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We report device-level damping measurements using spin-torque driven ferromagnetic resonance on perpendicular magnetic random-access memory cells. It is shown that thermal agitation enhances the apparent damping for cells smaller than about 55 nm. The effect is fundamental and does not reflect a true damping increase. In addition to the thermal effect, it is still found that device-level damping is higher than film-level damping and increases with decreasing cell size. This is attributed to edge damage caused by device patterning. [ABSTRACT FROM AUTHOR]

The calculation of the demagnetization field is crucial in various disciplines, including magnetic resonance imaging and micromagnetics. A standard method involves discretizing the spatial domain into finite difference cells and using demagnetization tensors to compute the field. Different demagnetization tensors can result in contributions from adjacent cells that do not approach zero, nor do their differences, even as the cell size decreases. This work demonstrates that in three-dimensional space, a specific set of magnetization tensors produces the same total demagnetization field as the Cauchy principal value when the cell size approaches zero. Additionally, we provide a lower bound for the convergence speed, validated through numerical experiments. [ABSTRACT FROM AUTHOR]

We successfully synthesized tetragonal FeS with various Fe:S molar ratios using a hydrothermal method, and the EDS and XRF results confirmed that FeS exhibits superconductivity within the Fe and S element ratio range of 1.155–1.274, rather than a strict stoichiometric ratio. The reaction temperature can not only play a crucial role in determining the purity of the obtained FeS phase but also significantly alter its micromorphology. Significantly, by analyzing the relationship between the Fe:S actual molar ratio and Tc as well as the Fe:S actual molar ratio and unit cell volume, FeS exhibits dome-shaped superconductivity and shows a negative correlation with Tc and chemical pressure. Furthermore, considering the correlation between anion height (hanion) and Tc, Tc reaches the maximum value of 4.53 K for hanion ≈ 1.28 Å, a behavior distinct from that of observed in Fe-pnictide superconductors. In short, our experimental results provide a unique perspective to deepen our understanding of FeS superconductors. [ABSTRACT FROM AUTHOR]

In this study, phase transitions (structural and magnetic) and associated magnetocaloric properties of stoichiometric MnCoGe have been investigated as a function of annealing pressure. Metastable phases were generated by annealing at 800 ° C followed by rapid cooling under pressures up to 6.0 GPa. The x-ray diffraction results reveal that the crystal cell volume of the metastable phases continuously decreases with increasing thermal processing pressure, leading to a decrease in the structural transition temperature. The magnetic and structural transitions merge and form a first-order magnetostructural transition between the ferromagnetic orthorhombic and paramagnetic hexagonal phases over a broad temperature range (>80 K) spanning room temperature, yielding considerable magnetic entropy changes. These findings demonstrate the utility of thermal processing under high pressure, i.e., high-pressure annealing, to control the magnetostructural transitions and associated magnetocaloric properties of MnCoGe without altering its chemical composition. [ABSTRACT FROM AUTHOR]

Entry into the cell cycle in late G1 phase occurs only when sufficient growth has occurred. In budding yeast, a cyclin called Cln3 is thought to link cell-cycle entry to cell growth. Cln3 accumulates during growth in early G1 phase and eventually helps trigger expression of late G1 phase cyclins that drive cell-cycle entry. All current models for cell-cycle entry assume that expression of late G1 phase cyclins is initiated at the transcriptional level. Current models also assume that the sole function of Cln3 in cell-cycle entry is to promote transcription of late G1 phase cyclins, and that Cln3 works solely in G1 phase. Here, we show that cell cycle-dependent expression of the late G1 phase cyclin Cln2 does not require any functions of the CLN2 promoter. Moreover, Cln3 can influence accumulation of Cln2 protein via posttranscriptional mechanisms. Finally, we show that Cln3 has functions in mitosis that strongly influence cell size. Together, these discoveries reveal the existence of surprising new mechanisms that challenge current models for control of cell-cycle entry and cell size.

Structural studies using x-ray scattering methods for investigating molecules in solution are shifting focus toward describing the role and effects of the surrounding solvent. However, forward models based on molecular dynamics (MD) simulations to simulate structure factors and x-ray scattering from interatomic distributions such as radial distribution functions (RDFs) face limitations imposed by simulations, particularly at low values of the scattering vector q. In this work, we show how the value of the structure factor at q = 0 calculated from RDFs sampled from finite MD simulations is effectively dependent on the size of the simulation cell. To eliminate this error, we derive a new scheme to renormalize the sampled RDFs based on a model of the excluded volume of the particle-pairs they were sampled from, to emulate sampling from an infinite system. We compare this new correction method to two previous RDF-correction methods, developed for Kirkwood–Buff theory applications. We present a quantitative test to assess the reliability of the simulated low-q scattering signal and show that our RDF-correction successfully recovers the correct q = 0 limit for neat water. We investigate the effect of MD-sampling time on the RDF-corrections, before advancing to a molecular example system, comprised of a transition metal complex solvated in a series of water cells with varying densities. We show that our correction recovers the correct q = 0 behavior for all densities. Furthermore, we employ a simple continuum scattering model to dissect the total scattering signal from the solvent–solvent structural correlations in a solute–solvent model system to find two distinct contributions: a non-local density-contribution from the finite, fixed cell size in NVT simulations, and a local contribution from the solvent shell. We show how the second contribution can be approximated without also including the finite-size contribution. Finally, we provide a "best-practices"-checklist for experimentalists planning to incorporate explicit solvation MD simulations in future work, offering guidance for improving the accuracy and reliability of structural studies using x-ray scattering methods in solution. [ABSTRACT FROM AUTHOR]

While the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility. Here, we investigate the role of water influx in a prototypical migrating cell, the neutrophil, which undergoes rapid, directed movement to sites of injury, and infection. Chemoattractant exposure both increases cell volume and potentiates migration, but the causal link between these processes are not known. We combine single-cell volume measurements and a genome-wide CRISPR screen to identify the regulators of chemoattractant-induced neutrophil swelling, including NHE1, AE2, PI3K-gamma, and CA2. Through NHE1 inhibition in primary human neutrophils, we show that cell swelling is both necessary and sufficient for the potentiation of migration following chemoattractant stimulation. Our data demonstrate that chemoattractant-driven cell swelling complements cytoskeletal rearrangements to enhance migration speed.

The vertical migrations of pelagic organisms play a crucial role in shaping marine ecosystems and influencing global biogeochemical cycles. They also form the foundation of what might be the largest daily biomass movement on Earth. Surprisingly, among this diverse group of organisms, some single-cell protists can transit depths exceeding 50 m without employing flagella or cilia. How these non-motile cells perform large migrations remains unknown. It has been previously proposed that this capability might rely on the cell's ability to regulate its internal density relative to seawater. Here, using the dinoflagellate algae Pyrocystis noctiluca as a model system, we discover a rapid cell inflation event post cell division, during which a single plankton cell expands its volume 6-fold in less than 10 min. We demonstrate this rapid cellular inflation is the primary mechanism of density control. This self-regulated cellular inflation selectively imports fluid less dense than surrounding seawater and can thus effectively sling-shot a cell and reverse sedimentation within minutes. To accommodate its dramatic cellular expansion, Pyrocystis noctiluca possesses a unique reticulated cytoplasmic architecture that enables a rapid increase in overall cell volume without diluting its cytoplasmic content. We further present a generalized mathematical framework that unifies cell-cycle-driven density regulation, stratified ecology, and associated cell behavior in the open ocean. Our study unveils an ingenious strategy employed by a non-motile plankton to evade the gravitational sedimentation trap, highlighting how precise control of cell size and cell density can enable long-distance migration in the open ocean. • Pyrocystis noctiluca uses cellular inflation for vertical migration in the ocean • Calcium-triggered inflation rapidly alters cell density relative to seawater • A reticulated cytoplasmic network enables 6-fold volume increase without dilution • Mathematical model shows how inflation helps cells escape "gravitational traps" Larson et al. use field work, lab experiments, and theory to demonstrate that the non-motile dinoflagellate Pyrocystis noctiluca uses rapid cellular inflation to travel tens of meters in the ocean. This mechanism, enabled by a complex cytoplasmic organization, allows the cell to alter its density relative to seawater and reverse sedimentation. [ABSTRACT FROM AUTHOR]

The present research focuses on the electrical properties of lead-free piezoceramics (0.985- x)(K 0.485 Na 0.485 Li 0.03)(Nb 0.96 Sb 0.04)O 3 -0.015(Bi 0.5 Na 0.5)ZrO 3 - x SnO 2 (KNNLS-BNZ- x SnO 2 , x = 0.003, 0.006, 0.009, 0.012, and 0.015). This study examines the influence of varying SnO 2 doping levels on the microstructure and piezoelectric properties of the ceramics. All the ceramics prepared demonstrate pure perovskite structure without any secondary phases. The Rietveld refinement analysis of XRD data reveals the existence of multiphase evolution around room temperature. The tetragonality (c/a) and cell volume of the ceramics tend to rise with an increase in Sn4+ content, potentially leading to improved ferroelectric characteristics. The optimum values obtained were Curie temperature (T c) = 395 oC, remnant polarization (P r) = 21.07 μC/cm2, piezoelectric coefficient (d 33)=357 pC/N, piezoelectric voltage constant (g 33) = 24 × 10−3 Vm/N, and figure of merit (FOM off) = 10.34 pm2/N, corresponding to the ceramic doped with x = 0.012 SnO 2. The findings indicate that an optimal amount of Sn4+ in the host composition KNNLS-BNZ improves piezoelectric properties by constructing an R-O-T phase boundary near room temperature. This study suggests that the ceramic with x = 0.012 SnO 2 exhibits a favorably high T c coupled with an exceptional energy harvesting capability, making it a suitable candidate for energy harvesting applications. [ABSTRACT FROM AUTHOR]

Micro-CT imaging is a powerful tool for generating high-resolution, isotropic, three-dimensional datasets of whole, centimeter-scale model organisms. At histological resolutions, micro-CT can be used for whole-animal qualitative and quantitative characterization of tissue and organismal structure in health and disease. The small size, global freshwater distribution, wide range of cell size and structures of micron scale, and common use of Daphnia magna in toxicological and environmental studies make it an ideal model for demonstrating the potential power of micro-CT-enabled whole-organism phenotyping. This protocol details the steps involved in D. magna samples preparation for micro-CT, including euthanasia, fixation, staining, and resin embedding. Micro-CT reconstructions of samples imaged using synchrotron micro-CT reveal histological (microanatomic) features of organ systems, tissues, and cells in the context of the entire organism at sub-micron resolution and in 3D. The enabled "3D histology" and 3D renderings can be used for morphometric analyses across cells, tissues, and organ systems. [ABSTRACT FROM AUTHOR]

Background: Iron-deficiency is associated with increased morbidity and mortality in non-communicable diseases. However, iron parameters are rarely assessed in dogs. Here, we aimed to assess and correlate iron parameters in dogs suffering from Canine Atopic Dermatitis (CAD) compared to non-atopic, healthy dogs. Results: For this retrospective study, blood values and sera of 34 dogs with confirmed CAD were compared with 94 healthy non-atopic dogs. In our cohort, dogs with CAD had significantly lower mean corpuscular volume (MCV,) mean corpuscular hemoglobin (MCH) but higher white blood cell counts due to increased levels of circulating neutrophils and monocytes. CAD patients also had elevated total protein and c-reactive protein (CRP), but lower albumin levels compared to our healthy control dogs, indicated low-grade inflammation in the CAD cohort. Spearman correlations associated negatively clinical symptom (CADESI-4/PVAS) with MCV; ceruloplasmin and hepcidin, but positively with serum iron. Only in the CAD-cohort, MCV, CRP and albumin-levels negatively affected serum iron-levels and were positively associated with ceruloplasmin. Linear regression analysis revealed that serum iron-levels in CAD subjects, were positively dependent on hematocrit (packed cell volume, PCV) and albumin, and negatively dependent with white blood cells and neutrophils numbers. In contrast, in the healthy cohort, hepcidin was the sole factor associated with serum iron. Conclusions: A decreased iron status was associated with a higher symptom burden. Iron homeostasis differed markedly in healthy and atopic dermatitis dogs. CAD patients had depleted iron-stores and presented themselves with subclinical inflammation. [ABSTRACT FROM AUTHOR]

ABSTRACT Fine needle cytology (FNC) is a pivotal diagnostic tool for distinguishing between benign and malignant lymphadenopathies mainly because of its minimal invasiveness, cost‐effectiveness and accuracy. A major requirement for maximising diagnostic accuracy is proper sample management of aspirated cellular material. In this diagnostic process, the morphological evaluation of adequate smears is paramount, guiding cytopathologists in the selection of appropriate ancillary tests through the recognition of cell size and patterns of distribution. Here, we describe a peculiar ‘concentric ovals distribution pattern’, frequently observed in the FNC of benign reactive lymph nodes, which may represent an aid in the cytological diagnosis of reactive hyperplasia. [ABSTRACT FROM AUTHOR]

Key points Volume‐regulated anion channels (VRACs) formed by leucin‐rich repeat containing 8 (LRRC8) proteins play a pivotal role in regulatory volume decrease by mediating the release of chloride and organic osmolytes. Apart from the regulation of cell volume, LRRC8/VRAC function underlies numerous physiological processes in vertebrate cells including membrane potential regulation, glutamate release and apoptosis. LRRC8/VRACs are also permeable to antibiotics and anti‐cancer drugs, representing therefore important therapeutic targets. The activation mechanisms for LRRC8/VRACs are still unclear. Besides through osmotic cell swelling, LRRC8/VRACs can be activated by various stimuli under isovolumetric conditions. Sphingosine‐1‐phosphate (S1P), an important signalling lipid, which signals through a family of G protein‐coupled receptors (GPCRs), has been reported to activate LRRC8/VRACs in several cell lines. Here, we measured inter‐subunit Förster resonance energy transfer (FRET) and used whole‐cell patch clamp electrophysiology to investigate S1P‐induced LRRC8/VRAC activation. We systematically assessed the involvement of GPCRs and G protein‐mediated signal transduction in channel activation. We found that S1P‐induced channel activation is mediated by S1PR1 in HeLa cells. Following the downstream signalling pathway of S1PR1 and using toxin‐mediated inhibition of the associated G proteins, we showed that Gβγ dimers rather than Gαi or Gαq play a critical role in S1P‐induced VRAC activation. We could also show that S1P causes protein kinase D (PKD) phosphorylation, suggesting that Gβγ recruits phospholipase Cβ (PLCβ) with the consequent PKD activation by diacylglycerol. Notably, S1P did not activate LRRC8/VRAC in HEK293 cells, but overexpression of Gβγ‐responsive PLCβ isoform could facilitate S1P‐induced LRRC8/VRAC currents. We thus identified S1PR1‐mediated Gβγ‐PLCβ signalling as a key mechanism underlying isosmotic LRRC8/VRAC activation. Leucin‐rich repeat containing 8 (LRRC8) anion/osmolyte channels are involved in multiple physiological processes where they can be activated as volume‐regulated anion channels (VRACs) by osmotic cell swelling or isovolumetric stimuli such as sphingosine‐1‐phosphate (S1P). In the present study, using pharmacological modulation and gene‐depleted cells in patch clamp recording and optical monitoring of LRRC8 activity, we find that LRRC8/VRAC activation by S1P is mediated by the G protein‐coupled receptor S1PR1 coupled to G proteins of the Gi family. The signal transduction to LRRC8/VRAC activation specifically involves phospholipase Cβ activation by βγ subunits of pertussis toxin‐insensitive heteromeric Gi proteins. S1P‐mediated and hypotonicity‐induced LRRC8/VRAC activation pathways converge in protein kinase D activation. [ABSTRACT FROM AUTHOR]

Premise Methods Results Conclusions Nelumbo nucifera is one of several plant species with flowers that typically open in the early morning and close by noon. This movement normally repeats for 3 days, with all petals falling off on day 4. However, detailed observations of flower movement in Nelumbo species are limited.Movement of flowers on plants in growth chambers were observed using time‐lapse photography. Petals were examined with scanning electron microscopy or fixed and sectioned for light microscopy to determine whether changes in cell size contribute to petal elongation during flowering.This study is the first to microscopically observe petal cells of a Nelumbo species during flowering in controlled conditions. Petals elongated during the 4‐day flowering period. Inner petals were more elongated than the outer petals. Among the basal, central, and tip regions of a single petal, the cells in the basal region enlarged the most. Outer and inner epidermal cells in the basal region of the inner petals, on both adaxial and abaxial sides, gradually enlarged during the flowering period through cycles of repeated increases as the petals opened and decreases as they closed.Petals opened and closed repeatedly as they elongated, primarily in their basal region. Cells in the basal region of the petal on the adaxial and abaxial sides periodically fluctuated in size, increased during flower opening and decreased during closing, but differences in these patterns were observed between the two sides, suggesting that one of the driving forces behind the opening and closing of flowers of Nelumbo species is the increase and decrease in the size of the petal cells. [ABSTRACT FROM AUTHOR]

In plants, sugars are the key source of energy and metabolic building blocks. The systemic transport of sugars is essential for plant growth and morphogenesis. Plants evolved intricate molecular networks to effectively distribute sugars. The dynamic distribution of these osmotically active compounds is a handy tool for regulating cell turgor pressure, an instructive force in developmental biology. In this study, we have investigated the molecular mechanism behind the dual role of the receptor-like kinase CANAR. We functionally characterized a long non-coding RNA, CARMA , as a negative regulator of CANAR. Sugar-responsive CARMA specifically fine-tunes CANAR expression in the phloem, the route of sugar transport. Our genetic, molecular, microscopy, and biophysical data suggest that the CARMA–CANAR module controls the shoot-to-root phloem transport of sugars, allows cells to flexibly adapt to the external osmolality by appropriate water uptake, and thus adjust the size of vascular cell types during organ growth and development. Our study identifies a nexus of plant vascular tissue formation with cell internal pressure monitoring, revealing a novel functional aspect of long non-coding RNAs in developmental biology. This study shows that the CARMA–CANAR module acts as a novel osmoregulatory system controlling cell size in the root stele in response to external osmolality. CANAR activity regulates the shoot-to-root phloem transport of sugars, which influences internal pressure via cellular water uptake and thus cell size. [ABSTRACT FROM AUTHOR]

CRISPR-Cas12e is a recently identified gene-editing tool mainly known because its relatively small size benefits cell delivery. Drastically different from Cas9, it creates a blunt-end double-strand breakage of the DNA via two cleavage sites; Cas12e produces a sticky-end double-strand breakage of the DNA through only one cleavage site in its RuvC domain, meaning two consecutive cleavage events first on the non-target strand (ntsDNA) and then the target strand (tsDNA). Though crucial for Cas12e's cleavage efficiency, the mechanism by which Cas12e loads tsDNA for the second cleavage remains elusive. Through molecular dynamics simulations and our recently matured traveling-salesman-based automated path-searching (TAPS) algorithm, we identified a series of positively charged residues (Arg856TSL, Arg768RuvC, Lys898TSL, Arg904TSL, Arg764RuvC) that guide the tsDNA backbone toward the cleavage site of wild-type PlmCas12e. Further simulations of the R856L and R904L mutants supported such observations. More interestingly, we found the key role of Glu662RuvC in coordinating Arg764RuvC, preventing its occupation of the cleavage site, and facilitating tsDNA cleavage. Additional simulations confirmed that mutating Glu662RuvC to valine disabled such coordination and created a stable intermediate state with Arg764RuvC occupying the cleavage site before tsDNA loading. These insights, revealing an elaborate mechanism of cleavage facilitation, offer essential guiding principles for future rational engineering of Cas12e into more efficient gene-editing tools. [ABSTRACT FROM AUTHOR]

The new key biodiversity areas (KBA) standard is an important method for identifying regions of the planet‐hosting unique biodiversity. KBAs are identified through the implementation of threshold‐based criteria that can be applied to any target species and region. Current methods to rapidly assess the existence of potential KBAs in different areas of the planet still present important challenges, although they are needed to accelerate the KBA identification process for large numbers of species globally. We developed a methodology to scan geographical regions and detect potential KBAs under multiple criteria. We tested the methodology on 59 species of reptiles and amphibians in Italy through the application of selected KBA criteria. Potential KBAs were identified for multiple species under most criteria, covering 1.4%–12% of the study area, depending on analytical settings. Cell size used to identify KBAs played an important role in shaping the distribution of potential KBAs, also affecting the overlap between areas triggered by different criteria. New potential KBAs identified in this study are only partially coincident with current KBAs in Italy (previously identified for birds) and within the national protected areas. [ABSTRACT FROM AUTHOR]

The cell structure uniformity of microcellular polymers significantly impacts material performance, especially for low-porosity microcellular TPU used in chip polishing. The distribution of the cell structure of polishing pads directly affects the removal rate and process repeatability. Despite its importance, no quantitative method for evaluating cell structure uniformity has been reported in the literature. In this study, a digital image processing method that involves morphological operations of scanning electron microscopy (SEM) images, binarization, and cell localization, and the statistical evaluation of cell structure parameters was established to evaluate cell structure uniformity. A quantitative metric, the cell structure uniformity index (CUI), was calculated based on cell structure indices, incorporating the cell size index (Ud), the cell number index (Un), and the cell local spacing index (Ur). By establishing an ideal model and analyzing representative SEM images, the effectiveness and efficiency of the method for evaluating cell structure uniformity of microcellular TPU were successfully validated. The results demonstrated that low-porosity TPU foams exhibited relatively low cell structure uniformity compared to the ideal model. The heterogeneous nucleation process in TPU caused non-uniform cell structures due to the temporal and spatial non-homogeneities during the early cell nucleation process. As the cells grew, they merged and reduced the distance between them, resulting in improved cell structure uniformity. [ABSTRACT FROM AUTHOR]

Proteasome inhibitors have been applied to anticancer therapy by accumulating toxic misfolded proteins. However, chemical inactivation of proteasome generates aggresome, a Vimentin cage-enclosed subcellular structure quarantining HDAC6-Dynein-transported misfolded proteins before the protein toxicants are degraded by autophagy. Hence, aggresome may attenuate proteasome inhibitor drug-induced cytotoxicity. To solve the problem, it is imperative to characterize how cells assemble aggresome. By examining aggresomes in six cell lines, A549 cells were selectively studied for their bigger cell size and moderate aggresome-forming activity. Aggresome grew in size upon continuous exposure of A549 cells to proteasome inhibitor MG132 and reached a mature size around the 16th to 24th hour of treatment. Mechanistic studies revealed that NF-кB translocated to the nucleus in MG132-treated cells, and chemical activation or knockdown of NF-кB enhanced or prohibited aggresome assembly. Further analyses showed that NF-кB upregulated HDAC6, and HDAC6 maintained the Vimentin cage by interacting with Vimentin p72, a key modification of the intermediate filament contributing to aggresome formation. Remarkably, chemical inactivation of NF-кB synergized MG132-induced cell mortality. All the findings suggest that NF-кB dictates aggresome assembly via upregulating HDAC6, and NF-кB inhibitor may serve as a potential drug potentiating proteasome inhibitor medicine-induced cytotoxicity during the treatment of cancer cells. NEW & NOTEWORTHY: The study reveals a new mechanism guiding MG132-triggered aggresome formation. NF-кB is quickly activated upon exposure to MG132, and NF-кB upregulates the misfolded protein recognizing factor HDCA6. In addition to collecting misfolded proteins, HDAC6 also binds Vimentin and maintains the Vimentin cage, which quarantines toxic misfolded proteins and protects cells from being toxified by those protein toxicants. Therapeutically, chemical inactivation of NF-кB synergizes MG132-induced cytotoxicity, providing a new strategy to defeat cancers. [ABSTRACT FROM AUTHOR]

Cardiac regeneration in newborn rodents depends on the ability of pre-existing cardiomyocytes to proliferate and divide. This capacity is lost within the first week of postnatal development when these cells rapidly switch from hyperplasia to hypertrophy, withdraw from the cell cycle, become binucleated, and increase in size. How these dynamic changes in cell size and nucleation impact cardiomyocyte proliferative potential is not well understood. In this study, we innovate the application of a commercially available digital holographic imaging microscope, the Holomonitor M4, to evaluate the proliferative responses of mononucleated and binucleated cardiomyocytes after CHIR99021 treatment, a model proliferative stimulus. This system enables long-term label-free quantitative tracking of primary cardiomyocyte dynamics in real-time with single-cell resolution. Our results confirm that chemical inhibition of glycogen synthase kinase 3 with CHIR99021 promotes complete cell division of both mononucleated and binucleated cardiomyocytes with high frequency. Quantitative tracking of cardiomyocyte volume dynamics during these proliferative events revealed that both mononucleated and binucleated cardiomyocytes reach a similar size-increase threshold prior to attempted cell division. Binucleated cardiomyocytes attempt to divide with lower frequency than mononucleated cardiomyocytes, which may be associated with inadequate increases in cell size. By defining the interrelationship between cardiomyocyte size, nucleation, and cell cycle control, we may better understand the cellular mechanisms that drive the loss of mammalian cardiac regenerative capacity after birth. Digital holographic imaging enables quantitative label-free three-dimensional tracking of cardiomyocyte and non-cardiomyocyte dynamics in vitro. Cardiomyocytes reach a size-increase threshold prior to cell division, which may be impaired by binucleation. Created with BioRender.com. [Display omitted] • Digital holographic imaging enables quantitative label-free three-dimensional monitoring of primary cardiac cultures in vitro. • Primary cardiomyocytes can be readily distinguished from non-cardiomyocytes based on their larger size and slower motility. • Mononucleated and binucleated cardiomyocytes reach a common size-increase threshold prior to cell division. [ABSTRACT FROM AUTHOR]

The deformability of human red blood cells (RBCs), which comprise almost 99% of the cells in whole blood, is largely related not only to pathophysiological blood flow but also to the levels of intracellular compounds. Therefore, statistical estimates of the deformability of individual RBCs are of paramount importance in the clinical diagnosis of blood diseases. Although the microscale hydrodynamic interactions of individual RBCs lead to non-Newtonian blood rheology, there is no established method to estimate individual RBC deformability from the rheological data of RBC suspensions, and the possibility of this estimation has not been proven. To address this issue, we conducted an integrated analysis of a model of the rheology of RBC suspensions, coupled with macrorheological data of human RBCs suspended in plasma. Assuming a nonlinear curve of the relative viscosity of the suspensions as a function of the cell volume fraction, the statistical average of the membrane shear elasticity was estimated for individual intact RBCs or hardened RBCs. Both estimated values reproduced well the experimentally observed shear-thinning non-Newtonian behavior in these suspensions. We hereby conclude that our complementary approach makes it possible to estimate the statistical average of individual RBC deformability from macrorheological data obtained with usual rheometric tests. [ABSTRACT FROM AUTHOR]

Leaf traits are known as indicative of species functional properties in angiosperms. Fern fronds are little studied in this concern, especially ex situ. We studied leaf mesophyll structure, pigments and gas exchange in four fern species grown in a glasshouse—Sphaeropteris cooperi (terrestrial tree fern), Phlebodium aureum (semi‐epiphytic herbaceous), Asplenium australasicum (epiphytic shrubby) and Platycerium bifurcatum (epiphytic herbaceous). Saturated assimilation rate (Asat) decreased and intrinsic water use efficiency (iWUE) increased from a terrestrial tree fern to epiphytic ferns. Asat positively correlated with chloroplast number (Nchl/A) and their surface area per leaf area (Achl/A). iWUE negatively related to Nchl/A and chlorophyll/carotenoid ratio. Most differences between species were found in the mesophyll thickness (MT) and mesophyll cell volume (Vcell) with the smallest values in S. cooperi and the largest ones in P. bifurcatum. We found that photosynthetic limitations in ferns were related to the chloroplast photosynthetic activity rather than to Nchl/A or pigment content which did not differ from most angiosperms. Epiphytic ferns showed larger values of Vcell per cell and per chloroplast compared to angiosperms and tree ferns. We concluded that an increase in MT and Vcell in the studied ferns was not associated with photosynthetic performance, but was related to volumetric cytoplasm–chloroplast ratio meaningful to light absorption and the water‐storage function of fern fronds. [ABSTRACT FROM AUTHOR]

The aim of this research is to investigate experimentally and numerically the low-velocity impact behavior of foam-based composites reinforced with warp-knitted spacer fabric (WKSF). To prepare different foam-based composites, the structural parameters of WKSFs including cell size, position, and Z-fiber height were considered. A drop weight impact test with an initial energy of 5J was carried out to examine the low-velocity impact behavior of composites, followed by experimental analyses of Mises, shear, and normal stress on various composite components. Thereafter, the impact behavior of the composites was simulated using ABAQUS/CAE software. The comparison between experimental and numerical results showed a maximum error of 9.79% in predicting the acceleration of impactor. In addition, the results revealed significant stress disparities among samples. Stress analysis showed complex patterns across samples, emphasizing structural parameter influence on stress tolerance and load-bearing capabilities. Notably, Z-fibers displayed substantial stress tolerance, while the matrix predominantly undergoes shear stress. Consequently, the ideal structure for low-velocity impact applications includes small cell size, high thickness, and non-facing hexagonal cells. [ABSTRACT FROM AUTHOR]

The structures of two K-richterite crystals with the crystal chemical formulas (K0.44Na0.320.24)Σ=1(Ca1.18Na0.82)Σ=2Mg5Si8O22OH2 and (K0.83Na0.020.15)Σ=1(Ca1.11Na0.89)Σ=2Mg5Si8O22OH2 synthesized at a pressure of 3 GPa and a temperature of 1000°С in the MgSiO3 + CaMgSi2O6 + K2CO3 + Na2CO3 + CO2 + H2O system were studied by single-crystal X-ray analysis and Raman spectroscopy. The monoclinic cell parameters were obtained: a = 10.0256(5) and 9.9748(11) Å, b = 17.9874(7) and 17.9879(16) Å, c = 5.2687(3) and 5.2746(6) Å, Ve.c. = 916.17(18) and 918.52(8) Å3, β = 104.520(12)° and 104.821(5)°, sp. gr. С2/m (12), and Z = 2. The sites M(1), M(2), and M(3) are inhabited by Mg2+, while site M(4) is occupied simultaneously by Ca2+ and Na+. The Na+ cations not included in M(4) are located in position A, which also accommodates K+ cations. Raman spectroscopy made it possible to reveal vacancies in position A in both samples. The structure corresponds to the "ideal" structure of richterite group minerals. The unit cell volume of the measured crystals is directly proportional to the K content in position A. Based on the generalization of new and published data, an equation of the dependence of Vu.c. for amphiboles of the richterite Na(NaCa)Mg5Si8O22(OH)2–K-richterite K(NaCa)Mg5Si8O22(OH)2 series with a low tremolite component on the K content in position A is proposed. [ABSTRACT FROM AUTHOR]

The study of vessel trajectories (VTs) holds significant benefits for marine route management and resource development. VT segmentation serves as a foundation for extracting vessel motion primitives and enables analysis of vessel manoeuvring habits and behavioural intentions. However, existing methods relying on predefined behaviour patterns face high labelling costs, which hinder accurate pattern recognition. This paper proposes a self‐supervised vessel trajectory segmentation method (SS‐VTS), which segments VTs based on their inherent spatio‐temporal semantics. SS‐VTS adaptively divides VTs into cells of optimal size. Then, it extracts split points on different semantic levels from the multi‐dimensional feature sequence of the VTs using self‐supervised learning. Finally, spatio‐temporal distance fusion module is performed on split points to determine change points and obtain VT segments with multiple semantics. Experiments on a real automatic identification system datasets show that SS‐VTS achieves state‐of‐the‐art segmentation results compared to seven baseline methods. [ABSTRACT FROM AUTHOR]

This study investigates the cell structure control in 50% thermoplastic polyurethane (TPU) and 50% acrylonitrile butadiene styrene (ABS) blend foam using CO2 as a physical blowing agent, focusing on the effects of variable foaming parameters on the microstructure. Samples measuring 25 × 25 × 1 mm were produced and analyzed for foam structure. The foaming process involved saturating the samples with CO2 gas at pressures of 4, 5.5, and 7 MPa, followed by rapid pressure release and immersion in a hot glycerol bath. The foaming parameters included varied temperatures (80, 90, and 120°C) and times (5–80 s). Scanning electron microscope (SEM) analysis provided data on cell size and density. Results indicated that increasing the saturation pressure enhanced CO2 uptake in the ABS/TPU blend, with the CO2 uptake rate peaking early in the process. Higher foaming temperatures and extended foaming times led to increased cell size, cell density, and expansion ratio. These findings highlight the significant role of process parameters in controlling the cell structure of ABS/TPU blend foams, offering valuable insights into optimizing foam properties for industrial applications. Highlights: Optimization of foam parameters leads to cell structure control in ABS/TPU composite foams for industrial applications.Increasing saturation pressure significantly boosts CO2 uptake in ABS/TPU composite foams.Increasing the foaming temperature and duration leads to larger cell sizes, higher cell density, and greater expansion ratios in ABS/TPU composite foams. [ABSTRACT FROM AUTHOR]

Microalgae are microorganisms that in recent years have become protagonists in research because they are potential candidates for use in obtaining compounds of interest such as lipids, which may be transformed into bioenergy compounds like biodiesel. Nannochloropsis oculata is a marine microalga whose main characteristic is its high lipid content. In this work, the effect of salinity intensity on the growth of N. oculata was investigated in the photobioreactor batch cultures incubated with a salinity ranging from 20 to 40 ppt to analyze its growth profile and chlorophyll pigment to obtain dry biomass and biofuel produced as lipid extraction. The results indicated specific growth rate maximum values of 0.343 day-1, obtained at 35 ppt salinity. Chlorophyll pigment increases with salt concentration between 25 and 35 ppt. The total lipid extracted increases considerably at moderate salinities condition (25-35) ppt, the maximum dry biomass harvest and productivity, accomplished after the microalgae cultivation salinity at 30 ppt was 0.623 g/l and 62.3 mg/l respectively. Same applies to the maximum total lipid content and productivity, which was 221 mg/l and 22.1 mg/l. day, respectively. These findings show that a variety of salinities support optimal biomass yield and biochemical composition in N. oculata cultivation. Salinity monitoring is crucial for successful cultivation. Furthermore, the advantages of N. oculata microalga, including its large cell size (facilitating harvest and grazer tolerance) and its salinity resilience, should be considered. [ABSTRACT FROM AUTHOR]

The growing demand for high-speed wireless communication systems, coupled with increasing environmental complexities, has made Reconfigurable Intelligent Surfaces (RIS) a promising solution. This paper presents the design and development of a novel one-bit RIS array targeted at millimeter-wave (mm-wave) applications to address the challenges associated with path loss at high operating frequencies. The proposed RIS design features a compact unit cell size of 11x11 mm², achieved through a single-layer structure using a dielectric material with a permittivity of 3.38. An AlGaAs PIN diode serves as the control element, enabling tunability for high-frequency applications. The unit cell employs a circular dumbbell shape and is designed using the CST Simulator to operate at a center frequency of 32.8 GHz, with a wide bandwidth ranging from 30 to 35 GHz. The design provides a reflection phase shift of 180 degrees between the on and off states, with a high reflection amplitude in both states, ensuring efficient beamforming. This paper presents a step-by-step process for simulating the RIS and gradually increases the array size from 2x2 to 4x4, and eventually to 16x16. [ABSTRACT FROM AUTHOR]

Summary: In modelling two‐phase flows, accurate representation of interfaces is crucial. A class of methods for interface reconstruction are based on isosurface extraction, which involves a non‐iterative, interpolation based approach. These approaches have been shown to be faster by an order of magnitude than the conventional PLIC schemes. In this work, we present a new isosurface extraction based interface reconstruction scheme based on the Marching Cubes algorithm (MC), which is commonly used in computer graphics for visualizing isosurfaces. The MC algorithm apriori lists and categorizes all possible interface configurations in a single grid cell into a Look Up Table (LUT), which makes this approach fast and robust. We also show that for certain interface configurations, the inverse problem of obtaining the isovalue from the cell volume fraction is not surjective, and a special treatment is required while handling these cases. We then demonstrate the capabilities of the method through benchmark cases for 2D and 3D static/dynamic interface reconstruction. [ABSTRACT FROM AUTHOR]

Background: Immuno-hematological abnormalities are common among HIV infected individuals as well as patients with highly active antiretroviral therapy (HAART). However, the immuno-hematological outcome of Dolutegravir based antiretroviral therapy (ART) usage is not well investigated. Objectives: To assess hematological and immunological parameters among adult HIV patients before and after initiation of Dolutegravir based ART regimen at St. Peter Specialized Hospital, Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted from May to July 2021 at St. Peter Specialized Hospital among adult HIV patients. A total of 422 HIV patients on Dolutegravir based ART (combination of Dolutegravir/lamivudine/tenofovir disoproxil fumarate (DTG/3TC/TDF)) for a minimum of 3 months were selected using convenient sampling methods. Socio-demographic as well as clinical data of the participants was obtained using pre-tested structured questionnaires and a review of medical records. Hematological parameters such as CBC was obtained using Beckman coulter automated hematology analyzer and immunological parameters such as CD4 count were determined using BD FACS presto. Statistical analysis of the data was done using SPSS version 21. Paired t-test was used to compare dependent variables before and after initiation of the new HAART and binary logistic regression was used to determine predictors of immuno-hematological abnormalities. P-value < 0.05 was considered as statistically significant. Results: Of 422 adult HIV patients, about 273(64.7%) were females. The mean age of study participants was 42.2 years (±10.4SD). The mean white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), platelet distribution width (PDW), CD4 count, as well as lymphocyte percentage, neutrophil percentage, and platelet counts (PLT) were increased significantly(P<0.05) after 3 months of the Dolutegravir based therapy. While, red cell distribution width (RDW) and mean cell hemoglobin (MCH) were decreased (P<0.05) after the treatment. Other hematological parameters such as mean cell volume (MCV), hematocrit (HCT), mean cell hemoglobin concentration (MCHC), mean platelet volume (MPV) and platelet distribution width (PDW) showed no significant change. On the other hand, the most common hematological abnormalities identified after the new HAART were anemia (12.1%); followed by Leucopenia (11.3%), neutropenia (6%), and thrombocytopenia (4%). Anemia was associated with female sex (AOR = 7.8, 95% CI: 1.9–32.2, P<0.005) and WHO clinical stage III/IV (AOR = 16, 95% CI: 10.63–66.46, P<0.01). Conclusion: There was a significant change in certain immuno-hematological parameters such as WBC count, RBC count, PLT count, Hb, PDW, CD4 count, lymphocyte and neutrophil percentage after initiation of the Dolutegravir based therapy. Anemia was the most common hematological abnormality. Further studies are required to fully comprehend the outcome of the new treatment regimen on immuno-hematological parameters. [ABSTRACT FROM AUTHOR]

Background: Blastocyst morphology has been demonstrated to be associated with ploidy status. Existing artificial intelligence models use manual grading or 2D images as the input for euploidy prediction, which suffer from subjectivity from observers and information loss due to incomplete features from 2D images. Here we aim to predict euploidy in human blastocysts using quantitative morphological parameters obtained by 3D morphology measurement. Methods: Multi-view images of 226 blastocysts on Day 6 were captured by manually rotating blastocysts during the preparation stage of trophectoderm biopsy. Quantitative morphological parameters were obtained by 3D morphology measurement. Six machine learning models were trained using 3D morphological parameters as the input and PGT-A results as the ground truth outcome. Model performance, including sensitivity, specificity, precision, accuracy and AUC, was evaluated on an additional test dataset. Model interpretation was conducted on the best-performing model. Results: All the 3D morphological parameters were significantly different between euploid and non-euploid blastocysts. Multivariate analysis revealed that three of the five parameters including trophectoderm cell number, trophectoderm cell size variance and inner cell mass area maintained statistical significance (P < 0.001, aOR = 1.054, 95% CI 1.034–1.073; P = 0.003, aOR = 0.994, 95% CI 0.991–0.998; P = 0.010, aOR = 1.003, 95% CI 1.001–1.006). The accuracy of euploidy prediction by the six machine learning models ranged from 80 to 95.6%, and the AUCs ranged from 0.881 to 0.984. Particularly, the decision tree model achieved the highest accuracy of 95.6% (95% CI 84.9-99.5%) with the AUC of 0.978 (95% CI 0.882–0.999), and the extreme gradient boosting model achieved the highest AUC of 0.984 (95% CI 0.892-1.000) with the accuracy of 93.3% (95% CI 81.7-98.6%). No significant difference was found between different age groups using either decision tree or extreme gradient boosting to predict euploid blastocysts. The quantitative criteria extracted from the decision tree imply that euploid blastocysts have a higher number of trophectoderm cells, larger inner cell mass area, and smaller trophectoderm cell size variance compared to non-euploid blastocysts. Conclusions: Using quantitative morphological parameters obtained by 3D morphology measurement, the decision tree-based machine learning model achieved an accuracy of 95.6% and AUC of 0.978 for predicting euploidy in Day 6 human blastocysts. Trial registration: N/A. [ABSTRACT FROM AUTHOR]

ABSTRACT Grain size and grain weight are important determinants for grain yield. In this study, we identify a novel OsMAPK5–OsWRKY72 module that negatively regulates grain length and grain weight in rice. We found that loss‐of‐function of OsMAPK5 leads to larger cell size of the rice spikelet hulls and a significant increase in both grain length and grain weight in an indica variety Minghui 86 (MH86). OsMAPK5 interacts with OsMAPKK3/4/5 and OsWRKY72 and phosphorylates OsWRKY72 at T86 and S88. Similar to the osmapk5 MH86 mutants, the oswrky72 knockout MH86 mutants exhibited larger size of spikelet hull cells and increased grain length and grain weight, whereas the OsWRKY72‐overexpression MH86 plants showed opposite phenotypes. OsWRKY72 targets the W‐box motifs in the promoter of OsARF6, an auxin response factor involved in auxin signaling. Dual‐luciferase reporter assays demonstrated that OsWRKY72 activates OsARF6 expression. The activation effect of the phosphorylation‐mimicking OsWRKY72T86D/S88D on OsARF6 expression was significantly enhanced, whereas the effects of the OsWRKY72 phosphorylation‐null mutants were significantly reduced. In addition, auxin levels in young panicles of the osmapk5 and oswrky72 mutants were significantly higher than that in the wild‐type MH86. Collectively, our study uncovered novel connections of the OsMAPKK3/4/5‐OsMAPK5‐mediated MAPK signaling, OsWRKY72‐mediated transcription regulation, and OsARF6‐mediated auxin signaling pathways in regulating grain length and grain weight in an indica‐type rice, providing promising targets for molecular breeding of rice varieties with high yield and quality. [ABSTRACT FROM AUTHOR]

Antibody-dependent cellular phagocytosis (ADCP) has been implicated in protection against HIV-1. However, methods for measuring ADCP currently rely on the phagocytosis of gp120- or gp41-coated beads that do not reflect physiologically relevant conformations of the viral envelope glycoprotein or the size of a virus-infected cell. We therefore developed a novel approach for measuring ADCP of HIV-infected cells expressing natural conformations of Env. A monocytic cell line (THP-1 cells) or primary human monocytes were incubated with a CD4+ T cell line that expresses eGFP upon HIV-1 infection in the presence of antibodies and ADCP was measured as the accumulation of eGFP+ material by flow cytometry. The internalization of HIV-infected cells by monocytes was confirmed visually by image-capture flow cytometry. Cytoskeletal remodeling, pseudopod formation and phagocytosis were also observed by confocal microscopy. We found that potent broadly neutralizing antibodies (bnAbs), but not non-neutralizing antibodies (nnAbs), mediate efficient phagocytosis of cells infected with either primary or lab-adapted HIV-1. A nnAb to a CD4-inducible epitope of gp120 (A32) failed to enable ADCP of HIV-infected cells but mediated efficient phagocytosis of gp120-coated beads. Conversely, a bnAb specific to intact Env trimers (PGT145) mediated potent ADCP of HIV-infected cells but did not facilitate the uptake of gp120-coated beads. These results underscore the importance of measuring ADCP of HIV-infected cells expressing physiologically relevant conformations of Env and show that most antibodies that are capable of binding to Env trimers on virions to neutralize virus infectivity are also capable of binding to Env on the surface of virus-infected cells to mediate ADCP. Author summary: In addition to neutralizing virus-infectivity, antibodies that bind to the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) can recruit cells of the immune system to eliminate productively infected cells through a process known as antibody-dependent cellular phagocytosis (ADCP). ADCP occurs when an antibody bound to Env on the surface of an HIV-infected cell is recognized by a phagocytic cell, such as a monocyte, macrophage or neutrophil, and the phagocytic cell engulfs and destroys the virus-infected cell. ADCP has been implicated in protection against HIV-1. However, methods for measuring ADCP currently do not reflect physiologically relevant conformations of Env or the size of a virus-infected cell. We therefore developed a novel assay for measuring ADCP of HIV-infected cells expressing natural conformations of Env. Using this approach, we found that potent broadly neutralizing antibodies (bnAbs) that are capable of binding to functional Env trimers on virions to block HIV-1 infectivity can also mediate efficient phagocytosis of HIV-infected cells. However, non-neutralizing antibodies (nnAbs) that by definition cannot block viral infectivity exhibit little or no ADCP. These results stand in marked contrast to previous methods for measuring ADCP based on the internalization of beads coated with recombinant Env proteins, which show greater antibody-dependent phagocytosis by nnAbs. These results show that most antibodies that are able to neutralize HIV-1 infectivity are also able to direct the phagocytosis of HIV-infected cells and illustrate the importance of measuring ADCP of virus-infected cells expressing physiologically relevant conformations of Env. [ABSTRACT FROM AUTHOR]

Community trait variability can arise from the species, genotypic, or individual plastic level. Trait changes on these levels can occur simultaneously, interact, and potentially translate to community functioning. Thus, they are crucial to realistically predict community functional changes. Using a phytoplankton model community comprising a diatom and a coccolithophore each with nine genotypes varying in cell size, we conducted a selection experiment over 130 generations towards nutrient availability. According to our expectations, mean community cell size and total biomass increased with increasing nutrient availability. Interspecifically, these community level changes were driven by shifts in species composition towards the larger diatom. Changes caused by intraspecific shifts did not result from sorting according to genotypes' standing variation in cell size in the first place. Instead, intraspecific changes likely resulted from the selection for a highly plastic diatom genotype, which led to a phenotypic distribution with larger cells in high and smaller cells in lower nutrient concentrations. We suggest that besides interspecific species sorting, the evolution of size plasticity through genotype selection represented an intraspecific contribution to mean community size increase with increasing nutrient availability that ultimately translated to increased total biomass. Our results demonstrate that all three levels on which trait changes can occur, regulate phytoplankton community‐level functional changes and thus should be considered when predicting community change on ecological time scales. [ABSTRACT FROM AUTHOR]

New materials based on LaScO 3 , namely, were synthesized by the solid-phase method. The structure of the resulting complex oxides was refined. The electrical properties of the undoped, mono- and co-doped samples were determined by varying the temperature T and pH 2 O. All substituted samples were found to have the conductivity of several orders of magnitude higher relative to the parent phase. The maximum conductivity was observed for the Ba2+/Mg2+-co-doped sample due to high concentration of oxygen vacancies The possibility of phase formation and its electrical properties are greatly influenced by geometric parameters such as the ratio of the radii of the host- and the dopant-ion, the free cell volume, the critical radius. It has been demonstrated that the nature of the dopant affects the porosity of the samples. The investigated phases demonstrate good chemical stability in a CO 2 -saturated atmosphere. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective Design Setting Animals Methods Results Conclusions To investigate the frequency of perioperative acute kidney injury (AKI) in American Society of Anesthesiologists (SA) Grade I canine patients undergoing elective desexing using urine microscopy techniques and assess if pre‐ and intraoperative factors affect risk of developing AKI.Prospective observational clinical study conducted between September 2020 and October 2020.University teaching hospital.Thirty‐two female and four male dogs between 5 months and 5 years of age classified as ASA I undergoing elective desexing surgery.Urinalysis was performed preoperatively and 20–24 h postoperatively to identify markers of renal tubular injury (RTI), particularly the presence of granular and renal tubular epithelial cell (RTEC) casts on sediment analysis. Dogs underwent a full physical examination and a preoperative assessment including measurement of urine specific gravity (USG), packed cell volume (PCV), total plasma protein and serum creatinine (sCr) was conducted as a part of the desexing programme. Anaesthetic records were examined for any evidence of intraoperative hypotension, defined as a mean arterial pressure (MAP) of <60 mmHg for any duration of time. MAP was measured using an indirect oscillometric technique. For analysis, animals were subdivided into affected and nonaffected groups, with affected animals those that had postoperative increases in granular and RTEC casts. Categorical and comparative analyses were then performed between groups to identify associations of increased casts with pre‐, intra‐ and postoperative variables.A frequency of RTI of 5.6% was identified. This was accompanied by a significant association between increases in casts with total duration (p = 0.027) and number (p = 0.016) of hypotensive episodes.RTI is an anaesthetic consideration in ASA I veterinary patients undergoing elective desexing surgery. The identification of an association between the total duration and number of hypotensive episodes and the frequency of RTI highlights the importance of early detection of hypotension along with prompt and effective intervention in veterinary patients. [ABSTRACT FROM AUTHOR]

DYRK1A, a ubiquitously expressed kinase, is linked to the dominant intellectual developmental disorder, microcephaly, and Down syndrome in humans. It regulates numerous cellular processes such as cell cycle, vesicle trafficking, and microtubule assembly. DYRK1A is a critical regulator of organ growth; however, how it regulates organ growth is not fully understood. Here, we show that the knockdown of DYRK1A in mammalian cells results in reduced cell size, which depends on mTORC1. Using proteomic approaches, we found that DYRK1A interacts with the tuberous sclerosis complex (TSC) proteins, namely TSC1 and TSC2, which negatively regulate mTORC1 activation. Furthermore, we show that DYRK1A phosphorylates TSC2 at T1462, a modification known to inhibit TSC activity and promote mTORC1 activity. We also found that the reduced cell growth upon knockdown of DYRK1A can be rescued by overexpression of RHEB, an activator of mTORC1. Our findings suggest that DYRK1A inhibits TSC complex activity through inhibitory phosphorylation on TSC2, thereby promoting mTORC1 activity. Furthermore, using the Drosophila neuromuscular junction as a model, we show that the mnb, the fly homologs of DYRK1A, is rescued by RHEB overexpression, suggesting a conserved role of DYRK1A in TORC1 regulation. [ABSTRACT FROM AUTHOR]

ABSTRACT This paper presents the design of a single‐layer, double‐sided frequency selective surface (FSS) with bandpass characteristics at the S‐band (2.45 GHz) and C band (5.8 GHz) for sub‐6‐GHz Industrial Scientific and Medical (ISM) bands. The proposed FSS is based on the concept of complementary FSS that produces additional resonant modes. The FSS is constructed using an ultra‐thin microwave laminate with a thickness of 0.00076λeff calculated at the C‐band. The solid patch on the front side of the FSS unit cell is composed of an octagonal ring connected to four spiral arms while the slotted region on the rear side is complementary to the geometry on the front side. The unit cell size of the proposed FSS element is 0.087λeff × 0.087λeff. The FSS has an ultra‐low profile with at least 40% size reduction compared to the state‐of‐the‐art. The FSS element offers 11.12% (288 MHz) and 11.45% (650 MHz) at 2.45 GHz and 5.8 GHz, respectively, at x‐polarization while 5.8% (142 MHz) and 5.9% (342 MHz) bandwidth in the y‐polarization. The FSS element has a rotational symmetric structure offering enhanced polarization stability and angular independent operation for oblique incidences up to 80°. Furthermore, FSS operation is stable, which is evaluated and presented. The prototype bandpass FSS is fabricated, and the simulation results are validated in real‐time using experiments. [ABSTRACT FROM AUTHOR]

Background: After weaning, nursery pigs have difficulty digesting non-starch polysaccharides in their diets, which can result in growth and health problems. Among non-starch polysaccharides, β-mannan is easily found in various cereal grains that form the basis of livestock diets and interferes the digestion and utilization of nutrients. Supplementation of dietary β-mannanase in nursery diet can alleviate the negative effects on nutrient utilization efficiency caused by β-mannan and improve growth and health of pigs. This study was conducted to evaluate effects of dietary β-mannanase supplementation on growth performance, nutrient digestibility, intestinal morphology, fecal microbiota, and systemic immune responses of weaned pigs. Results: Dietary β-mannanase (MAN) improved average daily gain (P = 0.053), average daily feed intake (P < 0.05), and gain to feed ratio (P = 0.077) of pigs for 3 weeks after weaning and apparent total tract digestibility of crude protein (P = 0.060) and reduced post-weaning diarrhea (P < 0.05). The MAN did not affect the ileal morphology. Pigs fed with MAN had more diverse fecal microbiota based on the results of alpha diversity [the number of operational taxonomic units (OTUs; P = 0.061), Shannon (P = 0.071), and Simpson indices (P = 0.078)] and relative abundance of phylum Bacteroidetes (P = 0.064) and genus Prevotella (P < 0.05) than pigs fed control diet (CON). As a result of beta diversity, fecal microbiota was clustered (P < 0.05) into two distinct groups between dietary treatments. The MAN decreased (P < 0.05) packed cell volume (PCV), the number of white blood cells (WBC), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and cortisol of the pigs for 2 weeks after weaning compared with CON. Conclusion: Dietary β-mannanase reduced post-weaning diarrhea of pigs by positively modulating gut microbiota and attenuating systemic immune responses. [ABSTRACT FROM AUTHOR]

We developed a single cell amine analysis approach utilizing isobarically multiplexed samples of 6 individual cells along with analyte abundant carrier. This methodology was applied for absolute quantitation of amino acids and untargeted relative quantitation of amines in a total of 108 individual cells using nanoflow LC with high‐resolution mass spectrometry. Together with individually determined cell sizes, this provides accessible quantification of intracellular amino acid concentrations within individual cells. The targeted method was partially validated for 10 amino acids with limits of detection in low attomoles, linear calibration range covering analyte amounts typically from 30 amol to 120 fmol, and correlation coefficients (R) above 0.99. This was applied with cell sizes recorded during dispensing to determine millimolar intracellular amino acid concentrations. The untargeted approach yielded 249 features that were detected in at least 25 % of the single cells, providing modest cell type separation on principal component analysis. Using Greedy forward selection with regularized least squares, a sub‐selection of 100 features explaining most of the difference was determined. These features were annotated using MS2 from analyte standards and accurate mass with library search. The approach provides accessible, sensitive, and high‐throughput method with the potential to be expanded also to other forms of ultrasensitive analysis. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis.The study population comprised 800 patients, of which 400 had light‐chain CA (AL‐CA) and 400 had transthyretin CA (ATTR‐CA). MVO was present in 221 (27.6%) patients, and more common in ATTR‐CA than AL‐CA (124 [56.1%] vs. 97 [43.9%], p = 0.033). Patients with MVO had a more severe cardiac phenotype evidenced by higher N‐terminal pro‐brain natriuretic peptide (3516 ng/L [1944–6247] vs. 2508 ng/L [1203–5752], p < 0.001), worse global longitudinal strain (−10.5% [−12.6; −7.9] vs. −12.0% [−16.0; −8.9], p < 0.001), and higher extracellular volume (56% [51–61] vs. 50% [45–57], p < 0.001). Patients with AL‐CA and MVO had a higher serum troponin (86 ng/L [47–148] vs. 59 ng/L [44–78], p < 0.001), and higher T2 (53 ms [50–56] vs. 50 ms [48–52], p < 0.001), but lower extracellular volume (55% [50–60] vs. 58% [53–61], p = 0.008) and lower indexed myocyte cell volume (48.6 g/m2 [41.1–59.8] vs. 55.7 g/m2 [47.5–68.4], p < 0.001) than patients with ATTR‐CA and MVO. MVO was associated with an increased risk of mortality in the overall population (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03–1.59, p = 0.025), and the subgroup with AL‐CA (HR 1.59, 95% CI 1.17–2.17, p = 0.003) but not ATTR‐CA (HR 1.04, 95% CI 0.77–1.40, p = 0.814).Microvascular obstruction is common in CA and is related to markers of amyloid infiltration. MVO is associated with an increased risk of mortality in AL‐CA, but not in ATTR‐CA. This reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, oedema and myocyte death. [ABSTRACT FROM AUTHOR]

Deposition of monosodium urate and calcium pyrophosphate (MSU and CPP) micro-crystals is responsible for painful and recurrent inflammation flares in gout and chondrocalcinosis. In these pathologies, the inflammatory reactions are due to the activation of macrophages responsible for releasing various cytokines including IL-1β. The maturation of IL-1β is mediated by the multiprotein NLRP3 inflammasome. Here, we find that activation of the NLRP3 inflammasome by crystals and concomitant production of IL-1β depend on cell volume regulation via activation of the osmo-sensitive LRRC8 anion channels. Both pharmacological inhibition and genetic silencing of LRRC8 abolish NLRP3 inflammasome activation by crystals in vitro and in mouse models of crystal-induced inflammation. Activation of LRRC8 upon MSU/CPP crystal exposure induces ATP release, P2Y receptor activation and intracellular calcium increase necessary for NLRP3 inflammasome activation and IL-1β maturation. We identify a function of the LRRC8 osmo-sensitive anion channels with pathophysiological relevance in the context of joint crystal-induced inflammation. Formation of urate and calcium pyrophosphate micro-crystals is responsible for painful inflammatory flares in gout and chondrocalcinosis. Here the authors show that the osmo-sensitive LRRC8 anion channel is involved with macrophage inflammasome activation by crystals involving cell volume regulation and ATP release leading to P2Y receptor activation. [ABSTRACT FROM AUTHOR]

Many animals share a lifelong capacity to adapt their growth rates and body sizes to changing environmental food supplies. However, the cellular and molecular basis underlying this plasticity remains only poorly understood. We therefore studied how the sea anemones Nematostella vectensis and Aiptasia (Exaiptasia pallida) respond to feeding and starvation. Combining quantifications of body size and cell numbers with mathematical modelling, we observed that growth and shrinkage rates in Nematostella are exponential, stereotypic and accompanied by dramatic changes in cell numbers. Notably, shrinkage rates, but not growth rates, are independent of body size. In the facultatively symbiotic Aiptasia, we show that growth and cell proliferation rates are dependent on the symbiotic state. On a cellular level, we found that >7% of all cells in Nematostella juveniles reversibly shift between S/G2/M and G1/G0 cell cycle phases when fed or starved, respectively. Furthermore, we demonstrate that polyp growth and cell proliferation are dependent on TOR signalling during feeding. Altogether, we provide a benchmark and resource for further investigating the nutritional regulation of body plasticity on multiple scales using the genetic toolkit available for Nematostella. [ABSTRACT FROM AUTHOR]

Tissue morphogenesis remains poorly understood. In plants, a central problem is how the 3D cellular architecture of a developing organ contributes to its final shape. We address this question through a comparative analysis of ovule morphogenesis, taking advantage of the diversity in ovule shape across angiosperms. Here, we provide a 3D digital atlas of Cardamine hirsuta ovule development at single cell resolution and compare it with an equivalent atlas of Arabidopsis thaliana. We introduce nerve-based topological analysis as a tool for unbiased detection of differences in cellular architectures and corroborate identified topological differences between two homologous tissues by comparative morphometrics and visual inspection. We find that differences in topology, cell volume variation and tissue growth patterns in the sheet-like integuments and the bulbous chalaza are associated with differences in ovule curvature. In contrast, the radialized conical ovule primordia and nucelli exhibit similar shapes, despite differences in internal cellular topology and tissue growth patterns. Our results support the notion that the structural organization of a tissue is associated with its susceptibility to shape changes during evolutionary shifts in 3D cellular architecture. [ABSTRACT FROM AUTHOR]

Severe asthma is characterized by increased cell volume (hypertrophy) and enhanced contractile function (hyperresponsiveness) of the airway smooth muscle cells (ASMCs). The causative relationship and underlying regulatory mechanisms between them, however, have remained unclear. Here, we manipulated the single-cell volume of in vitro cultured human ASMCs to increase from 2.7 to 5.2 and 8.2 × 103 μm3 as a simulated ASMC hypertrophy by culturing the cells on micropatterned rectangular substrates with a width of 25 μm and length from 50 to 100 and 200 μm, respectively. We found that as the cell volume increased, ASMCs exhibited a pro-contractile function with increased mRNA expression of contractile proteins, increased cell stiffness and traction force, and enhanced response to contractile stimulation. We also uncovered a concomitant increase in membrane tension and Piezo1 mRNA expression with increasing cell volume. Perhaps more importantly, we found that the enhanced contractile function due to cell volume increase was largely attenuated when membrane tension and Piezo1 mRNA expression were downregulated, and an auto-regulatory loop between Piezo1 and YAP mRNA expression was also involved in perpetuating the contractile function. These findings, thus, provide convincing evidence of a direct link between hypertrophy and enhanced contractile function of ASMCs that was mediated via Piezo1 mRNA expression, which may be specifically targeted as a novel therapeutic strategy to treat pulmonary diseases associated with ASMC hypertrophy such as severe asthma. [ABSTRACT FROM AUTHOR]

SUMMARY: Cyst nematodes establish permanent feeding structures called syncytia inside the host root vasculature, disrupting the flow of water and minerals. In response, plants form WOX11‐mediated adventitious lateral roots at nematode infection sites. WOX11 adventitious lateral rooting modulates tolerance to nematode infections; however, whether this also benefits nematode parasitism remains unknown. Here, we report on bioassays using a 35S::WOX11‐SRDX transcriptional repressor mutant to investigate whether WOX11 adventitious lateral rooting promotes syncytium development and thereby female growth and fecundity. Moreover, we chemically inhibited cellulose biosynthesis to verify if WOX11 directly modulates cell wall plasticity in syncytia. Finally, we performed histochemical analyses to test if WOX11 mediates syncytial cell wall plasticity via reactive oxygen species (ROS). Repression of WOX11‐mediated transcription specifically enhanced the radial expansion of syncytial elements, increasing both syncytium size and female offspring. The enhanced syncytial hypertrophy observed in the 35S::WOX11‐SRDX mutant could be phenocopied by chemical inhibition of cellulose biosynthesis and was associated with elevated levels of ROS at nematode infection sites. We, therefore, conclude that WOX11 restricts radial expansion of nematode‐feeding structures and female growth and fecundity, likely by modulating ROS‐mediated cell wall plasticity mechanisms. Remarkably, this novel role of WOX11 in plant cell size control is distinct from WOX11 adventitious lateral rooting underlying disease tolerance. Significance Statement: In this study, we uncover a novel role for WOX11 in Arabidopsis, which may help plants cope with infections by endoparasitic cyst nematodes in the field. By controlling plant cell size, WOX11 significantly limits the expansion of nematode feeding sites, ultimately reducing nematode offspring size. [ABSTRACT FROM AUTHOR]

Efficient allocation of energy resources to key physiological functions allows living organisms to grow and thrive in diverse environments and adapt to a wide range of perturbations. To quantitatively understand how unicellular organisms utilize their energy resources in response to changes in growth environment, we introduce a theory of dynamic energy allocation that describes cellular growth dynamics by partitioning metabolizable energy into key physiological functions: growth, division, cell shape regulation, energy storage and loss through dissipation. By optimizing the energy flux for growth, we develop the equations governing the time evolution of cell morphology and growth rate in diverse environments. The resulting model accurately captures experimentally observed dependencies of bacterial cell size on growth rate, superlinear scaling of metabolic rate with cell size and predicts nutrient-dependent trade-offs between energy expended for growth, division and shape maintenance. By calibrating model parameters with experimental data for the model organism Escherichia coli, our model describes bacterial growth control in dynamic conditions, particularly during nutrient shifts and osmotic shocks. Integrating both the mechanical properties of the cell and underlying biochemical regulation, our model predicts the driving factors behind a wide range of observed morphological and growth phenomena with minimal added complexity. [ABSTRACT FROM AUTHOR]

Regenerative therapies, including the transplantation of spinal cord progenitor cells (SCPCs) derived from induced pluripotent stem cells (iPSCs), are promising treatment strategies for spinal cord injuries. However, the risk of tumorigenicity from residual iPSCs advocates an unmet need for rapid SCPCs safety profiling. Herein, a rapid (≈3000 cells min‐1) electrical‐based microfluidic biophysical cytometer is reported to detect low‐abundance iPSCs from SCPCs at single‐cell resolution. Based on multifrequency impedance measurements (0.3 to 12 MHz), biophysical features including cell size, deformability, membrane, and nucleus dielectric properties are simultaneously quantified as a cell is hydrodynamically stretched at a cross junction under continuous flow. A supervised uniform manifold approximation and projection (UMAP) model is further developed for impedance‐based quantification of undifferentiated iPSCs with high sensitivity (≈1% spiked iPSCs) and shows good correlations with SCPCs differentiation outcomes using two iPSC lines. Cell membrane opacity (day 1) is also identified as a novel early intrinsic predictive biomarker that exhibits a strong correlation with SCPC differentiation efficiency (day 10). Overall, it is envisioned that this label‐free and optic‐free platform technology can be further developed as a versatile cost‐effective process analytical tool to monitor or assess stem cell quality and safety in regenerative medicine. [ABSTRACT FROM AUTHOR]

Summary: Abscission is the shedding of plant organs in response to developmental and environmental cues. Abscission involves cell separation between two neighboring cell types, residuum cells (RECs) and secession cells (SECs) in the floral abscission zone (AZ) in Arabidopsis thaliana. However, the regulatory mechanisms behind the spatial determination that governs cell separation are largely unknown.The class I KNOTTED‐like homeobox (KNOX) transcription factor BREVIPEDICELLUS (BP) negatively regulates AZ cell size and number in Arabidopsis. To identify new players participating in abscission, we performed a genetic screen by activation tagging a weak complementation line of bp‐3. We identified the mutant ebp1 (enhancer of BP1) displaying delayed floral organ abscission.The ebp1 mutant showed a concaved surface in SECs and abnormally stacked cells on the top of RECs, in contrast to the precisely separated surface in the wild‐type. Molecular and histological analyses revealed that the transcriptional programming during cell differentiation in the AZ is compromised in ebp1. The SECs of ebp1 have acquired REC‐like properties, including cuticle formation and superoxide production.We show that SEPARATION AFFECTING RNA‐BINDING PROTEIN1 (SARP1) is upregulated in ebp1 and plays a role in the establishment of the cell separation layer during floral organ abscission in Arabidopsis. [ABSTRACT FROM AUTHOR]