetyltransferase function and transcriptional alterations. We sought to determine whether and how polyQ-expanded ataxin-7 affects SAGA catalytic activity. Here, we determined that polyQ-expanded ataxin-7 directly bound the Gcn5 catalytic core of SAGA while in association with its regulatory proteins, Ada2 and Ada3. This caused a significant decrease in Gcn5 histone acetyltransferase activity in vitro and in vivo at two SAGA-regulated galactose genes, GAL1 and GAL7. However, Gcn5 occupancy at the GAL1 and GAL7 promoters was increased in these cells, revealing a dominant-negative phenotype of the polyQ-expanded ataxin-7-incorporated, catalytically inactive SAGA. These findings suggest a dominant mechanism of polyQ-mediated SAGA inhibition that potentially contributes to SCA7 disease pathogenesis.

Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat encoding a polyglutamine tract in ATXN7, a component of the SAGA histone acetyltransferase (HAT) complex. Previous studies provided conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here, we report that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing wild-type (wt) Atxn7, however, causes only mild ataxia and does not lead to the early lethality observed in SCA7 mice. Reduced Gcn5 expression strongly enhances retinopathy in SCA7 mice, but does not affect the known transcriptional targets of Atxn7, as expression of these genes is not further altered by Gcn5 depletion. These findings demonstrate that loss of Gcn5 functions can contribute to the time of onset and severity of SCA7 phenotypes, and suggest that non-transcriptional functions of SAGA may play a role in neurodegeneration in this disease.

Core-shell nanoparticles and enhanced polarization in polymer based nanocomposite dielectrics.

We present a detailed study of the evolution and nature of metallic core-oxide shell particles and the role of nanostructure in the physics of enhanced polarization in polymer-nanocomposite (PNC) based dielectrics. Nylon-6 based PNCs consisting of aluminium (core)-aluminium oxide (shell) nanoparticles were fabricated by a vacuum deposition technique. Their resulting high polarizability was closely related to the formation and chemistry of the core-shell structure that was revealed by transmission electron microscopy to comprise a highly-defective, strained and non-stoichiometric semi-crystalline/amorphous Al-oxide shell.

The role of DNA methylation and histone modifications in transcriptional regulation in humans.

Although the field of genetics has grown by leaps and bounds within the last decade due to the completion and availability of the human genome sequence, transcriptional regulation still cannot be explained solely by an individual's DNA sequence. Complex coordination and communication between a plethora of well-conserved chromatin modifying factors are essential for all organisms. Regulation of gene expression depends on histone post translational modifications (HPTMs), DNA methylation, histone variants, remodeling enzymes, and effector proteins that influence the structure and function of chromatin, which affects a broad spectrum of cellular processes such as DNA repair, DNA replication, growth, and proliferation. If mutated or deleted, many of these factors can result in human disease at the level of transcriptional regulation. The common goal of recent studies is to understand disease states at the stage of altered gene expression. Utilizing information gained from new high-throughput techniques and analyses will aid biomedical research in the development of treatments that work at one of the most basic levels of gene expression, chromatin. This chapter will discuss the effects of and mechanism by which histone modifications and DNA methylation affect transcriptional regulation.

Elemental composition of human semen is associated with motility and genomic sperm defects among older men.

BACKGROUND: Older men tend to have poorer semen quality and are generally at higher risks for infertility and abnormal reproductive outcomes. METHODS: We employed proton-induced X-ray emission (PIXE, 3 MeV proton beam) to investigate the concentrations of zinc, copper, calcium, sulfur, chlorine, potassium, titanium, iron and nickel in washed sperm and seminal plasma from non-smoking groups of 10 older men (65-80 years old) and 10 younger men (22-28 years old) who were concurrently assayed for sperm function and genomicly defective sperm. RESULTS: The older group showed elevated zinc, copper and calcium in sperm and elevated sulfur in seminal plasma compared with the younger men. The older group also showed reduced motility as well as increased sperm DNA fragmentation, achondroplasia mutations, DNA strand breaks and chromosomal aberrations. Sperm calcium and copper were positively associated with sperm DNA fragmentation (P < 0.03). Seminal sulfur was positively associated with sperm DNA fragmentation and chromosomal aberrations (P < 0.04), and negatively associated with sperm motility (P < 0.05). Sperm calcium was negatively associated with sperm motility, independent of male age (P = 0.01). CONCLUSIONS: We identified major differences in elemental concentrations between sperm and seminal plasma and that higher sperm copper, sulfur and calcium are quantitatively associated with poorer semen quality and increased frequencies of genomic sperm defects.

Spray fabrication of additive-free electrodes for advanced Lithium-Ion storage technologies.

Polymer binders and carbon conductivity enhancers are inevitably required to make improvements in structural durability and electrochemical performance of lithium-ion battery (LIB) electrodes, although these additive constituents incur weight and volume penalties on the overall battery capacity. Here, additive-free electrode architectures were successfully fabricated over 20 × 20 cm2 electrode areas using a layer-by-layer spray coating approach, with the ultimate goal to boost gravimetric/volumetric electrode capacity and to reduce the total cost of LIB cells. Initially, the binder fraction of spray-coated Li4Ti5O12 (LTO) electrodes was reduced progressively, from 40 to 0 wt%. The electrochemical behavior of electrodes was then re-optimized as a proportion of conductivity enhancers within the binder-free electrode decreased to zero. Further, the otherwise identical spray coating process was applied to manufacture LiFePO4 (LFP) positive electrodes, leading to all-additive-free full-cell LIB configurations with attractive energy density of âˆ¼310 Wh/kg and power performance of âˆ¼1500 W/kg.

Globally elevated levels of histone H3 lysine 9 trimethylation in early infancy are associated with poor growth trajectory in Bangladeshi children.

BACKGROUND: Stunting is a global health problem affecting hundreds of millions of children worldwide and contributing to 45% of deaths in children under the age of five. Current therapeutic interventions have limited efficacy. Understanding the epigenetic changes underlying stunting will elucidate molecular mechanisms and likely lead to new therapies. RESULTS: We profiled the repressive mark histone H3 lysine 9 trimethylation (H3K9me3) genome-wide in peripheral blood mononuclear cells (PBMCs) from 18-week-old infants (n = 15) and mothers (n = 14) enrolled in the PROVIDE study established in an urban slum in Bangladesh. We associated H3K9me3 levels within individual loci as well as genome-wide with anthropometric measurements and other biomarkers of stunting and performed functional annotation of differentially affected regions. Despite the relatively small number of samples from this vulnerable population, we observed globally elevated H3K9me3 levels were associated with poor linear growth between birth and one year of age. A large proportion of the differentially methylated genes code for proteins targeting viral mRNA and highly significant regions were enriched in transposon elements with potential regulatory roles in immune system activation and cytokine production. Maternal data show a similar trend with child's anthropometry; however, these trends lack statistical significance to infer an intergenerational relationship. CONCLUSIONS: We speculate that high H3K9me3 levels may result in poor linear growth by repressing genes involved in immune system activation. Importantly, changes to H3K9me3 were detectable before the overt manifestation of stunting and therefore may be valuable as new biomarkers of stunting.

Transcriptional Profile of Exercise-Induced Protection Against Relapse to Cocaine Seeking in a Rat Model.

Background: Exercise has shown promise as a treatment for cocaine use disorder; however, the mechanism underlying its efficacy has remained elusive. Methods: We used a rat model of relapse (cue-induced reinstatement) and exercise (wheel running, 2 hours/day) coupled with RNA sequencing to establish transcriptional profiles associated with the protective effects of exercise (during early withdrawal [days 1-7] or throughout withdrawal [days 1-14]) versus noneffective exercise (during late withdrawal [days 8-14]) against cocaine-seeking and sedentary conditions. Results: As expected, cue-induced cocaine seeking was highest in the sedentary and late-withdrawal exercise groups; both groups also showed upregulation of a Grin1-associated transcript and enrichment of Drd1-Nmdar1 complex and glutamate receptor complex terms. Surprisingly, these glutamate markers were also enriched in the early- and throughout-withdrawal exercise groups, despite lower levels of cocaine seeking. However, a closer examination of the Grin1-associated transcript revealed a robust loss of transcripts spanning exons 9 and 10 in the sedentary condition relative to saline controls that was normalized by early- and throughout-withdrawal exercise, but not late-withdrawal exercise, indicating that these exercise conditions may normalize RNA mis-splicing induced by cocaine seeking. Our findings also revealed novel mechanisms by which exercise initiated during early withdrawal may modulate glutamatergic signaling in dorsomedial prefrontal cortex (e.g., via transcripts associated with non-NMDA glutamate receptors or those affecting signaling downstream of NMDA receptors), along with mechanisms outside of glutamatergic signaling such as circadian rhythm regulation and neuronal survival. Conclusions: These findings provide a rich resource for future studies aimed at manipulating these molecular networks to better understand how exercise decreases cocaine seeking.

Numerical Design of Microporous Carbon Binder Domains Phase in Composite Cathodes for Lithium-Ion Batteries.

Lithium-ion battery (LIB) performance can be significantly affected by the nature of the complex electrode microstructure. The carbon binder domain (CBD) present in almost all LIB electrodes is used to enhance mechanical stability and facilitate electronic conduction, and understanding the CBD phase microstructure and how it affects the complex coupled transport processes is crucial to LIB performance optimization. In this work, the influence of microporosity in the CBD phase has been studied in detail for the first time, enabling insight into the relationships between the CBD microstructure and the battery performance. To investigate the effect of the CBD pore size distributions, a random field method is used to generate in silico a multiple-phase electrode structure, including bimodal pore size distributions seen in practice and microporous CBD with a tunable pore size and variable transport properties. The distribution of macropores and the microporous CBD phase substantially affected simulated battery performance, where battery specific capacity improved as the microporosity of the CBD phase increased.

WD repeat-containing protein 5, a ubiquitously expressed histone methyltransferase adaptor protein, regulates smooth muscle cell-selective gene activation through interaction with pituitary homeobox 2.

WD repeat-containing protein 5 (WDR5) is a common component of mammalian mixed lineage leukemia methyltransferase family members and is important for histone H3 lysine 4 methylation (H3K4me), which has been implicated in control of activation of cell lineage genes during embryogenesis. However, WDR5 has not been considered to play a specific regulatory role in epigenetic programming of cell lineage because it is ubiquitously expressed. Previous work from our laboratory showed the appearance of histone H3K4me within smooth muscle cell (SMC)-marker gene promoters during the early stages of development of SMC from multipotential embryonic cells but did not elucidate the underlying mechanisms that mediate SMC-specific and locus-selective H3K4me. Results presented herein show that knockdown of WDR5 significantly decreased SMC-marker gene expression in cultured SMC differentiation systems and in Xenopus laevis embryos in vivo. In addition, we showed that WDR5 complexes within SMC progenitor cells contained H3K4 methyltransferase enzymatic activity and that knockdown of WDR5 selectively decreased H3K4me1 and H3K4me3 enrichment within SMC-marker gene promoter loci. Moreover, we present evidence that it is recruited to these gene promoter loci through interaction with a SMC-selective pituitary homeobox 2 (Pitx2). Taken together, studies provide evidence for a novel mechanism for epigenetic control of SMC-marker gene expression during development through interaction of WDR5, homeodomain proteins, and chromatin remodeling enzymes.

Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes.

Despite the availability of several large-scale proteomics studies aiming to identify protein interactions on a global scale, little is known about how proteins interact and are organized within macromolecular complexes. Here, we describe a technique that consists of a combination of biochemistry approaches, quantitative proteomics and computational methods using wild-type and deletion strains to investigate the organization of proteins within macromolecular protein complexes. We applied this technique to determine the organization of two well-studied complexes, Spt-Ada-Gcn5 histone acetyltransferase (SAGA) and ADA, for which no comprehensive high-resolution structures exist. This approach revealed that SAGA/ADA is composed of five distinct functional modules, which can persist separately. Furthermore, we identified a novel subunit of the ADA complex, termed Ahc2, and characterized Sgf29 as an ADA family protein present in all Gcn5 histone acetyltransferase complexes. Finally, we propose a model for the architecture of the SAGA and ADA complexes, which predicts novel functional associations within the SAGA complex and provides mechanistic insights into phenotypical observations in SAGA mutants.

Sequential Deposition of Integrated Cathode-Inorganic Separator-Anode Multilayers for High Performance Li-Ion Batteries.

A porous, spray-deposited Al2O3-based separator was developed to enable the direct deposition of an electrode/separator/electrode Li-ion battery full cell assembly in a single operation. The optimized sprayed separator consisted of 50 nm Al2O3 particles, 1 wt % poly(acrylic acid), and 5 wt % styrene-butadiene rubber, deposited from an 80:20 vol % suspension of water and isopropanol. Separators between 5 and 22 µm thick had consistent and similar porosity of ∼58%, excellent wettability, thermal stability to at least 180 °C, adequate electrochemical stability and high effective ionic conductivity of ∼1 mS cm-1 at room temperature in an EC/DMC electrolyte, roughly double that of a conventional polypropylene separator. A sequentially deposited three-layer LiFePO4/Al2O3/Li4Ti5O12 full cell, the first of its kind, showed similar rate performance to an identical cell with a conventional polypropylene separator, with a capacity of ∼50 mAh g-1 at 30 C. However, after cycling at 2 C for 400 cycles, Al2O3 separator full cells retained 96.3% capacity, significantly more than conventional full cells with a capacity of 79.2% remaining.