Functional organization of the S. cerevisiae phosphorylation network.

Reversible protein phosphorylation is a signaling mechanism involved in all cellular processes. To create a systems view of the signaling apparatus in budding yeast, we generated an epistatic miniarray profile (E-MAP) comprised of 100,000 pairwise, quantitative genetic interactions, including virtually all protein and small-molecule kinases and phosphatases as well as key cellular regulators. Quantitative genetic interaction mapping reveals factors working in compensatory pathways (negative genetic interactions) or those operating in linear pathways (positive genetic interactions). We found an enrichment of positive genetic interactions between kinases, phosphatases, and their substrates. In addition, we assembled a higher-order map from sets of three genes that display strong interactions with one another: triplets enriched for functional connectivity. The resulting network view provides insights into signaling pathway regulation and reveals a link between the cell-cycle kinase, Cak1, the Fus3 MAP kinase, and a pathway that regulates chromatin integrity during transcription by RNA polymerase II.

Microbial communities drive flux of acid orange 7 and crystal violet dyes in water-sediment system.

Unchecked dye effluent discharge poses escalating environmental and economic concerns, especially in developing nations. While dyes are well-recognized water pollutants, the mechanisms of their environmental spread are least understood. Therefore, the present study examines the partitioning of Acid Orange 7 (AO7) and Crystal Violet (CV) dyes using water-sediment microcosms and reports that native microbes significantly affect AO7 decolorization and transfer. Both dyes transition from infused to pristine matrices, reaching equilibrium in a fortnight. While microbes influence CV partitioning, their role in decolorization is minimal, emphasizing their varied impact on the environmental fate of dyes. Metagenomic analyses reveal contrasting microbial composition between control and AO7-infused samples. Control water samples displayed a dominance of Proteobacteria (62%), Firmicutes (24%), and Bacteroidetes (9%). However, AO7 exposure led to Proteobacteria reducing to 57% and Bacteroidetes to 3%, with Firmicutes increasing to 34%. Sediment samples, primarily comprising Firmicutes (47%) and Proteobacteria (39%), shifted post-AO7 exposure: Proteobacteria increased to 53%, and Firmicutes dropped to 38%. At the genus level, water samples dominated by Niveispirillum (34%) declined after AO7 exposure, while Bacillus and Pseudomonas increased. Notably, Serratia and Sphingomonas, known for azo dye degradation, rose post-exposure, hinting at their role in AO7 decolorization. Conversely, sediment samples showed a decrease in the growth of Bacillus and an increase in that of Pseudomonas and Serratia. These findings emphasize the significant role of microbial communities in determining the environmental fate of dyes, providing insights on its environmental implications and management.

Microhabitat influences on phage-bacteria dynamics in an abandoned mine for ecorestoration.

Understanding the complex interactions between bacteriophages (phages) and bacteria within varied environmental niches is critical yet underexplored for improving microbe-assisted ecological restoration. This study investigates the influence of microhabitat heterogeneity within an abandoned mine on phage-bacteria interaction patterns, focusing on Pseudomonas-enriched bacterial communities. By isolating viral communities and purifying bacteria from soils of three distinct microhabitats, we assessed the regulatory role of environmental factors on these interactions, crucial for bacterial success in environmental applications. We characterized microhabitat variability by analyzing soil particle size fractions, minerals composition, and elemental content using X-ray diffraction and energy-dispersive X-ray analyses. 16S rRNA sequencing and cross-infection assays revealed that although bacterial communities across different microhabitats are taxonomically similar, their interaction patterns with phages are distinct. Phage communities showed nonselective infectivity across soil types, while bacterial communities exhibited selective adaptation, facilitating colonization across diverse microhabitats. Minerals such as mica, kaolinite, and hematite were found to increase phage infectivity, whereas mixed-layer clay correlated with early lysis. Additionally, higher levels of iron (Fe) and potassium (K) were linked to bacterial resistance strategies. Our findings highlight the importance of understanding asymmetric adaptive strategies between bacteria and phages, driven by microhabitat heterogeneity, for enhancing microbial-mediated nature-based restoration of degraded ecosystems.

Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4.

Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2(-/-)) mice showed a distinctly "leaky" gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2(-/-)Tlr4(-/-) mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.

Magnetic and Magnetocaloric Properties of the A2LnSbO6 Lanthanide Oxides on the Frustrated fcc Lattice.

Frustrated lanthanide oxides are promising candidates for cryogen-free magnetic refrigeration due to their suppressed ordering temperatures and high magnetic moments. While much attention has been paid to the garnet and pyrochlore lattices, the magnetocaloric effect in frustrated face-centered cubic (fcc) lattices remains relatively unexplored. We previously showed that the frustrated fcc double perovskite Ba2GdSbO6 is a top-performing magnetocaloric material (per mol Gd) because of its small nearest-neighbor interaction between spins. Here we investigate different tuning parameters to maximize the magnetocaloric effect in the family of fcc lanthanide oxides, A2LnSbO6 (A = {Ba2+, Sr2+} and Ln = {Nd3+, Tb3+, Gd3+, Ho3+, Dy3+, Er3+}), including chemical pressure via the A site cation and the magnetic ground state via the lanthanide ion. Bulk magnetic measurements indicate a possible trend between magnetic short-range fluctuations and the field-temperature phase space of the magnetocaloric effect, determined by whether an ion is a Kramers or a non-Kramers ion. We report for the first time on the synthesis and magnetic characterization of the Ca2LnSbO6 series with tunable site disorder that can be used to control the deviations from Curie-Weiss behavior. Taken together, these results suggest fcc lanthanide oxides as tunable systems for magnetocaloric design.

Sample Dependence of Magnetism in the Next-Generation Cathode Material LiNi0.8Mn0.1Co0.1O2.

We present a structural and magnetic study of two batches of polycrystalline LiNi0.8Mn0.1Co0.1O2 (commonly known as Li NMC 811), a Ni-rich Li ion battery cathode material, using elemental analysis, X-ray and neutron diffraction, magnetometry, and polarized neutron scattering measurements. We find that the samples, labeled S1 and S2, have the composition Li1-xNi0.9+x-yMnyCo0.1O2, with x = 0.025(2), y = 0.120(2) for S1 and x = 0.002(2), y = 0.094(2) for S2, corresponding to different concentrations of magnetic ions and excess Ni2+ in the Li+ layers. Both samples show a peak in the zero-field-cooled (ZFC) dc susceptibility at 8.0(2) K, but the temperature at which the ZFC and FC (field-cooled) curves deviate is substantially different: 64(2) K for S1 and 122(2) K for S2. The ac susceptibility measurements show that the transition for S1 shifts with frequency whereas no such shift is observed for S2 within the resolution of our measurements. Our results demonstrate the sample dependence of magnetic properties in Li NMC 811, consistent with previous reports on the parent material LiNiO2. We further establish that a combination of experimental techniques is necessary to accurately determine the chemical composition of next-generation battery materials with multiple cations.

Heteromoiré Engineering on Magnetic Bloch Transport in Twisted Graphene Superlattices.

Localized electrons subject to applied magnetic fields can restart to propagate freely through the lattice in delocalized magnetic Bloch states (MBSs) when the lattice periodicity is commensurate with the magnetic length. Twisted graphene superlattices with moiré wavelength tunability enable experimental access to the unique delocalization in a controllable fashion. Here, we report the observation and characterization of high-temperature Brown-Zak (BZ) oscillations which come in two types, 1/B and B periodicity, originating from the generation of integer and fractional MBSs, in the twisted bilayer and trilayer graphene superlattices, respectively. Coexisting periodic-in-1/B oscillations assigned to different moiré wavelengths are dramatically observed in small-angle twisted bilayer graphene, which may arise from angle-disorder-induced in-plane heteromoiré superlattices. Moreover, the vertical stacking of heteromoiré supercells in double-twisted trilayer graphene results in a mega-sized superlattice. The exotic superlattice contributes to the periodic-in-B oscillation and dominates the magnetic Bloch transport.

Peroxidases from an invasive Mesquite species for management and restoration of fertility of phenolic-contaminated soil.

Phenolics drive the global economy, but they also pose threats to soil health and plant growth. Enzymes like peroxidase have the potential to remove the phenolic contaminants from the wastewater; however, their role in restoring soil health and improving plant growth has not yet been ascertained. We fractionated efficient peroxidases (MPx) from leaves of an invasive species of Mesquite, Prosopis juliflora, and demonstrated its superiority over horseradish peroxidase (HRP) in remediating phenol, 3-chlorophenol (3-CP), and a mixture of chlorophenols (CP-M), from contaminated soil. MPx removes phenolics over a broader range of pH (2.0-9.0) as compared with HRP (pH: 7.0-8.0). In soil, replacing H2O2 with CaO2 further increases the phenolic removal efficiency of MPx (≥90% of phenol, ≥ 70% of 3-CP, and ≥90% of CP-M). MPx maintains ~4-fold higher phenolic removal efficiency than purified HRP even in soils with extremely high contaminant concentration (2 g phenolics/kg of soil), which is desirable for environmental applications of enzymes for remediation. MPx treatment restores soil biological processes as evident by key enzymes of soil fertility viz. Acid- and alkaline-phosphatases, urease, and soil dehydrogenase, and improves potential biochemical fertility index of soil contaminated with phenolics. MPx treatment also assists the Vigna mungo test plant to overcome toxicant stress and grow healthy in contaminated soils. Optimization of MPx for application in the field environment would help both in the restoration of phenolic-contaminated soils and the management of invasive Mesquite.

Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR.

BACKGROUND: Ketoconazole binds to and antagonizes pregnane X receptor (PXR) activation. RESULTS: Yeast high throughput screens of PXR mutants define a unique region for ketoconazole binding. CONCLUSION: Ketoconazole genetically interacts with specific PXR surface residues. SIGNIFICANCE: A yeast-based genetic method to discover novel nuclear receptor interactions with ligands that associate with surface binding sites is suggested. The pregnane X receptor (PXR) is a master regulator of xenobiotic metabolism, and its activity is critical toward understanding the pathophysiology of several diseases, including inflammation, cancer, and steatosis. Previous studies have demonstrated that ketoconazole binds to ligand-activated PXR and antagonizes receptor control of gene expression. Structure-function as well as computational docking analysis suggested a putative binding region containing critical charge clamp residues Gln-272, and Phe-264 on the AF-2 surface of PXR. To define the antagonist binding surface(s) of PXR, we developed a novel assay to identify key amino acid residues on PXR based on a yeast two-hybrid screen that examined mutant forms of PXR. This screen identified multiple "gain-of-function" mutants that were "resistant" to the PXR antagonist effects of ketoconazole. We then compared our screen results identifying key PXR residues to those predicted by computational methods. Of 15 potential or putative binding residues based on docking, we identified three residues in the yeast screen that were then systematically verified to functionally interact with ketoconazole using mammalian assays. Among the residues confirmed by our study was Ser-208, which is on the opposite side of the protein from the AF-2 region critical for receptor regulation. The identification of new locations for antagonist binding on the surface or buried in PXR indicates novel aspects to the mechanism of receptor antagonism. These results significantly expand our understanding of antagonist binding sites on the surface of PXR and suggest new avenues to regulate this receptor for clinical applications.

Methodologies to decipher the cell secretome.

The cell secretome is a collection of proteins consisting of transmembrane proteins (TM) and proteins secreted by cells into the extracellular space. A significant portion (~13-20%) of the human proteome consists of secretory proteins. The secretory proteins play important roles in cell migration, cell signaling and communication. There is a plethora of methodologies available like Serial Analysis of Gene Expression (SAGE), DNA microarrays, antibody arrays and bead-based arrays, mass spectrometry, RNA sequencing and yeast, bacterial and mammalian secretion traps to identify the cell secretomes. There are many advantages and disadvantages in using any of the above methods. This review aims to discuss the methodologies available along with their potential advantages and disadvantages to identify secretory proteins. This review is a part of a Special issue on The Secretome. This article is part of a Special Issue entitled: An Updated Secretome.

Deciphering the ecological impact of azo dye pollution through microbial community analysis in water-sediment microcosms.

The uncontrolled release of untreated dyeing wastewater into aquatic ecosystems poses global environmental risks. It alters native microbial communities and associated ecological processes, often going unnoticed. Therefore, the influence of acid orange 7 dye (AO7) contamination on the natural microbial community was investigated using a water-sediment microcosm. Compared to sterile microcosms, complete dye decolourization in natural microcosms showed microbial communities' significance in combating xenobiotic contamination. Proteobacteria dominated the water community, whereas Firmicutes dominated the sediment. AO7 exposure induced notable shifts in the structural composition of the bacterial community in both water and sediment. Niveispirillum exhibited a marked decrease, and Pseudomonas demonstrated a notable increase. The - 9.0 log2FC in Niveispirillum, a nitrogen-fixing bacterium, from 24.4% in the control to 0.1% post-treatment, may disrupt nutrient balance, plant growth, and ecosystem productivity. Conversely, elevated levels of Pseudomonas sp. resulting from azo dye exposure demonstrate its ability to tolerate and bioremediate organic pollutants, highlighting its resilience. Functional profiling via KEGG pathway analysis revealed differential expression patterns under AO7 stress. Specifically, valine, leucine, and isoleucine degradation pathways in water decreased by 52.2%, and cysteine and methionine metabolism ceased expression entirely, indicating reduced protein metabolism and nutrient bioavailability under dye exposure. Furthermore, in sediment, glutathione metabolism ceased, indicating increased oxidative stress following AO7 infusion. However, C5-branched dibasic acid metabolism and limonene and pinene degradation were uniquely expressed in sediment. Decreased methane metabolism exacerbates the effects of global warming on aquatic ecosystems. Further, ceased-butanoate metabolic pathways reflect the textile dye wastewater-induced adverse impact on ecological processes, such as organic matter decomposition, energy flow, nutrient cycling, and community dynamics that help maintain self-purification and ecological balance in river ecosystems. These findings underscore the critical need for more comprehensive environmental monitoring and management strategies to mitigate ecological risks posed by textile dyes in aquatic ecosystems, which remain unnoticed.

Ecological life strategies of microbes in response to antibiotics as a driving factor in soils.

Antibiotics as a selection pressure driving the evolution of soil microbial communities is not well understood. Since microbial functions govern ecosystem services, an ecological framework is required to understand and predict antibiotic-induced functional and structural changes in microbial communities. Therefore, metagenomic studies explaining the impacts of antibiotics on soil microbial communities were mined, and alterations in microbial taxa were analyzed through an ecological lens using Grimes's Competitor-Stress tolerator-Ruderal (CSR) model. We propose considering antibiotics as the primary abiotic factor mentioned in the CSR model and classifying non-susceptible microbial taxa as degraders, resistant, and resilient groups analogous to competitors, stress tolerators, and ruderal strategists, respectively. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were among the phyla harboring most members with antibiotic-resistant groups. However, some antibiotic-resistant microbes in these phyla could not only tolerate but also subsist solely on antibiotics, while others degraded antibiotics as a part of secondary metabolism. Irrespective of their taxonomic affiliation, microbes with each life strategy displayed similar phenotypic characteristics. Therefore, it is recommended to consider microbial functional traits associated with each life strategy while analyzing the ecological impacts of antibiotics. Also, potential ecological crises posed by antibiotics through changes in microbial community and ecosystem functions were visualized. Applying ecological theory to understand and predict antibiotics-induced changes in microbial communities will also provide better insight into microbial behavior in the background of emerging contaminants and help develop a robust ecological classification system of microbes.

Putative interactions between transthyretin and endosulfan II and its relevance in breast cancer.

The unregulated use of organochlorine pesticides (OCPs) has been linked to spread of breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in breast cancer patients than in healthy controls: p',p' dichloro diphenyl trichloroethane (DDT), p'p' dichloro diphenyl dichloroethane (DDD), endosulfan II, delta-hexachlorocyclohexane (dHCH), and heptachlor epoxide A (HTEA). According to the odds ratio analysis, these OCPs, which have been banned for decades, continue to raise the risk of cancer in Indian women. Proteomic analysis of plasma from estrogen receptor-positive breast cancer patients revealed 17 dysregulated proteins, but transthyretin (TTR) was three times higher than in healthy controls, which is further validated by enzyme-linked immunosorbent assays (ELISA). Molecular docking and molecular dynamics studies revealed a competitive affinity between endosulfan II and the thyroxine-binding site of TTR, pointing towards the significance of the competition between thyroxin and endosulfan, resulting in endocrine disruption leading to breast cancer. Our study sheds light on the putative role of TTR in OCP-mediated BC, but more research is needed to decipher the underlying mechanisms that can be used to prevent the carcinogenic effects of these pesticides on women's health.

Free-Spin Dominated Magnetocaloric Effect in Dense Gd3+ Double Perovskites.

Frustrated lanthanide oxides with dense magnetic lattices are of fundamental interest for their potential in cryogenic refrigeration due to a large ground state entropy and suppressed ordering temperatures but can often be limited by short-range correlations. Here, we present examples of frustrated fcc oxides, Ba2GdSbO6 and Sr2GdSbO6, and the new site-disordered analogue Ca2GdSbO6 ([CaGd] A [CaSb] B O6), in which the magnetocaloric effect is influenced by minimal superexchange (J 1 ∼ 10 mK). We report on the crystal structures using powder X-ray diffraction and the bulk magnetic properties through low-field susceptibility and isothermal magnetization measurements. The Gd compounds exhibit a magnetic entropy change of up to -15.8 J/K/molGd in a field of 7 T at 2 K, a 20% excess compared to the value of -13.0 J/K/molGd for a standard in magnetic refrigeration, Gd3Ga5O12. Heat capacity measurements indicate a lack of magnetic ordering down to 0.4 K for Ba2GdSbO6 and Sr2GdSbO6, suggesting cooling down through the liquid 4-He regime. A mean-field model is used to elucidate the role of primarily free-spin behavior in the magnetocaloric performance of these compounds in comparison to other top-performing Gd-based oxides. The chemical flexibility of the double perovskites raises the possibility of further enhancement of the magnetocaloric effect in the Gd3+ fcc lattices.

Microbial fuel cells for mineralization and decolorization of azo dyes: Recent advances in design and materials.

Microbial fuel cells (MFCs) exhibit tremendous potential in the sustainable management of dye wastewater via degrading azo dyes while generating electricity. The past decade has witnessed advances in MFC configurations and materials; however, comprehensive analyses of design and material and its association with dye degradation and electricity generation are required for their industrial application. MFC models with high efficiency of dye decolorization (96-100%) and a wide variation in power generation (29.4-940 mW/m2) have been reported. However, only 28 out of 104 studies analyzed dye mineralization - a prerequisite to obviate dye toxicity. Consequently, the current review aims to provide an in-depth analysis of MFCs potential in dye degradation and mineralization and evaluates materials and designs as crucial factors. Also, structural and operation parameters critical to large-scale applicability and complete mineralization of azo dye were evaluated. Choice of materials, i.e., bacteria, anode, cathode, cathode catalyst, membrane, and substrate and their effects on power density and dye decolorization efficiency presented in review will help in economic feasibility and MFCs scalability to develop a self-sustainable solution for treating azo dye wastewater.

Extranodal histiocytic sarcoma mimicking colorectal lymphoma: Case report and review of literature.

Histiocytic sarcoma is a rare malignant neoplasm that demonstrates mature histiocytic traits as characterized by immunohistochemistry. We report a case of extranodal histiocytic sarcoma (ENHS) of colon in a 56-year-old man presenting with gastrointestinal symptoms. Radiological findings were indicative of lymphoma or diffuse metastatic disease in colon. Histopathology of colectomy specimen was suggestive of ENHS, and immunohistochemical studies confirmed the uncommon diagnosis. The patient refused further therapy and succumbed to systemic complications of metastatic disease within a month of diagnosis. There have only been seven previous reports in world literature of ENHS involving large intestine.

Emergent order in the kagome Ising magnet Dy3Mg2Sb3O14.

The Ising model-in which degrees of freedom (spins) are binary valued (up/down)-is a cornerstone of statistical physics that shows rich behaviour when spins occupy a highly frustrated lattice such as kagome. Here we show that the layered Ising magnet Dy3Mg2Sb3O14 hosts an emergent order predicted theoretically for individual kagome layers of in-plane Ising spins. Neutron-scattering and bulk thermomagnetic measurements reveal a phase transition at ∼0.3 K from a disordered spin-ice-like regime to an emergent charge ordered state, in which emergent magnetic charge degrees of freedom exhibit three-dimensional order while spins remain partially disordered. Monte Carlo simulations show that an interplay of inter-layer interactions, spin canting and chemical disorder stabilizes this state. Our results establish Dy3Mg2Sb3O14 as a tuneable system to study interacting emergent charges arising from kagome Ising frustration.