Browse Articles

Spatial population dynamics of bacterial colonies with social antibiotic resistance

Bacteria frequently inhabit surface-attached communities where rich “social” interactions can significantly alter their population-level behavior, including their response to antibiotics. Understanding these collective effects in spatially heterogeneous communities is an ongoing challenge. Here, we investigated the spatial organization that emerges from antibiotic exposure in initially randomly distributed communities containing antibiotic-resistant and -sensitive strains of Enterococcus faecalis , an opportunistic pathogen. We identified that a range of complex spatial structures emerged in the population homeland—the inoculated region that microbes inhabit prior to range expansion—which depended on initial colony composition and antibiotic concentration. We found that these arrangements were explained by cooperative interactions between resistant and sensitive subpopulations with a variable spatial scale, the result of dynamic zones of protection afforded to sensitive cells by growing populations of enzyme-producing resistant neighbors. Using a combination of experiments and mathematical models, we explored the complex spatiotemporal interaction dynamics that create these patterns, and predicted spatial arrangements of sensitive and resistant subpopulations under new conditions. We illustrated how spatial population dynamics in the homeland affect subsequent range expansion, both because they modulate the composition of the initial expanding front, and through long-range cooperation between the homeland and the expanding region. Finally, we showed that these spatial constraints resulted in populations whose size and composition differed markedly from matched populations in well-stirred (planktonic) cultures. These findings underscore the importance of spatial structure and cooperation, long-studied features in theoretical ecology, for determining the fate of bacterial communities under antibiotic exposure.

ERS regulates endometrial epithelial cell autophagy through XBP1s-mediated activation of the PI3K/AKT pathway

The antimicrobial activity of ETD151 defensin is dictated by the presence of glycosphingolipids in the targeted organisms

Fungal infections represent a significant global health concern, with a growing prevalence of antifungal drug resistance. Targeting glucosylceramides (GlcCer), which are functionally important glycosphingolipids (GSL) present in fungal membranes, represents a promising strategy for the development of antifungal drugs. GlcCer are associated with the antifungal activity of certain plant and insect defensins. The 44-residue ETD151 peptide, optimized from butterfly defensins, is active against several fungal pathogens. ETD151 has been shown to induce a multifaceted mechanism of action (MOA) in Botrytis cinerea , a multiresistant phytopathogenic fungus. However, the target has yet to be identified. Our findings demonstrate that the presence of GlcCer in membranes determines the susceptibility of Pichia pastoris and Candida albicans toward ETD151. To ascertain whether this is due to direct molecular recognition, we demonstrate that ETD151 selectively recognizes liposomes containing GlcCer from B. cinerea , which reveals a methylated-sphingoid base structure. The dissociation constant was estimated by microscale thermophoresis to be in the µM range. Finally, fluorescence microscopy revealed that ETD151 localizes preferentially at the surface of B. cinerea . Furthermore, the majority of prokaryotic cells do not contain GSL, which explains their resistance to ETD151. We investigated the susceptibility of Novosphingobium capsulatum , one of the rare GSL-containing bacteria, to ETD151. ETD151 demonstrated transient morphological changes and inhibitory growth activity (IC 50 ~75 µM) with an affinity for the cell surface, emphasizing the critical importance of GSL as target. Understanding the MOA of ETD151 could pave the way for new perspectives in human health and crop protection.

Innovative adaptive edge detection for noisy images using wavelet and Gaussian method

Unequal resource division occurs in the absence of group division and identity

Based on the seminal minimal group experiment, the widely influential social identity theory has, in the last 45 y, led to the belief that discrimination follows from intergroup relations and social identity. A large body of research evidenced that people discriminate against members of their out versus ingroup, even if groups and identities were assigned on the basis of a quantity estimate, aesthetic judgment, or a chance outcome. But to what extent may unequal resource division be accounted for by ad hoc difference versus sameness, outside of any group division? We show via Bayesian regression analyses in seven preregistered experiments (>1,400 subjects) that unequal resource division strategies persist against a single person that demonstrates a different versus the same quantity estimate, painting preference, or even coin flip (Experiments 1, 2, and 3ab), with 43.1% more money awarded for sameness relative to difference conditions (Experiments 4, 5, and 6). These findings open up the possibility that one key driver of discrimination may exist in a mechanism of interindividual comparison that treats ad hoc difference more negatively than ad hoc sameness. If unequal resource division readily emerges against a single person even after a mere chance difference, discrimination may be more widespread and occur for partly different reasons than is currently assumed. Theoretical implications for understanding cognitive and brain systems of discrimination are discussed.

A sensitive chalcogenide-based electrochemical sensor for ultra-level detection of Mospilan residues in real samples

Abstract Addressed herein, the synthetic bismuthinite and bismuthinite@copper sulphide as two metal chalcogenides have been applied for modifying a glassy carbon electrode(GCE). The as-prepared nanomaterials were characterized using X-ray diffraction (XRD), scanning electron microscopy(SEM) and Energy-dispersive X-ray spectroscopy(EDX). By comparing the results, bismuthinite @copper sulphide hybridized with graphene oxide (GO) modified electrode exhibited superior sensitivity for detection ultra-levels of pesticide Mospilan (acetamiprid) in real samples. The dynamic concentration range of acetamiprid was found to be 80-680nM with a remarkably low detection limit about 4.1nM along with good stability and repeatability. Finally, the fabricated electrochemical sensor, bismuthinite@copper sulphide/GO, was suggested as a suitable alternative to more complex enzyme-based and aptamer-based methods for Mospilan detection.

Liver-specific transgenic expression of human NTCP in rhesus macaques confers HBV susceptibility on primary hepatocytes

Hepatitis B virus (HBV) poses a significant global health challenge, necessitating the urgent development of curative therapeutics. However, this progress is impeded by the lack of robust, immunocompetent preclinical animal models due to HBV’s strict species specificity. We previously showed that vector-mediated expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), renders macaques fully susceptible to HBV infection. In this study, we have generated transgenic macaques expressing hNTCP, marking the creation of the first transgenic nonhuman primate model for infectious disease research. We used PiggyBac (PB) transposon technology to insert a liver-specific hNTCP expression cassette into rhesus macaque zygotes and transferred the resulting embryos into surrogate females, resulting in two healthy transgenic offspring. In both animals, hNTCP is highly and selectively expressed in the liver. Most importantly, we show that isolated hepatocytes from these monkeys are susceptible to HBV infection. These findings lay the foundation for the development of a nonhuman primate HBV model, facilitating the advancement and validation of curative HBV therapies.

Optimizing sustainable energy management in grid connected microgrids using quantum particle swarm optimization for cost and emission reduction

Deliberation during online bargaining reveals strategic information

A standard assumption in game theory is that decision-makers have preplanned strategies telling them what actions to take for every contingency. In contrast, nonstrategic decisions often involve an on-the-spot comparison process, with longer response times (RT) for choices between more similarly appealing options. If strategic decisions also exhibit these patterns, then RT might betray private information and alter game theory predictions. Here, we examined bargaining behavior to determine whether RT reveals private information in strategic settings. Using preexisting and experimental data from eBay, we show that both buyers and sellers take hours longer to accept bad offers and to reject good offers. We find nearly identical patterns in the two datasets, indicating a causal effect of offer size on RT. However, this relationship is half as strong for rejections as for acceptances, reducing the amount of useful private information revealed by the sellers. Counter to our predictions, buyers are discouraged by slow rejections—they are less likely to counteroffer to slow sellers. We also show that a drift-diffusion model (DDM), traditionally limited to decisions on the order of seconds, can account for decisions on the order of hours, sometimes days. The DDM reveals that more experienced sellers are less cautious and more inclined to accept offers. In summary, strategic decisions are inconsistent with preplanned strategies. This underscores the need for game theory to incorporate RT as a strategic variable and broadens the applicability of the DDM to slow decisions.

Adsorption of Au(III), Pt(IV), Pd(II), and Rh(III) ions on activated carbon in a batch reactor supported by microwave radiation

Osteocyte connexin hemichannels and prostaglandin E ₂ release dictate bone marrow mesenchymal stromal cell commitment

Bone is a dynamic organ constantly undergoing remodeling with both bone formation and resorption. Bone formation is mediated by osteoblasts originating from the differentiation of bone marrow (BM) mesenchymal stem and progenitor cells (BM-MSPCs). However, how bone cells communicate with BM-MSPCs to coordinate bone formation remains largely elusive. Here, we unveil a key role of osteocyte connexin 43 (Cx43) hemichannels in regulating the lineage commitment of BM-MSPCs. Two transgenic mouse models expressing dominant negative Cx43 mutants in osteocytes were used: R76W (inhibiting gap junctions) and Δ130 to 136 (inhibiting both hemichannels and gap junctions). BM-MSPCs from Δ130 to 136 mice showed enhanced adipogenic differentiation and reduced osteogenic potential, leading to increased BM adipocytes. Flow cytometry and single-cell RNA sequencing revealed shifts in BM-MSPC subsets, less osteogenic-biased MSPCs, and more adipogenic-biased MSPCs in Δ130 to 136 mice. Conversely, R76W, with more functional hemichannels, exhibited effects similar to WT mice or even greater opposite effects than Δ130 to 136 mice. Prostaglandin E 2 (PGE 2 ), released from active Cx43 hemichannels, inhibited adipogenesis and promoted osteogenesis via the PGE 2 receptor EP4 and ERK1/2 signaling. Inhibition of Cx43 hemichannels or EP4 led to increased adipogenic-biased MSPCs. Moreover, administration of a Cx43(M1) antibody, which inhibits hemichannels, substantially increased BM adipocytes, accompanied by increased adipogenic-biased MSPCs, and decreased osteogenic-biased MSPCs. Our study highlights the pivotal role of osteocyte Cx43 hemichannels in BM-MSPC fate decision through PGE 2 release, providing insights into the precise and highly regulated communication between matrix-bound bone cells and BM-MSPCs, which dictates bone formation and remodeling.

Effects of stimulus polarity on the local evoked potential in auditory brainstem implant users

Abstract Auditory brainstem implants (ABI) can enable hearing sensation through electrical stimulation of the cochlear nucleus. The basic stimulation and signal coding strategies of the ABI are based on those of the cochlear implant. This may not always be optimal, and ABI-specific strategies may be preferred. In a cohort of ten ABI users, we examined the feasibility of measuring local evoked potentials (LEP) via fine-grained stimulation with a forward masking paradigm. We introduce a new baseline-dependent definition of LEP amplitude for analyzing the LEP amplitude growth function to obtain threshold stimulation levels and slope values. The processing of biphasic pulses by the cochlear nucleus and the influence of the leading phase polarity were examined. There were no statistically significant differences in LEP thresholds or slopes between cathodic and anodic leading pulses. LEP thresholds measured with cathodic leading pulses (r = 0.77, t 31 = 6.81, p < 0.0001) and anodic leading pulses (r = 0.70, t 27 = 45.14, p < 0.0001) correlated significantly with perceptual hearing thresholds. The correlation analysis was impacted by outlier values, especially in the case of LEP thresholds measured with anodic leading pulses. Cathodic leading pulses had significantly shorter LEP peak latencies (t 104.8 = 2.63, p < 0.01). These results show that the cathodic leading pulses are superior for eliciting LEPs. We suggest that cathodic leading pulses should be the basis for ABI-specific coding strategies.

Impairment of DET1 causes neurological defects and lethality in mice and humans

COP1 and DET1 are components of an E3 ubiquitin ligase that is conserved from plants to humans. Mammalian COP1 binds to DET1 and is a substrate adaptor for the CUL4A-DDB1-RBX1 RING E3 ligase. Transcription factor substrates, including c-Jun, ETV4, and ETV5, are targeted for proteasomal degradation to effect rapid transcriptional changes in response to cues such as growth factor deprivation. Here, we link a homozygous DET1 R26W mutation to lethal developmental abnormalities in humans. Experimental cryo-electron microscopy of the DET1 complex with DDB1 and DDA1, as well as co-immunoprecipitation experiments, revealed that DET1 R26W impairs binding to DDB1, thereby compromising E3 ligase function. Accordingly, human-induced pluripotent stem cells homozygous for DET1 R26W expressed ETV4 and ETV5 highly, and exhibited defective mitochondrial homeostasis and aberrant caspase-dependent cell death when differentiated into neurons. Neuronal cell death was increased further in the presence of Det1 -deficient microglia as compared to WT microglia, indicating that the deleterious effects of the DET1 p.R26W mutation may stem from the dysregulation of multiple cell types. Mice lacking Det1 died during embryogenesis, while Det1 deletion just in neural stem cells elicited hydrocephalus, cerebellar dysplasia, and neonatal lethality. Our findings highlight an important role for DET1 in the neurological development of mice and humans.

The effect of adipose tissue on transdermal monochromatic light presented to the human fetus using Monte Carlo simulations

<i>CASP8</i> intronic expansion identified by poly-glycine-arginine pathology increases Alzheimer’s disease risk

Alzheimer’s disease (AD) affects more than 10% of the population ≥65 y of age, but the underlying biological risks of most AD cases are unclear. We show anti-poly-glycine-arginine (a-polyGR) positive aggregates frequently accumulate in sporadic AD autopsy brains (45/80 cases). We hypothesize that these aggregates are caused by one or more polyGR-encoding repeat expansion mutations. We developed a CRISPR/deactivated-Cas9 enrichment strategy to identify candidate GR-encoding repeat expansion mutations directly from genomic DNA isolated from a-polyGR(+) AD cases. Using this approach, we isolated an interrupted (GGGAGA) n intronic expansion within a SINE-VNTR-Alu element in CASP8 ( CASP8 -GGGAGA EXP ). Immunostaining using a-polyGR and locus-specific C-terminal antibodies demonstrate that the CASP8 -GGGAGA EXP expresses hybrid poly(GR)n(GE)n(RE)n proteins that accumulate in CASP8 -GGGAGA EXP (+) AD brains. In cells, expression of CASP8 -GGGAGA EXP minigenes leads to increased p-Tau (Ser202/Thr205) levels. Consistent with other types of repeat-associated non-AUG (RAN) proteins, poly(GR)n(GE)n(RE)n protein levels are increased by stress. Additionally, levels of these stress-induced proteins are reduced by metformin. Association studies show specific aggregate promoting interrupted CASP8 -GGGAGA EXP sequence variants found in ~3.6% of controls and 7.5% AD cases increase AD risk [ CASP8 -GGGAGA-AD-R1; OR 2.2, 95% CI (1.5185 to 3.1896), P = 3.1 × 10 −5 ]. Cells transfected with a high-risk CASP8 -GGGAGA-AD-R1 variant show increased toxicity and increased levels of poly(GR)n(GE)n(RE)n aggregates. Taken together, these data identify polyGR(+) aggregates as a frequent and unexpected type of brain pathology in AD and CASP8 -GGGAGA-AD-R1 alleles as a relatively common AD risk factor. Taken together, these data support a model in which CASP8 -GGGAGA EXP alleles combined with stress increase AD risk.

Long-lasting sex-specific alteration in left ventricular cardiac transcriptome following gamma and simGCRsim radiation

Ratio-based indicators for cytosolic Ca ²⁺ with visible light excitation

Calcium ions (Ca 2+ ) play central roles in cellular physiology. Fluorescent indicators for Ca 2+ ions revolutionized our ability to make rapid, accurate, and highly parallel measurement of Ca 2+ concentrations in living cells. The use of ratio-based imaging with one particular indicator, fura-2, allowed practitioners to correct for a number of experimental confounds, including dye bleaching, variations in sample thickness, and fluctuations in illumination intensity. Ratio-based imaging with fura-2 was the most accurate and reliable method for measuring Ca 2+ concentrations. Two drawbacks to fura-2 exist. First, it requires ultraviolet (UV) excitation, which is more toxic to living cells than visible light. Second, our ability to use fura-2 for accurate, stable, ratio-based determinations of Ca 2+ concentration in living cells is fast becoming a method of the past. This is due, in part, because modern microscopes are phasing out the use of mercury arc lamps that provide the UV excitation needed for fura-2 imaging. To address this problem, we describe the design, synthesis, and cellular application of benzo[ b ]phosphole-based fluorescent Ca 2+ indicators for ratio-based imaging of Ca 2+ in living cells that can be used with modern light emitting diode (LED)-equipped fluorescence microscopes. We report isoCaRed-1Me, a Ca 2+ indicator that enables ratio-based imaging in immortalized cell lines, primary mammalian hippocampal neurons, and human-induced pluripotent stem cell–derived cardiomyocytes. These data show that isoCaRed-1Me will be useful for ratio-based Ca 2+ imaging using modern microscopes.

Development and clinical validation of a novel platelet count-based nomogram for predicting microvascular invasion in HCC

Downscaling mutualistic networks from species to individuals reveals consistent interaction niches and roles within plant populations

Species-level networks emerge as the combination of interactions spanning multiple individuals, and their study has received considerable attention over the past 30 y. However, less is known about the structure of interaction configurations within species, even though individuals are the actual interacting units in nature. We compiled 46 empirical, individual-based, interaction networks on plant-animal seed dispersal mutualisms, comprising 1,037 plant individuals across 29 species from various regions. We compared the structure of individual-based networks to that of species-based networks and, by extending the niche concept to interaction assemblages, we explored individual plant specialization. Using a Bayesian framework to account for uncertainty derived from sampling, we examined how plant individuals “explore” the interaction niche of their populations. Both individual-based and species-based networks exhibited high variability in network properties, lacking remarkable structural and topological differences between them. Within populations, frugivores’ interaction allocation among plant individuals was highly heterogeneous, with one to three frugivore species dominating interactions. Regardless of species or bioregion, plant individuals displayed a variety of interaction profiles across populations, with a consistently-small percentage of individuals playing a central role and exhibiting high diversity in their interaction assemblage. Plant populations showed variable mid to low levels of niche specialization; and individuals’ interaction niche “breadth” accounted for 70% of the population interaction diversity, on average. Our results highlight how downscaling from species to individual-based networks helps understanding the structuring of interactions within ecological communities and provide an empirical basis for the extension of niche theory to complex mutualistic networks.

Spatiotemporal dynamics of suspended sediment in coastal Mekong Delta: a hydrodynamic modelling approach under tropical monsoon climate

Abstract Suspended sediment concentration (SSC) plays a pivotal role in shaping coastal dynamics, impacting terrestrial and marine ecosystems. This study employed the hydrodynamic model MIKE21 to simulate hydrological runoff and sediment transport within the Mekong River’s fluvial-marine continuum, the longest river in Southeast Asia currently challenged with escalating anthropogenic pressures and sea-level rise. By strategically selecting hourly observed data from various locations (river channel, coastal estuary) and periods (dry and rainy seasons) for model calibration and validation, we demonstrated the robust performance of the model simulation of both water levels (RMSE: 0.343 m) and SSC (RMSE: 0.006 kg.m−3). Spatiotemporal analysis of 2019–2023 revealed the pronounced sensitivity of water level, velocity, and flow direction under tropical monsoon regime. SSC time series decomposition further extracted seasonal amplitudes, while spatial patterns showed distinctly the lowest concentrations occurring in April and the highest in September annually. Furthermore, SSC upward trends were observed during low-flow periods, while downward trends predominated during high-flow periods. Our quantitative analysis offers a comprehensive understanding of hydrological processes within tropical monsoon coastal regions. These findings support the establishment of long-term monitoring frameworks to inform nature-based strategies for sustainable coastal development.