Distinct Processes Research Articles

Comprehensive characterization of extracellular vesicles produced by environmental (Neff) and clinical (T4) strains of Acanthamoeba castellanii.

We conducted a comprehensive comparative analysis of extracellular vesicles (EVs) from two Acanthamoeba castellanii strains, Neff (environmental) and T4 (clinical). Morphological analysis via transmission electron microscopy revealed slightly larger Neff EVs (average = 194.5 nm) compared to more polydisperse T4 EVs (average = 168.4 nm). Nanoparticle tracking analysis (NTA) and dynamic light scattering validated these differences. Proteomic analysis of the EVs identified 1,352 proteins, with 1,107 common, 161 exclusive in Neff, and 84 exclusively in T4 EVs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping revealed distinct molecular functions and biological processes and notably, the T4 EVs enrichment in serine proteases, aligned with its pathogenicity. Lipidomic analysis revealed a prevalence of unsaturated lipid species in Neff EVs, particularly triacylglycerols, phosphatidylethanolamines (PEs), and phosphatidylserine, while T4 EVs were enriched in diacylglycerols and diacylglyceryl trimethylhomoserine, phosphatidylcholine and less unsaturated PEs, suggesting differences in lipid metabolism and membrane permeability. Metabolomic analysis indicated Neff EVs enrichment in glycerolipid metabolism, glycolysis, and nucleotide synthesis, while T4 EVs, methionine metabolism. Furthermore, RNA-seq of EVs revealed differential transcript between the strains, with Neff EVs enriched in transcripts related to gluconeogenesis and translation, suggesting gene regulation and metabolic shift, while in the T4 EVs transcripts were associated with signal transduction and protein kinase activity, indicating rapid responses to environmental changes. In this novel study, data integration highlighted the differences in enzyme profiles, metabolic processes, and potential origins of EVs in the two strains shedding light on the diversity and complexity of A. castellanii EVs and having implications for understanding host-pathogen interactions and developing targeted interventions for Acanthamoeba-related diseases.IMPORTANCEA comprehensive and fully comparative analysis of extracellular vesicles (EVs) from two Acanthamoeba castellanii strains of distinct virulence, a Neff (environmental) and T4 (clinical), revealed striking differences in their morphology and protein, lipid, metabolites, and transcripts levels. Data integration highlighted the differences in enzyme profiles, metabolic processes, and potential distinct origin of EVs from both strains, shedding light on the diversity and complexity of A. castellanii EVs, with direct implications for understanding host-pathogen interactions, disease mechanisms, and developing new therapies for the clinical intervention of Acanthamoeba-related diseases.

Enhanced detection of lysergic acid diethylamide using Ehrlich reagent and screen-printed electrodes: A hybrid method for application in forensic analysis

In forensic investigations, the presumptive identification of illicit substances, such as Lysergic Acid Diethylamide (LSD), is crucial. While the Ehrlich's colorimetric reagent (EHR) is commonly employed for LSD detection, producing a characteristic colour change, its lack of selectivity often leads to false-positive or misinterpreted results. Addressing this, we propose a novel method combining electrochemical detection with EHR, enhancing selectivity for LSD’s preliminary identification in forensic samples. This method utilizes a screen-printed carbon electrode (carbon-SPE) in a pH 12 phosphate buffer. We observed two irreversible oxidation processes for LSD at Epa= + 0.35 V (Ox1) and + 0.65 V (Ox2), and for EHR at + 0.62 V and + 0.83 V (vs Ag/AgCl). The LSD + EHR combination displayed three distinct irreversible oxidation processes at + 0.35 V, + 0.66 V, and + 0.86 V. This approach provides three analytical responses for LSD identification: (1) colour change post-EHR test; (2) voltammetric detection of LSD’s two oxidation processes on carbon-SPE; (3) decreased peak current of LSD at Ox1 post-reaction after EHR. Additionally, our method facilitates LSD quantification, exhibiting a low limit of detection (LOD) of 0.69 μmol/L, and consistent electrochemical responses (RSD < 3.0 %) using the same or different carbon-SPEs. Interference studies with other illicit drugs underscored the method’s reliability and selectivity in LSD detection. Moreover, addition-recovery studies on real seized samples approached 100 %, and LSD identification was corroborated by QTOF-LC/MS analyses. Therefore, combining voltammetry with carbon-SPE and EHR offers significant potential for a rapid, simple, and selective LSD screening test in forensic analysis.

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer.

The effect of anoikis-related genes (ARGs) on clinicopathological characteristics and tumor microenvironment remains unclear. We comprehensively analyzed anoikis-associated gene signatures of 1057 colorectal cancer (CRC) samples based on 18 ARGs. Anoikis-related molecular subtypes and gene features were identified through consensus clustering analysis. The biological functions and immune cell infiltration were assessed using the GSVA and ssGSEA algorithms. Prognostic risk score was constructed using multivariate Cox regression analysis. The immunological features of high-risk and low-risk groups were compared. Finally, DAPK2-overexpressing plasmid was transfected to measure its effect on tumor proliferation and metastasis in vitro and in vivo. We identified 18 prognostic ARGs. Three different subtypes of anoikis were identified and demonstrated to be linked to distinct biological processes and prognosis. Then, a risk score model was constructed and identified as an independent prognostic factor. Compared to the high-risk group, patients in the low-risk group exhibited longer survival, higher enrichment of checkpoint function, increased expression of CTLA4 and PD-L1, higher IPS scores, and a higher proportion of MSI-H. The results of RT-PCR indicated that the expression of DAPK2 mRNA was significantly downregulated in CRC tissues compared to normal tissues. Increased DAPK2 expression significantly suppressed cell proliferation, promoted apoptosis, and inhibited migration and invasion. The nude mice xenograft tumor model confirmed that high expression of DAPK2 inhibited tumor growth. Collectively, we discovered an innovative anoikis-related gene signature associated with prognosis and TME. Besides, our study indicated that DAPK2 can serve as a promising therapeutic target for inhibiting the growth and metastasis of CRC.

A novel low oxidation potential hydroxyurea sensor utilizing flower-shaped Zn and N co-doped porous carbon coupled with graphene oxide via one-step electrodeposition

Accurate monitoring of hydroxyurea (HU) dosage is imperative in the administration of anticancer drugs. Existing determination methods face challenges such as operational complexity, low sensitivity, or high oxidation potentials. In this study, a novel HU electrochemical sensor (Zn/N-PC/GO/GCE) was synthesized using flower-shaped Zn/N co-doped porous carbon (Zn/N-PC) with graphene oxide (GO) through a one-step electrodeposition. The sensor features a distinctive three-step oxidation process for HU with a low oxidation potential, attributed to an electrochemical activation electrode strategy and crucial Zn/N co-doping in Zn/N-PC. Three electrons involved oxidation process of HU and Zn/N-PC/GO adsorption energy through transferred electrons and density functional theory (DFT). Under optimized conditions, the sensor demonstrated a broad linear detection range (1–1000 μM) and an impressive limit of detection (LOD) of 0.52 μM. Applicability was confirmed by analyzing HU in tablet formulations, urine and serum samples. This study presents an innovative electrochemical method for accurate HU monitoring, elucidating a potential three-step oxidation mechanism.

Temperature and nutrients drive distinct successions between diatoms and dinoflagellates over the past 40 years: Implications for climate warming and eutrophication

Diatoms and dinoflagellates are two typical functional groups of phytoplankton, playing important roles in ecosystem processes and biogeochemical cycles. Changes in diatoms and dinoflagellates are thought to be one of the possible mechanisms for the increase in harmful algal blooms (HABs), due to changing hydrological conditions associated with climate change and human activities. However, little is known about their ability to adapt to changing ocean environments, thus making it difficult to know whether and how they are adapting. By analyzing a 44-year monitoring dataset in the central Bohai Sea during 1978–2021, we found that the abundance ratio of diatoms to dinoflagellates showed a decreasing trend seasonally and ecologically, indicating that the phytoplankton community underwent distinct successional processes from diatom dominance to diatom-dinoflagellate co-dominance. These processes exhibited varying responses to temperature, nutrient concentrations and ratios, and their interactions, of which temperature primarily drove the seasonal succession whereas nutrients were responsible for the ecological succession. Specifically, diatoms showed a preference for lower temperatures and higher DIP concentrations, and were able to tolerate lower DIN at lower temperatures. In contrast, dinoflagellates tended to prevail at conditions of warming and high N/P ratios. These different traits of diatoms and dinoflagellates reflected the fact that warming as a result of rising temperature and eutrophication as a consequence of nutrient input would favor dinoflagellates over diatoms. Moreover, the increasing dominance of dinoflagellates indicated that dinoflagellate blooms were likely to become more frequent and intense in the central Bohai Sea.

Abstract PO4-24-04: Identifying the interactome of TACC3, a major driver in aggressive cancer cells with centrosome amplification

Abstract Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) is a centrosome- and spindle-associated protein that drives the growth of highly aggressive tumors, such as those with centrosome amplification (CA). In recent years, it has become apparent that TACC3 not only functions at the centrosomes and spindles but may also have many other non-canonical functions facilitating the growth of tumors. Given the multifaceted roles of TACC3 in driving tumor aggressiveness, the identification of novel interactors of TACC3 that are responsible for mediating key TACC3-driven processes is crucial. This will not only uncover novel drug targets but will also expand the patient subpopulations that can benefit from TACC3 inhibition. Here, we characterized the cancer cells with CA in terms of their dependency on TACC3 for executing distinct cellular processes depending on the cell cycle phase. We demonstrated that TACC3 is strongly upregulated in cancers with CA at mRNA and protein levels and associated with worse clinical outcome in highly aggressive patient subpopulations, especially in TNBC. We further demonstrated that in mitotic cancer cells with CA, TACC3 is localized at the centrosomes in a complex with KIFC1, thus mediating the clustering of extra centrosomes to enable bipolar spindle formation and faithful mitosis. We showed that inhibiting TACC3 blocks the interaction between TACC3 and KIFC1, thus leading to mitotic cell death in the highly TACC3-dependent cancer cells with CA. While TACC3-KIFC1 complex is needed for mitotic cancer cells with CA, we found that in CA-bearing interphase cells, TACC3 interacts with HDAC2 and MBD2, the two major components of the chromatin remodeling NuRD complex within the nucleus. Inhibiting TACC3 prevented its nuclear localization, thus unloading the NuRD complex from the chromatin, leading to transcription of key tumor suppressors driving G1 arrest and apoptosis. To obtain the proteome-wide interaction network of TACC3 in these highly TACC3-dependent mitotic and interphase cancer cells with CA, we mapped the TACC3 interactome using the state-of-the-art APEX2 method. This uncovered potentially novel partners of TACC3 that could be critical for the survival of mitotic and interphase cancer cells with CA. We performed an extensive bioinformatic analysis to identify the most clinically relevant interactors in the context of cancers with CA. We generated correlation matrices of the mitotic and interphase-specific interactors and coupled them with pathway enrichment analysis to identify the key processes that the interactors are potentially involved in. Altogether, our results map, for the first time, the novel cell cycle-dependent TACC3 interactome in cancer cells with CA. Our results support targeting this multi-functional protein and hold great promise to improve clinical outcome in these highly aggressive cancers given the availability of the first-in-class IND-approved TACC3 inhibitor. Citation Format: Ozge Saatci, Ozge Akbulut, Metin Cetin, Vitali Sikirzhytski, Meral Uner, Deniz Lengerli, Elizabeth C. O’Quinn, Martin J. Romeo, Burcu Caliskan, Erden Banoglu, Sercan Aksoy, Aysegul Uner, Ozgur Sahin. Identifying the interactome of TACC3, a major driver in aggressive cancer cells with centrosome amplification [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-24-04.

Conventionality matters in Chinese metaphor but not simile comprehension: evidence from event-related potentials.

Metaphor and simile, two prevalent forms of figurative language widely employed in daily communication, serve as significant research subjects in linguistics. The Career of Metaphor Theory in cognitive linguistics posits that as conventionality increases, the cognitive mechanisms of metaphor comprehension shift from "comparison" to "categorization." In line with this notion, prior electrophysiological investigations have revealed that novel metaphors elicit a stronger N400 brain response compared to conventional metaphors. However, the observed N400 difference between conventional and novel metaphors may merely stem from the familiarity contrast between them, as conventional metaphors are typically more familiar than novel ones. To address this dichotomy, the present study not only compared the N400 responses between conventional and novel metaphors but also between conventional and novel similes. While conventional and novel similes differ in familiarity, similar to conventional and novel metaphors, both are processed via "comparison" mechanisms. The results revealed that novel metaphors elicited larger N400 amplitudes compared to conventional metaphors, aligning with previous findings. In contrast, no significant N400 differences were observed between conventional and novel similes, suggesting that familiarity disparity is unlikely to account for N400 distinctions. Our findings imply that conventional and novel metaphors undergo distinct cognitive processing mechanisms ("comparison" versus "categorization"), thereby providing further empirical validation for the Career of Metaphor Theory.

Distinct neural markers of evidence accumulation index metacognitive processing before and after simple visual decisions.

Perceptual decision-making is affected by uncertainty arising from the reliability of incoming sensory evidence (perceptual uncertainty) and the categorization of that evidence relative to a choice boundary (categorical uncertainty). Here, we investigated how these factors impact the temporal dynamics of evidence processing during decision-making and subsequent metacognitive judgments. Participants performed a motion discrimination task while electroencephalography was recorded. We manipulated perceptual uncertainty by varying motion coherence, and categorical uncertainty by varying the angular offset of motion signals relative to a criterion. After each trial, participants rated their desire to change their mind. High uncertainty impaired perceptual and metacognitive judgments and reduced the amplitude of the centro-parietal positivity, a neural marker of evidence accumulation. Coherence and offset affected the centro-parietal positivity at different time points, suggesting that perceptual and categorical uncertainty affect decision-making in sequential stages. Moreover, the centro-parietal positivity predicted participants' metacognitive judgments: larger predecisional centro-parietal positivity amplitude was associated with less desire to change one's mind, whereas larger postdecisional centro-parietal positivity amplitude was associated with greater desire to change one's mind, but only following errors. These findings reveal a dissociation between predecisional and postdecisional evidence processing, suggesting that the CPP tracks potentially distinct cognitive processes before and after a decision.

Between forests and coasts: Fishworkers on the move in India

AbstractThe Covid‐19 lockdown in India in March 2020 revealed the presence of Adivasi communities in the marine fishing industry of Goa, a coastal state in India. While the migration for work of Adivasi communities from the central regions of the country is well recorded, their movement across geographies of the forest and the coast is relatively unknown. Working with initial data collected during the lockdown, interviews conducted after the pandemic and using secondary materials, the paper sought to understand the social and material conditions in the forest and the coastal regions that shape this movement. Centring the waged relation of Adivasi workers opened the door to thinking about the marine fishing sector in India as a capitalist industry, while paying attention to social reproduction highlighted how the coastal and forest regions are spatially linked through their movement and labour. This highlights that the coasts and forests are going through distinct processes of capitalist intensification and expansion. Making connections between ecological appropriation, historical processes of resource extraction and marginalization, the paper finds that the extraction of fish resources in Goa is made productive through the hierarchization and differentiation of Adivasi workers. It reveals how the social relations of identity and caste mediate access to and define conditions of work at sea.

The Hybrid Recharge Delayed Oscillator: A More Realistic El Niño Conceptual Model

Abstract El Niño–Southern Oscillation (ENSO) is the leading mode of climate interannual variability, with large socioeconomical and environmental impacts, potentially increasing with climate change. Improving its understanding may shed further light on its predictability. Here we revisit the two main conceptual models for explaining ENSO cyclic nature, namely, the recharge oscillator (RO) and the advective–reflective delayed oscillator (DO). Some previous studies have argued that these two models capture similar physical processes. Yet, we show here that they actually capture two distinct roles of ocean wave dynamics in ENSO’s temperature tendency equation, using observations, reanalyses, and Climate Model Intercomparison Project (CMIP) models. The slow recharge/discharge process mostly influences central-eastern Pacific by favoring warmer equatorial undercurrent and equatorial upwelling, while the 6-month delayed advective–reflective feedback process dominates in the western-central Pacific. We thus propose a hybrid recharge delayed oscillator (RDO) that combines these two distinct processes into one conceptual model, more realistic than the RO or DO alone. The RDO eigenvalues (frequency and growth rate) are highly sensitive to the relative strengths of the recharge/discharge and delayed negative feedbacks, which have distinct dependencies to mean state. Combining these two feedbacks explains most of ENSO frequency diversity among models. Thanks to the two different spatial patterns involved, the RDO can even capture ENSO spatiotemporal diversity and complexity. We also develop a fully nonlinear and seasonal RDO, even more robust and realistic, investigating each nonlinear term. The great RDO sensitivity may explain the observed and simulated richness in ENSO’s characteristics and predictability. Significance Statement El Niño and La Niña events, and the related Southern Oscillation, cause the largest year-to-year variations of Earth’s climate. Yet the theories behind them are still debated, with two main conceptual models being the recharge oscillator and the delayed oscillator. Our purpose here is to address this debate by developing a more realistic theory, a hybrid recharge delayed oscillator. We show how simple yet realistic it is, with equivalent contributions from the slow recharge process and from the faster delayed feedback. It even captures the observed El Niño and La Niña diversity in space and in frequency. Future studies could use the simple theoretical framework provided here to investigate El Niño–Southern Oscillation (ENSO) in observations, theories, climate models diagnostics and forecasts, and global warming projections.

A comprehensive assessment of the economic and technical viability of a zero liquid discharge (ZLD) hybrid desalination system for water and salt recovery

Brine, a by-product of desalination and industrial facilities, is becoming more and more of an environmental issue. This comprehensive techno-economic assessment (TEA), focusing on the technical and economic aspects, investigates the performance and viability of a novel hybrid desalination brine treatment system known as zero liquid discharge (ZLD). Notably, this research represents the first instance of evaluating the feasibility and effectiveness of integrating three distinct desalination processes, namely brine concentrator (BC), high-pressure reverse osmosis (HPRO), and membrane-promoted crystallization (MPC), within a ZLD framework. The findings of this study demonstrate an exceptional water recovery rate of 97.04%, while the energy requirements stand at a reasonable level of 17.53 kWh/m3. Financially, the ZLD system proves to be at least 3.28 times more cost-effective than conventional evaporation ponds and offers comparable cost efficiency to alternatives such as land application and deep-well injection. Moreover, the ZLD system exhibits profitability potential by marketing both drinking water and solid salt or solely desalinated water. The daily profit from the sale of generated water varies from US$194.08 to US$281.41, with Greece and Cyprus attaining the lowest and highest profit, respectively. When considering the sale of both salt and water, the profit rises by 8% across all locations.

Dynamic simulation of immiscible displacement in fractured porous media

Investigating immiscible displacement in fractured porous media is essential for understanding the two-phase flow behavior within pores and fractures. In this work, a three-dimensional pore-fracture network model was developed to address the influence of fracture on flow patterns and to characterize fracture-matrix crossflow under different flow conditions. Sensitivity studies at a wide range of viscosity ratios and capillary numbers underscored that fracture significantly influenced flow patterns in the capillary fingering zone. Fracture with an advantageous path effect in the displacement direction caused a shift in the boundary of capillary fingering zone toward an increase in capillary numbers. As fracture aperture decreased and aspect ratio increased, there was a discernible decline in the crossflow rate. When fracture aperture equaled average matrix throat diameter, fracture lose advantageous path effect in compact displacement zone but retained it in viscous fingering and capillary fingering zones. Distinct matrix-fracture crossflow development processes were observed in different zones: in cross zone, following displacement breakthrough, the crossflow underwent a “long-term” process to attain stability. Viscous fingering zone promptly achieved stability post-breakthrough, whereas both capillary fingering and compact displacement zones had already reached a stable state before breakthrough. Nonlinear variations in breakthrough saturation were observed in the cross zone between compact displacement and capillary fingering zones. The control process of immiscible displacement exhibited variability under different flow conditions: compact displacement zone was characterized by matrix dominance, viscous fingering zone was jointly controlled by matrix displacement and fracture-matrix crossflow, and capillary fingering zone was primarily governed by fracture-matrix crossflow. These findings enhance scholarly comprehension of immiscible displacement behavior in fractured porous media.

Органические продукты питания: медико-социальный аспект.

The article presents current information on trends in the consumption of organic food products in the world, information from foreign studies on their impact on public health. The market for these food products has grown significantly since the late 20th century and today represents a multi-billion dollar industry with distinct production, processing, distribution and retail systems. The relevance of studying the prevalence of consumption of organic food products among the population of various countries is increasing due to the increase in the modern world of demand and motivation among social groups of the population, especially among adherents of a healthy lifestyle. The purpose of the study is to review and analyze modern scientific foreign literature on the development of the organic food market from the standpoint of health conservation and medical and social perspectives. As a result of the review, it was revealed that the understanding currently clearly manifested in various social circles of the need to improve the level of quality of health of the individual and the population as a whole, the demand for the production of safe, micronutrient-rich, healthy food products, especially products of plant origin, actualize the expansion of production organic food products. In many countries around the world, there is an increase in consumer demand for organic food products; their regular consumers are people, mainly women, who care about their health, are physically active, have a higher level of education and income, and live mainly in high-income countries. The certain high cost of organic food products, depending on labor-intensive production methods and certification costs, often leads to unequal access to organic food products. The positive impact of organic foods on health status and the risk of developing chronic diseases is associated with a higher content of biologically active compounds and a lower content of substances harmful to health. Overall, large intervention and population-based studies are needed on the health effects of organic foods, comparing the quality, safety, bioactive compounds, nutritional and phytochemical value of foods in conventional and organic production systems using new research methods.

Friction Welding Processes: A Review

Friction welding is a sort of solid-state welding process that does not use flux, shielding gases, or filler metal; instead, the heat needed to fuse the materials is produced by the friction between two or more objects moving relative to one another. This kind of welding is an alternative to the traditional fusion and adhesive-based welding procedures. The method is reliable, capable of joining materials that would seem hard to join with traditional welding, and suitable for joining both similar and dissimilar materials including wood, steel, aluminum, copper, masurium, nickel, zinc and carbon steel. Friction welding can be carried out by using several techniques including linear, rotary, friction stir, direct drive and inertia welding. Each of these welding techniques is distinct and are named according to the relative motion involved. Although the process varies slightly subject to the type of motion, the procedure is consistent and the resultant joint is comparable with those obtained through conventional welding technique. This study reviews the distinct friction welding processes and specific techniques involved in the process.

Assessment of spermatogenesis in camels via seminiferous tubule staging and testosterone profiling

Objective: To investigate the successive morphological stages of spermatogenesis, hormonal regulation, and testosterone profile in dromedary camel reproduction. Methods: Testicular tissue samples were obtained from 12 dromedary bull camels aged 7 to 8 at a local abattoir. The histological assessment involved tissue processing, hematoxylin and eosin (H &amp; E) staining, and examination under a microscope. Stereological analysis, germ cell identification, and assessment of seminiferous tubules and maturation were conducted. Testosterone assay was performed by radioimmunoassay using blood samples collected at regular intervals. Results: The study revealed 12 phases of the dromedary camel's seminiferous epithelium cycle, highlighting distinct morphological characteristics and cellular processes. Acrosomal migration, maturation, cap formation, and the Golgi-mediated synthesis of proacrosomal vesicles were also explained in dimension, as were the steps of acrosome biogenesis. Spermatids and mature sperm cells were present when spermatogenesis phases were examined. An analysis of the dimensions of seminiferous tubules revealed specific measures for diameter, area, and epithelial height about luminal characteristics. Moreover, there were noticeable variations in the serum testosterone concentrations during the study period, indicating temporal dynamics. Conclusions: This study outlines the spermatogenesis process in dromedary camels across 12 stages, emphasizing cellular dynamics and acrosomal biogenesis. It also provides seminiferous tubule measurements and observes seasonal testosterone fluctuations, offering insights into reproductive regulation and potential strategies for camel breeding conservation.

Podocytopathy and Nephrotic Syndrome in Smpdl3b Gene Knockout Mice

Recent clinical studies have shown that downregulation of sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) in podocytes is a hallmark of idiopathic nephrotic syndrome in children. Meanwhile, there is increasing evidence suggesting that changes of SMPDL3b level in podocytes determine the phenotypes of podocyte injury in glomerular diseases. However, it remains unknown whether SMPDL3b exclusively plays a crucial role in the pathogenesis of podocytopathy and nephrotic syndrome without any other pathogenic stimuli. In the present study, we tested whether Smpdl3b gene knockout induces podocyte injury and nephrotic syndrome in mice. By immunohistochemistry and confocal microscopy, we first confirmed that SMPDL3b was highly expressed in podocytes of wild type (WT) mice but undetectable in these cells of Smpdl3b knockout (KO) mice. Also, Western blot analysis showed that SMPDL3b was not detected in podocytes isolated from Smpdl3b KO mice compared to podocytes of WT mice. Although no significant morphologic changes in glomeruli were observed in Smpdl3b KO mice under light microscope, severe proteinuria and albuminuria were found in Smpdl3b KO mice compared to control littermates. Transmission electron microscopy showed that podocytes of Smpdl3b KO mice had distinctive foot process effacement and moderate microvillus formation and vacuolation. These functional and morphologic changes indicate the development of nephrotic syndrome in mice lacking Smpdl3b gene. In vitro, Smpdl3b gene silencing induced remarkable decrease in podocin levels in podocytes compared to control cells. Phalloidin staining of F-actin showed elevation of cortical actin and reduction of stress fiber in podocytes transfected with Smpdl3b shRNA. Such actin cytoskeleton rearrangement induced by Smpdl3b gene silencing was significantly attenuated by choline but exaggerated by CDP-choline, which are product and substrate of SMPDL3b, respectively. Furthermore, atom force microscopy was used to study mechanical properties of podocytes lacking Smpdl3b gene as the outcome of actin cytoskeleton reorganization. Smpdl3b gene deletion was found to increase podocyte height but decrease cortical elasticity in these cells. Moreover, these pathological changes were markedly inhibited by choline. Taken together, our findings suggest that SMPDL3b is essential for the maintenance of functional and structural integrity of podocytes and that Smpdl3b gene knockout may induce podocytopathy and nephrotic syndrome in mice. This study was supported by NIH grants DK054927 and DK120491. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

224. Distinct Process of Rumination and Worry in Repetitive Negative Thinking

224. Distinct Process of Rumination and Worry in Repetitive Negative Thinking

Recent Advances in Catalytic Compounds Developed by Thermal Treatment of (Zr-Based) Metal–Organic Frameworks

Metal–organic frameworks (MOFs) have been the subject of extensive scientific investigation in the last three decades and, currently, they make up one of the types of compounds most studied for their potential application in a wide range of distinct catalytic processes. Pristine MOF compounds provide several intriguing benefits for catalytic applications, including large interior surface areas and high densities of active sites; high catalytic reaction rates per volume; post-synthesis modifications with complementary catalytic groups; and the ability for multiple functional groups to catalyze the reaction. For most large-scale catalytic applications, including those in fuel processing, gas emission reduction, and chemical synthesis, pristine MOFs often show limited stabilities and opportunities for regeneration at high temperatures. As a result, the real applications of MOFs in these technologies are likely to be constrained, and a controlled thermal modification to prepare MOF-derivative compounds has been applied to induce crystalline structural changes and increase the structural stability of the MOFs, enhancing their potential applicability in more severe catalytic processes. Recent advances concerning the use of this strategy to boost the catalytic potential of MOF-derivative compounds, particularly for stable Zr-based MOFs, are outlined in this short review article.

Relearning and remembering: A gradualist account

Relearning and remembering are usually seen as two distinct cognitive processes in contemporary philosophy of memory. In particular, relearning is sometimes regarded as a kind of memory error. This paper aims to address two questions. First, is relearning a kind of memory error? Second, how to draw a distinction (if any) properly between relearning and remembering? My answer to the first question is a conditional ‘yes’—it depends on whether relearning can be falsidical and whether metacognitive monitoring counts as a part of memory process. My answer to the second question appeals to a gradualist account, according to which the distinction between relearning and remembering is not an absolute yes-or-no affair, but a matter of degrees.

Examining processes of change for acceptance and commitment therapy and cognitive behavioral therapy self-help books with depressed college students

ABSTRACT Given the prevalence of depression, it is worthwhile to consider a variety of treatment approaches to reach as many sufferers as possible, including highly accessible formats such as self-help books. Books based in acceptance and commitment therapy (ACT) and cognitive behavioral therapy (CBT) propose to treat depression through distinct processes of change, though the degree to which these treatments are distinguishable in this format is unclear. Furthermore, it is possible that some individuals may respond better to therapeutic processes from one approach over the other based on personal preferences. We tested the effects of ACT and CBT self-help books on processes of change in a sample of 139 depressed college students in which some participants were given a choice of treatment and others were randomized. Cognitive fusion, which improved better in the ACT group, was the only process of change that distinguished the two treatments. Additionally, early improvements in cognitive fusion were associated with less depression-related stigma at posttreatment. Lastly, randomization, instead of choosing a treatment, led to greater improvements in almost all processes of change. We discuss how these findings inform personalized care, tangible differences between ACT and CBT, and effective practices for treating depression at large scale.