Domain Composition Research Articles

Membrane organization by tetraspanins and galectins shapes lymphocyte function.

Immune receptors are not randomly distributed at the plasma membrane of lymphocytes but are segregated into specialized domains that function as platforms to initiate signalling, as exemplified by the B cell or T cell receptor complex and the immunological synapse. 'Membrane-organizing proteins' and, in particular, tetraspanins and galectins, are crucial for controlling the spatiotemporal organization of immune receptors and other signalling proteins. Deficiencies in specific tetraspanins and galectins result in impaired immune synapse formation, lymphocyte proliferation, antibody production and migration, which can lead to impaired immunity, tumour development and autoimmunity. In contrast to conventional ligand-receptor interactions, membrane organizers interact in cis (on the same cell) and modulate receptor clustering, receptor dynamics and intracellular signalling. New findings have uncovered their complex and dynamic nature, revealing shared binding partners and collaborative activity in determining the composition of membrane domains. Therefore, immune receptors should not be envisaged as independent entities and instead should be studied in the context of their spatial organization in the lymphocyte membrane. We advocate for a novel approach to study lymphocyte function by globally analysing the role of membrane organizers in the assembly of different membrane complexes and discuss opportunities to develop therapeutic approaches that act via the modulation of membrane organization.

Nanoscale X-ray Imaging of Composition and Ferroelastic Domains in Heterostructured Perovskite Nanowires: Implications for Optoelectronic Devices.

Metal halide perovskites (MHPs) have garnered significant interest as promising candidates for nanoscale optoelectronic applications due to their excellent optical properties. Axially heterostructured CsPbBr3-CsPb(Br(1-x)Clx)3 nanowires can be produced by localized anion exchange of pregrown CsPbBr3 nanowires. However, characterizing such heterostructures with sufficient strain and real space resolution is challenging. Here, we use nanofocused scanning X-ray diffraction (XRD) and X-ray fluorescence (XRF) with a 60 nm beam to investigate a heterostructured MHP nanowire as well as a reference CsPbBr3 nanowire. The nano-XRD approach gives spatially resolved maps of composition, lattice spacing, and lattice tilt. Both the reference and exchanged nanowire show signs of diverse types of ferroelastic domains, as revealed by the tilt maps. The chlorinated segment shows an average Cl composition of x = 66 and x = 70% as measured by XRD and XRF, respectively. The XRD measurements give a much more consistent result than the XRF ones. These findings are consistent with photoluminescence measurements, showing x = 73%. The nominally unexchanged segment also has a small concentration of Cl, as observed with all three methods, which we attribute to diffusion after processing. These results highlight the need to prevent such unwanted processes in order to fabricate optoelectronic devices based on MHP heterostructures.

AdVance™ male sling for stress urinary incontinence: Long-term follow-up and patient satisfaction.

To evaluate long-term effects, complications and satisfaction among patients treated with AdVance™ and AdVance™ XP slings (AS) at a Norwegian specialist care hospital. Patients who had an AS implanted due to stress urinary incontinence (SUI) 2009-2016 were identified retrospectively. Demographic and perioperative data were extracted from electronic patient files. We did a patient-reported outcome measure (PROM) survey with the Expanded Prostate Cancer Index Composite (EPIC-26) urinary domain and a Satisfaction Questionnaire (SQ) 2018-2020. Cure was defined as use of ≤1 pad/day. The AS was implanted in 165 patients, mainly due to mild to moderate SUI (median leakage 112 g, range 13-589 g/24 h). Preoperative urodynamics showed mild detrusor overactivity (DO) in 11 patients. At 6-week follow-up, 148 patients (90%) were cured. The most common complication was urinary retention (N = 38), transient in 32 patients (range 1-42 days). Two patients were later operated with division of the sling due to persistent retention. During clinical follow-up of up to 12 years, 27 patients were reoperated due to persistent/recurrent incontinence. The PROM survey was sent to 125 patients and 115 (92%) replied at median 73 (20-134) months postoperatively. Ninety-one (79%) used ≤1 pads/day, 97 (85%) were satisfied, one patient-reported pain. Regression analyses showed that failure (>1 pad/day) was significantly associated with a higher amount of leakage preoperatively and at the 6-week follow-up. Total cure rate in the complete cohort was 64% at median 73 (20-134) months follow-up. The AS shows good and persistent long-term results in patients with mild to moderate SUI. The only identified risk factor for long-term failure was higher amount of leakage preoperatively. The incidence of high body mass index (BMI), DO and previous radiotherapy was low and not significantly associated with failure but is still considered risk factors.

Genome-wide identification, phylogenetic relationships and expression patterns of the NOD-like receptor (NLR) gene family in flounder (Paralichthys olivaceus)

NOD-like receptors (NLRs) are one of the pattern recognition receptors which have been widely known for identifying pathogens and regulating innate immunity in mammals, but the functions of the NLR gene family in teleost fish remain poorly understood. In this study, we conducted a comprehensive identification and analysis of the flounder (Paralichthys olivaceus) NLR gene family, including bioinformatics information, evolutionary relationships, gene structures, conserved motifs, domain composition, expression patterns and protein-protein interaction (PPI). We identified 22 NLRs in flounder (flNLRs) which were clustered into three subfamilies according to their domain organizations and phylogenetic features, i.e., NLR-A (6 members) resembling mammalian NODs, NLR-B (1 member) resembling mammalian NLRPs, and NLR-C (15 members) unique to teleost fish. All flNLRs shared a conserved NACHT domain including an N-terminal nucleotide-binding domain, a middle helical domain 1, and a winged helix domain. Gene structure analysis displayed that flNLRs were significantly different, with exon numbers from 1 to 52. Conserved domain analysis showed that the N-terminus of flNLRs possessed different characteristics of the domains including CARD domain, PYRIN domain, RING domain, and fish-specific FISNA domain, and the C-terminus of seven NLR-C members contained an extra B30.2 domain, named NLRC-B30.2 group. Notably, flNLRs were expressed in all nine tested tissues, showing higher expressions in the systemic and mucosal immune tissues (e.g., kidney, spleen, hindgut, gills, skin, liver) in healthy flounder, and significant responses to intraperitoneal injection and immersion immunization of inactivated Vibrio anguillarum in mucosal tissues, especially the NLR-C members. In addition, PPI analysis demonstrated that some flNLRs of NLR-A and NLR-C shared the same interacting proteins such as RIPK2, TRAF6, MAVS, CASP, ASC, and ATG5, suggesting they might play crucial roles in host defense, antiviral innate immunity, inflammation, apoptosis and autophagy. This study for the first time characterized the NLR gene family of flounder at the genome-wide level, and the results provided a better understanding of the evolution of the NLR gene family and their immune functions in innate immunity in fish.

Polymetamorphism during the Grenvillian Orogeny in SE Ontario: Results from trace element mapping, in situ geochronology, and diffusion geospeedometry

AbstractThe Flinton Group is a metasedimentary succession of the Grenville Province in SE Ontario, potentially allowing insight into the tectono‐thermal evolution of continental crust during the Mesoproterozoic. At its Green Bay locality, Flinton Group metapelites of the staurolite zone contain abundant, post‐kinematic garnet porphyroblasts. Whereas the larger garnet crystals are typically impinged, smaller crystals are isolated from each other, occasionally exhibiting elongated shapes with apparently trigonal morphology. Central sections of the garnet population of a representative sample reveal that garnet is composed of different compositional and microstructural domains. In the largest crystals of the population, garnet contains rectangular to rhombic domains, marked by sharp increases in the concentrations of Nb, V, Ti, and Cr. These domains are associated with irregularly shaped patches, characterized by spatially heterogenous enrichments of Ca and LREE, and depletions in the contents of P, Y, MREE, and HREE, accompanied by increased densities of comparatively coarse‐grained quartz inclusions hosting apatite. Microstructural relationships indicate that these domains correspond to portions of garnet that pseudomorphed biotite, with the enrichments of Nb, V, Ti, and Cr outlining the original biotite shapes. The compositional patterns formed by Ca, P, Y, and REE indicate that apatite participated in the grain‐fluid interactions that operated during the metasomatic replacement of biotite by garnet. The statistical analyses of the garnet number and size distributions confirm that garnet initially nucleated on biotite, controlled by the kinetics of attachment and detachment processes at the garnet/biotite interface, resulting in the typical impingement habit. In situ Lu–Hf garnet geochronology applied to garnet that did not pseudomorph biotite, and hence is enriched in HREE, points to a first metamorphic event at c. 1080 31 Ma. Subsequent pseudomorphism of staurolite by white mica in a Al2O3‐ and FeO‐mobile system resulted in the concomitant crystallization of a new garnet generation, forming overgrowths on the first garnet generation and nuclei in the fine‐grained matrix. Garnet that nucleated during this event grew to isolated and elongated crystals with apparently trigonal morphology, aligned in a direction c. perpendicular to the rock matrix foliation. The open‐system behaviour during this event limits the use of whole‐rock‐based geochronological and thermobarometrical applications. However, previously published in situ U–Pb ages of monazite included in the rims of the garnet crystals and in the rock matrix indicate that this event took place at c. 976 4 Ma, likely associated with a period of increased hydrothermal activity late in the metamorphic history of the Grenvillian Orogeny. Diffusion geospeedometry calculations indicate that garnet growth during this hydrothermal event lasted for less than 6 Myr.

Formation of low-pressure reaction textures during near-isothermal exhumation of hot orogenic crust (Bohemian Massif, Austria).

Two types of aluminous paragneiss from the Loosdorf complex (Bohemian Massif, NE Austria) contain coarse-grained granulite assemblages and retrograde reaction textures that are investigated to constrain the post-peak history of the Gföhl unit in the southern Bohemian Massif. Both types have a peak assemblage garnet-biotite-sillimanite-plagioclase-K-feldspar-quartz-granitic melt ±kyanite ±ilmenite ±rutile, recording peak metamorphic conditions of 0.9-1.1 GPa and 780-820°Cestimated by isochemical phase equilibrium modelling. The first sample type (Ysper paragneiss) developed (i) cordierite coronae around garnet and (ii) cordierite-spinel and cordierite-quartz reaction textures at former garnet-sillimanite interfaces. Calculated chemical potential relationships indicate that the textures formed in the course of a post-peak near-isothermal decompression path reaching 0.4 GPa. Texture formation follows a two-step process. Initially, cordierite coronae grow between garnet and sillimanite. As these coronae thicken, they facilitate the development of local compositional domains, leading to the formation of cordierite-spinel and cordierite-quartz symplectites. The second sample type (Pielach paragneiss) exhibits only discontinuous cordierite coronae around garnet porphyroblasts but lacks symplectites. The formation of cordierite there also indicates near-isothermal decompression to 0.4-0.5 GPa and 750-800°C. This relatively hot decompression path is explained by the contemporaneous exhumation of a large HP-UHT granulite body now underlying the Loosdorf complex. The timing of regional metamorphism in the granulites and the southern Bohemian Massif in general is well constrained and has its peak at 340Ma. Monazite from Loosdorf paragneiss samples yield a slightly younger age of 335Ma. Although the ages overlap within error, they are interpreted to reflect near-isothermal decompression and exhumation resulting in the formation of the observed reaction textures.

Digital modeling-assisted mesoscale visualization lights up materials science from liquid- to solid-state batteries

A typical battery electrode is composed of polydisperse particles and porous composite binder domains. The arrangement of these constituent phases into complex mesoscopic structures plays a significant impact on electrochemical reaction and mechanical response, ultimately limiting macroscale battery performance. Limited by the spatial and temporal resolution of current characterization techniques, bridging digital modeling-assisted electrochemical simulation techniques can fully reveal the complicated mesoscale mechanisms in electrodes. The exploitation of digital twin-driven electrode models, visualization of physical and electrochemical behavior has become a prospect with the development of computing technology. This review summarizes the previous and current research focused on the digital model-derived to investigate the performance and the design of electrodes at mesoscale. The typical cases of electrochemical visualization in liquid and solid-state battery electrodes driven by digital modeling are discussed, including statistical characteristics of particles, heterogeneous reactions, and structure design of electrodes, which provide valuable insights into the complicated reaction mechanisms of batteries.

Identification of ARF transcription factor gene family and its defense responses to bacterial infection and salicylic acid treatment in sugarcane.

Auxin response factor (ARF) is a critical regulator in the auxin signaling pathway, involved in a variety of plant biological processes. Here, gene members of 24 SpapARFs and 39 SpnpARFs were identified in two genomes of Saccharum spontaneum clones AP85-441 and Np-X, respectively. Phylogenetic analysis showed that all ARF genes were clustered into four clades, which is identical to those ARF genes in maize (Zea mays) and sorghum (Sorghum bicolor). The gene structure and domain composition of this ARF family are conserved to a large degree across plant species. The SpapARF and SpnpARF genes were unevenly distributed on chromosomes 1-8 and 1-10 in the two genomes of AP85-441 and Np-X, respectively. Segmental duplication events may also contribute to this gene family expansion in S. spontaneum. The post-transcriptional regulation of ARF genes likely involves sugarcane against various stressors through a miRNA-medicated pathway. Expression levels of six representative ShARF genes were analyzed by qRT-PCR assays on two sugarcane cultivars [LCP85-384 (resistant to leaf scald) and ROC20 (susceptible to leaf scald)] triggered by Acidovorax avenae subsp. avenae (Aaa) and Xanthomonas albilineans (Xa) infections and salicylic acid (SA) treatment. ShARF04 functioned as a positive regulator under Xa and Aaa stress, whereas it was a negative regulator under SA treatment. ShARF07/17 genes played positive roles against both pathogenic bacteria and SA stresses. Additionally, ShARF22 was negatively modulated by Xa and Aaa stimuli in both cultivars, particularly LCP85-384. These findings imply that sugarcane ARFs exhibit functional redundancy and divergence against stressful conditions. This work lays the foundation for further research on ARF gene functions in sugarcane against diverse environmental stressors.

Go.Data as a digital tool for case investigation and contact tracing in the context of COVID-19: a mixed-methods study

BackgroundA manual approach to case investigation and contact tracing can introduce delays in response and challenges for field teams. Go.Data, an outbreak response tool developed by the World Health Organization (WHO) in collaboration with the Global Outbreak Alert and Response Network, streamlines data collection and analysis during outbreaks. This study aimed to characterize Go.Data use during COVID-19, elicit shared benefits and challenges, and highlight key opportunities for enhancement.MethodsThis study utilized mixed methods through qualitative interviews and a quantitative survey with Go.Data implementors on their experiences during COVID-19. Survey data was analyzed for basic univariate statistics. Interview data were coded using deductive and inductive reasoning and thematic analysis of categories. Overarching themes were triangulated with survey data to clarify key findings.ResultsFrom April to June 2022, the research team conducted 33 interviews and collected 41 survey responses. Participants were distributed across all six WHO regions and 28 countries. While most implementations represented government actors at national or subnational levels, additional inputs were collected from United Nations agencies and universities. Results highlighted WHO endorsement, accessibility, adaptability, and flexible support modalities as main enabling factors. Formalization and standardization of data systems and people processes to prepare for future outbreaks were a welcomed byproduct of implementation, as 76% used paper-based reporting prior and benefited from increased coordination around a shared platform. Several challenges surfaced, including shortage of the appropriate personnel and skill-mix within teams to ensure smooth implementation. Among opportunities for enhancements were improved product documentation and features to improve usability with large data volumes.ConclusionsThis study was the first to provide a comprehensive picture of Go.Data implementations during COVID-19 and what joint lessons could be learned. It ultimately demonstrated that Go.Data was a useful complement to responses across diverse contexts, and helped set a reproducible foundation for future outbreaks. Concerted preparedness efforts across the domains of workforce composition, data architecture and political sensitization should be prioritized as key ingredients for future Go.Data implementations. While major developments in Go.Data functionality have addressed some key gaps highlighted during the pandemic, continued dialogue between WHO and implementors, including cross-country experience sharing, is needed ensure the tool is reactive to evolving user needs.

Co-Expression of an IL-15 Superagonist Facilitates Self-Enrichment of GD2-Targeted CAR-NK Cells and Mediates Potent Cell Killing in the Absence of IL-2.

In contrast to T lymphocytes, natural killer (NK) cells do not require prior sensitization but are rapidly activated upon encountering virally infected or neoplastic cells. In addition, NK cells can be safely applied in an allogeneic setting, making them important effector cells for the development of off-the-shelf therapeutics for adoptive cancer immunotherapy. To further enhance their therapeutic potential, here, we engineered continuously expanding NK-92 cells as a clinically relevant model to express a humanized second-generation chimeric antigen receptor (CAR) with a composite CD28-CD3ζ signaling domain (hu14.18.28.z) that targets the disialoganglioside GD2, which is expressed at high levels by neuroblastoma cells and other tumors of neuroectodermal origin. In a separate approach, we fused an IL-15 superagonist (RD-IL15) to the GD2-CAR via a P2A processing site. Lentivirally transduced NK-92/hu14.18.28.z and NK-92/hu14.18.28.z_RD-IL15 cells both displayed high and stable CAR surface expression and specific cytotoxicity toward GD2-positive tumor cells. GD2-CAR NK cells carrying the RD-IL15 construct in addition expressed the IL-15 superagonist, resulting in self-enrichment and targeted cell killing in the absence of exogenous IL-2. Furthermore, co-culture with RD-IL15-secreting GD2-CAR NK cells markedly enhanced proliferation and cytotoxicity of bystander immune cells in a paracrine manner. Our results demonstrate that GD2-CAR NK cells co-expressing the IL-15 superagonist mediate potent direct and indirect antitumor effects, suggesting this strategy as a promising approach for the further development of functionally enhanced cellular therapeutics.

Genome-wide identification and bioinformatics analysis of the WD40 transcription factor family and candidate gene screening for anthocyanin biosynthesis in Rhododendron simsii

WD40 transcription factors (TFs) constitute a large gene family in eukaryotes, playing diverse roles in cellular processes. However, their functions in the major ornamental plant, Rhododendron simsii, remain poorly understood. In this study, we identified 258 WD40 proteins in the R. simsii genome, which exhibited an uneven distribution across chromosomes. Based on domain compositions and phylogenetic analysis, we classified these 258 RsWD40 proteins into 42 subfamilies and 47 clusters. Comparative genomic analysis suggested that the expansion of the WD40 gene family predates the divergence of green algae and higher plants, indicating an ancient origin. Furthermore, by analyzing the duplication patterns of RsWD40 genes, we found that transposed duplication played a major role in their expansion. Notably, the majority of RsWD40 gene duplication pairs underwent purifying selection during evolution. Synteny analysis identified significant orthologous gene pairs between R. simsii and Arabidopsis thaliana, Oryza sativa, Vitis vinifera, and Malus domestica. We also investigated potential candidate genes involved in anthocyanin biosynthesis during different flower development stages in R. simsii using RNA-seq data. Specifically, we identified 10 candidate genes during the bud stage and 7 candidate genes during the full bloom stage. GO enrichment analysis of these candidate genes revealed the potential involvement of the ubiquitination process in anthocyanin biosynthesis. Overall, our findings provide a valuable foundation for further investigation and functional analysis of WD40 genes, as well as research on the molecular mechanisms underlying anthocyanin biosynthesis in Rhododendron species.

Crystal plasticity and fluid availability govern the ability of titanite to record the age of deformation

Here, we study the relationships of titanite-hosting microdomains, intragrain chemical variations, microstructure and fluids with the aim of deciphering the reliability of titanite U–Pb dating to constrain the age of deformation in mylonitic rocks. We investigate these relationships in a post-Variscan amphibolite-facies shear zone developed in the mid-low continental crust (Ivrea-Verbano Zone, Southern Alps, Italy). Quantitative orientation analyses along with textural imaging of titanite are combined with trace-element analyses and U–Pb age dating. Titanite is studied in mm- to cm-scale layered rocks showing compositional variation consisting of alternating ‘amphibole-rich’ (i.e., amphibolites) and ‘clinopyroxene/plagioclase-rich’ domains (i.e., calc-silicates). Titanite from amphibole-rich domains shows predominance of crystal–plastic deformation features, as abrupt or progressive core-to-rim structures characterized by increasing lattice distortion and local dislocation density, associated with the development of abundant subgrains and rare newly nucleated grains. We suggest that these microstructures form while interacting with small amounts of fluids circulating along the grain boundaries. Consequently, locally the chemistry of titanite is changing. In the clinopyroxene/plagioclase-rich domains, titanite is mostly undeformed and rarely shows bending localized in discontinuous narrow rims/tips. In these domains, fluid-mediated replacement reactions are either rare or absent, as also indicated by weak chemical variations across and among grains. These observations suggest different reactivities with respect to the same P-T-fluid conditions of the two compositional domains, which coexist within the same sample at the thin section scale. U–Pb data show correlations with chemical and microstructural domains that differ as function of the composition of the microdomain. This correlation is more apparent within amphibole-rich domains where microstructures characterized by high lattice distortion/dislocations and/or subgrains show significant variations of REE, Zr, Y, Nb, U with respect to the low deformed portion of grains. These titanite domains define an isotopic population providing the youngest (Jurassic) lower intercept age. A less clear correlation between titanite chemistry and microstructures is observed in clinopyroxene/plagioclase-rich domains. Here, the rare titanites showing lattice distortion and minor Sr depletion define a population providing a similar Jurassic lower intercept age. Therefore, our results demonstrate that microstructurally and chemical calibrated U–Pb dating of titanite provides realistic ages of shear zone activity, only in case of predominance of crystal-plastic processes and of local interaction of titanite with small amounts of fluids focused along grain boundaries. Finally, the different footprints recorded by titanite grains strongly depend on the composition of cm- or mm-scale interlayered domains in which titanite occurs.

Predictors of Cognitive Change in Parkinson Disease: A 2-year Follow-up Study.

Mild cognitive impairment is common in Parkinson disease (PD-MCI). However, instability in this clinical diagnosis and variability in rates of progression to dementia raises questions regarding its utility for longitudinal tracking and prediction of cognitive change in PD. We examined baseline neuropsychological test and cognitive diagnosis predictors of cognitive change in PD. Persons with PD, without dementia PD (N=138) underwent comprehensive neuropsychological assessment at baseline and were followed up to 2 years. Level II Movement Disorder Society criteria for PD-MCI and PD dementia (PDD) were applied annually. Composite global and domain cognitive z -scores were calculated based on a 10-test neuropsychological battery. Baseline diagnosis of PD-MCI was not associated with a change in global cognitive z -scores. Lower baseline attention and higher executive domain z -scores were associated with greater global cognitive z -score worsening regardless of cognitive diagnosis. Worse baseline domain z -scores in the attention and language domains were associated with progression to MCI or PDD, whereas higher baseline scores in all cognitive domains except executive function were associated with clinical and psychometric reversion to "normal" cognition. Lower scores on cognitive tests of attention were predictive of worse global cognition over 2 years of follow-up in PD, and lower baseline attention and language scores were associated with progression to MCI or PDD. However, PD-MCI diagnosis per se was not predictive of cognitive decline over 2 years. The association between higher executive domain z -scores and greater global cognitive worsening is probably a spurious result.

Homogenization of a semilinear elliptic problem in a thin composite domain with an imperfect interface

In this paper, we consider the asymptotic behavior of a semilinear elliptic problem in a thin two‐composite domain with an imperfect interface, where the flux is discontinuous. For this thin domain, both the height and the period are of order . We first use Minty–Browder theorem to prove the well‐posedness of the problem and then apply the periodic unfolding method to obtain the limit problems and some corrector results for three cases of a real parameter , and , respectively. To deal with the semilinear terms, the extension operator and the averaged function are used.

Design and development of a new lead-free BiFeO3-BaTiO3 quenched ceramics for high piezoelectric strain performance

Designing a new high-performance lead-free ceramic has become a cutting-edge research topic due to growing concerns about the toxic nature of lead-based materials. In this work, a convenient strategy of compositional design and domain engineering is applied to the lead-fee BiFeO3-BaTiO3 ceramics which provides a flexible polarization free-energy profile for domain switching. Here, simultaneously enhanced dynamic piezoelectric constant (d33* ≈ 772 pm/V) and a good thermal-stability (Δd33* ≈ 26% over the temperature of 20–180 °C) are achieved with a high Curie temperature (TC) of 432 °C. This high piezoelectric strain performance is collectively attributed to multiple effects such as thermal quenching, suppression of defect charges by donor doping, chemically induced local structure heterogeneity, and electric field-induced phase transition. Furthermore, the addition of BT content decreased octahedral tilting that reduce anisotropy for domain switching and increased in tetragonality (cT/aT) providing a wider polar length for B-site cation displacement, leading to high piezoelectric strain performance. Atomic-resolution transmission electron microscopy and piezoelectric force microscopy combined with X-ray diffraction results strongly support the origin of high piezoelectricity. The high and temperature-stable piezoelectric strain response of this work is superior to those of other lead-free ceramics. The synergistic approach of composition design and the concept present here for the origin of high strain response provides a paradigm for the development of new materials for high-temperature piezoelectric actuator applications.

Bridging adsorption behavior of confined CH[formula omitted]-CO[formula omitted] binary mixtures across scales

An accurate understanding of the competitive adsorption of CH4-CO2 binary mixtures in nano-confined systems is critical for engineering CO2 storage in shale gas reservoirs. Due to difficulties in making reliable experimental observations in nano-scale, atomistic simulations (ASs), such as the Grand Canonical Monte Carlo (GCMC) method, provide a viable approach to studying the adsorption behavior of confined fluids. ASs are, however, limited in the size of the compositional domain due to the high computational cost. This work proposes a framework that combines AS and the lattice Boltzmann (LB) method to bridge the physics of confined fluids across scales. The Peng–Robinson equation of state (PR-EoS) produces fugacity coefficients, which serve as input for conducting multi-component GCMC simulations. These GCMC simulations explore the competitive adsorption behavior of CH4-CO2 in nano-slits at various composition, pressure, and channel-width conditions. Both components generate adsorption layers with high densities near the walls with CO2 preferentially adsorbing compared to CH4 on the organic walls of carbon sheets. At the mesoscale, a pseudopotential model represents the intermolecular forces in multi-component, multiple-relaxation-time LB simulations. The LB simulations are in good agreement with the GCMC results, allowing us to obtain values for tunable LB parameters. We then extend the use of LB to simulate adsorption behavior in complex networks with nano-sized channels. The phase behavior and fluid properties in the complex geometries of nano-channels differ from nano-slits and bulk systems. The bridging of physics from GCMC (microscale) to LB (mesoscale) via the macroscale PR-EoS connects the adsorption behavior of binary systems across scales.

Data-driven large-scale genomic analysis reveals an intricate phylogenetic and functional landscape in J-domain proteins

The 70-kD heat shock protein (Hsp70) chaperone system is a central hub of the proteostasis network that helps maintain protein homeostasis in all organisms. The recruitment of Hsp70 to perform different and specific cellular functions is regulated by the J-domain protein (JDP) co-chaperone family carrying the small namesake J-domain, required to interact and drive the ATPase cycle of Hsp70s. Besides the J-domain, prokaryotic and eukaryotic JDPs display a staggering diversity in domain architecture, function, and cellular localization. Very little is known about the overall JDP family, despite their essential role in cellular proteostasis, development, and its link to a broad range of human diseases. In this work, we leverage the exponentially increasing number of JDP gene sequences identified across all kingdoms owing to the advancements in sequencing technology and provide a broad overview of the JDP repertoire. Using an automated classification scheme based on artificial neural networks (ANNs), we demonstrate that the sequences of J-domains carry sufficient discriminatory information to reliably recover the phylogeny, localization, and domain composition of the corresponding full-length JDP. By harnessing the interpretability of the ANNs, we find that many of the discriminatory sequence positions match residues that form the interaction interface between the J-domain and Hsp70. This reveals that key residues within the J-domains have coevolved with their obligatory Hsp70 partners to build chaperone circuits for specific functions in cells.

Impact of Alcohol Use, Traumatic Stress, and Cigarette Smoking on Cognitive Functioning in Veterans With Co-occurring Alcohol Use Disorder and Posttraumatic Stress Disorder.

Alcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD. U.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition. Smoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers. Overall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers.

Narrow escape in composite domains forming heterogeneous networks

Cellular networks are often composed of thin tubules connecting much larger node compartments. These structures serve for active or diffusion transport of proteins. Examples are glial networks in the brain, the endoplasmic reticulum in cells or dendritic spines. In this latter case, a large ball forming the head is connected to the dendrite by a narrow passage. In all cases, how the transport of molecules, ions or proteins is regulated determines the time scale of chemical reactions or signal transduction. In the present study, based on modeling diffusion in three dimensions, we compute the mean time for a Brownian particle to reach a narrow target inside such a composite network made of tubules connected to spherical nodes. We derive asymptotic formulas by solving a mixed Neumann–Dirichlet boundary value problem with small Dirichlet part. We first consider the general case of a network domain organized in a 2-D lattice structure that consists of spherical ball compartments connected via narrow cylindrical passages. For a single target located on the boundary of one of the spherical domains, we derive a sparse linear system of equations for each Mean First Passage Time (MFPT) averaged over the different compartments. We then consider a composite domain consisting of a spherical head-like domain, with narrow absorbing targets on its boundary, that is connected to a large cylinder via a narrow cylindrical neck. For Brownian particles starting within the neck, we derive an asymptotic formula for the MFPT. When diffusing particles can be absorbed upon hitting additional absorbing boundaries of the large cylindrical compartment, we derive asymptotic formulas for the splitting probability and conditional MFPT to reach a target on the spherical head. We compare these formulas with numerical solutions of the mixed boundary value problem and with Brownian simulations, allowing to explore geometrical parameter ranges. To conclude, the present analysis reveals that the mean arrival time, driven by diffusion in heterogeneous networks, is controlled by the targets and tubules sizes, as well as the size of the nodal compartments.

Ruling by information, governing by records: the spoken and written grammar of power in post-communal Italy (c. 1350–1520)

ABSTRACTRecent research has widely emphasized the role of public written records and data-managing strategies in late-medieval governmental growth. The necessity to control information and to assure that a timely stream of news and communications circulated among the various components of a composite domain became central for princes and governments. Such a need was translated into new documentary techniques and archival organization by the endless work of many professionals at various territorial levels. However, the increasing recourse to recorded information was a multifaceted phenomenon. To better understand its complexity, the essay will investigate the intersection of spoken and written strategies of information-gathering and negotiation. Secondly, the paper will also take into account the ambivalent dynamics underlying the recording of the various means required not only to rule a composite territorial domain, but also to control its administrative, judicial and fiscal geography. Whereas the use of written records became the norm for the establishment of a new political order, that practice sometimes, and for different reasons, also contributed to preserving the memory of a different past. In order to adequately capitalize on late-medieval Italy’s complexity, the essay will examine different records and different contexts. The examples will be taken from a set of composite polities in post-communal northern and central Italy (ranging from Milan to Florence or Mantua) which shared some common features, but which were also different in size, strength, ideological models and material constitution. The considered timespan will be a long Quattrocento going from the mid-fourteenth to the early sixteenth century.