Analysis Of Activity Research Articles

Electromyographic Analysis of Large Muscle Activity in Progressive Collapsing Foot Deformity.

There are various deformities described in the spectrum of Progressive Collapsing Foot Deformity (PCFD) which not only have adverse effects on the foot but also on the entire lower limb. Early lower limb muscular fatigue and pain during exertion is the most common complaint of patients with PCFD. Surface electromyography (sEMG) provides an accurate assessment of muscle activity. In this study, we aim to compare the activities of quadriceps, hamstrings, and gastrosoleus muscle groups of adult patients with PCFD with normal lower limbs and correlate the radiological parameters and functional effects of PCFD with the activities. Thirty patients with bilateral PCFD and 30 controls underwent weight-bearing anteroposterior (AP), lateral, and hindfoot alignment radiographs of the foot. Radiographic parameters of PCFD were assessed. Surface electromyography was used to assess the quadriceps, hamstrings, and gastrosoleus activities, and this was compared between the 2 groups and correlated with radiological measurements of PCFD. Tegner activity questionnaire was used to assess the functional effects of collapsed arch. Electrical activities of all muscle groups were significantly higher in cases than controls. Meary's angle and hindfoot moment arm had significant correlations with hamstring activity (P = .013) and gastrosoleus activity (P = .027), respectively. Tegner scores of cases were significantly lower than those of controls (P = .041). The PCFD causes an increase in activity of large muscles of the affected lower limb which act on joints other than those in the foot. This finding may be due to several compensatory mechanisms that counteract the deforming forces. This may be a cause for the frequent complaint, early fatigue, and hence functional impairment. However, most radiological parameters did not correlate with muscle activities and larger study size may be required for further association. Diagnostic: Level 3.

Development and characterization of innovative bio-based edible films supplemented with cell-free supernatant and whole-cell postbiotic of Lactobacillus gasseri

More recently, the concepts of cell-free supernatants (CFS, so-called postbiotics) and whole-cell postbiotics (WCP) of probiotics have gained increasing attention for the development of bio-based films. However, reports on CFS and WCP of Lactobacillus gasseri remain scarce. In this study, pea protein isolate/psyllium mucilage was incorporated with CFS and WCP of L. gasseri to produce bio-based edible films. pH, total soluble solid content, antioxidant activity, total phenolic content, antimicrobial activity, and structural analyses were conducted to characterize the CFS and WCP of L. gasseri. Furthermore, the effects of CFS (10% and 20%, v/v) and WCP (10% and 20%, v/v) on the physicochemical, mechanical, barrier, optical, microstructural, and antimicrobial properties of the bio-based films were investigated. The results showed that CFS and WCP exhibited antioxidant and antibacterial activities and were significant sources of phenolic compounds. The incorporation of 20% WCP caused a significant increase in the thickness and water vapor permeability of films, while a significant increase in moisture content was observed with 10% WCP. The control and 10% WCP films had the highest tensile strength values. Furthermore, the addition of 10% WCP resulted in a significant increase in elasticity. Films incorporating CFS and WCP exhibited lower opacity values and darker, yellow, and red color intensities. The addition of CFS and WCP caused a rough texture and cracked structure on the surface of the film. In conclusion, pea protein/psyllium mucilage-based films containing CFS and WCP of L. gasseri can be considered as a new alternative for environmentally friendly bio-based films.

Improvement and application of vacuum-infiltration system in tomato.

The Agrobacterium-mediated transient expression system has been developed and applied to various plants as an alternative to stable transformation. However, its application in tomatoes is still limited due to low expression efficiency. In this study, we describe an improved vacuum-infiltration system that can be used in both tomato fruits and leaves. Notably, this study is the first report of vacuum infiltration in attached tomato fruits. The feasibility of the improved vacuum-infiltration system in Micro-Tom tomato was confirmed by various assays, including multiple fluorescent protein expression analysis, β-glucuronidase activity analysis, and RUBY reporter visualization. Subsequently, the improved vacuum-infiltration system was successfully applied to tomato biotechnology research. Herein, a trichome-specific promoter in tomato was identified that can drive the directional synthesis of specific plant natural products (PNPs). Additionally, based on the assessment results of the improved vacuum-infiltration system, we obtained a flavonoid-rich tomato variety through the stable transformation of AmRosea and AmDelila. In a significant practical application, we successfully synthesized the high-value scutellarin in tomato, which provides an alternative route for the production of PNPs from plants. In addition, the improved vacuum-infiltration system has been demonstrated to be suitable for commercial tomato varieties ('Emerald' and 'Provence') as well. The improved vacuum-infiltration system not only speeds up fundamental and applied research in tomato but also offers an additional powerful tool for advancing tomato synthetic biology research.

Microsyringe-assisted visual volume detection based on phase separation: the case of chymosin milk-clotting activity study.

The constantly diverse demand scenarios for rapid on-site analysis have put forward high requirements for developing low-cost and user-friendly visual detection methods. Therefore, developing a visual detection method with simple operation and intuitive results has important practical value in the field of analysis and detection, but it is also challenging. In this work, we propose a microsyringe-assisted visual volume detection method based on phase separation, and apply it to analyze the milk-clotting activity of chymosin. Chymosin can cause phase separation of milk with whey in the mobile phase and curd in the gel state. The network structures of casein in curd can trap water molecules, resulting in separation of whey from curd gradually. Therefore, the analysis of chymosin milk-clotting activity can be realized according to the volume of whey measured using a portable microsyringe. This method shows a good linear correlation when the concentration of chymosin ranges from 1.02 U L-1 to 1020 U L-1 and the limit of detection of this method for chymosin is calculated to be 0.03 U mL-1. This work successfully realizes the visual analysis of chymosin milk-clotting activity based on the enzyme-triggered phase separation. It also shows great promise to be applied in other phase separation-based detection systems with the advantages of high accuracy, great portability and user-friendliness.

Exploring the genomic traits of infant-associated microbiota members from a Zimbabwean cohort

IntroductionOur understanding of particular gut microbiota members such as Bifidobacterium and Enterococcus in low-middle-income countries remains very limited, particularly early life strain-level beneficial traits. This study addresses this gap by exploring a collection of bacterial strains isolated from the gut of Zimbabwean infants; comparing their genomic characteristics with strains isolated from infants across North America, Europe, and other regions of Africa.Materials and methodFrom 110 infant stool samples collected in Harare, Zimbabwe, 20 randomly selected samples were used to isolate dominant early-life gut microbiota members Bifidobacterium and Enterococcus. Isolated strains were subjected to whole genome sequencing and bioinformatics analysis including functional annotation of carbohydrates, human milk oligosaccharide (HMO) and protein degradation genes and clusters, and the presence of antibiotic resistance genes (ARGs).ResultsThe study observed some location-based clustering within the main five identified taxonomic groups. Furthermore, there were varying and overall species-specific numbers of genes belonging to different GH families encoded within the analysed dataset. Additionally, distinct strain- and species-specific variances were identified in the potential of Bifidobacterium for metabolizing HMOs. Analysis of putative protease activity indicated a consistent presence of gamma-glutamyl hydrolases in Bifidobacterium, while Enterococcus genomes exhibited a high abundance of aspartyl peptidases. Both genera harboured resistance genes against multiple classes of antimicrobial drugs, with Enterococcus genomes containing a higher number of ARGs compared to Bifidobacterium, on average.ConclusionThis study identified promising probiotic strains within Zimbabwean isolates, offering the potential for early-life diet and microbial therapies. However, the presence of antibiotic resistance genes in infant-associated microbes raises concerns for infection risk and next-stage probiotic development. Further investigation in larger cohorts, particularly in regions with limited existing data on antibiotic and probiotic use, is crucial to validate these initial insights.Impact statementThis research represents the first investigation of its kind in the Zimbabwean context, focusing on potential probiotic strains within the early-life gut microbiota. By identifying local probiotic strains, this research can contribute to the development of probiotic interventions that are tailored to the Zimbabwean population, which can help address local health challenges and promote better health outcomes for infants. Another essential aspect of the study is the investigation of antimicrobial resistance genes present in Zimbabwean bacterial strains. Antimicrobial resistance is a significant global health concern, and understanding the prevalence and distribution of resistance genes in different regions can help inform public health policies and interventions.

Single-particle rotational sensing for analyzing the neutralization activity of antiviral antibodies

Due to the pathogen-specific targeting, neutralization capabilities, and enduring efficacy, neutralizing antibodies (NAs) have received widespread attentions as a critical immunotherapeutic strategy against infectious viruses. However, because of the high variability and complexity of pathogens, rapid determination of neutralization activity of antiviral antibodies remains a challenge. Here, we report a new method, named as out-of-plane polarization imaging based single-particle rotational sensing, for rapid analysis of neutralization activity of antiviral antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the spike protein functionalized gold nanorods (AuNRs) and angiotensin-converting enzyme 2 (ACE2) coated gold nanoparticles (AuNPs) as the rotational sensors and chaperone probes, we demonstrated the single-particle rotational sensing strategy for the measurement of rotational diffusion coefficient of the chaperone-bound rotational sensors caused by the specific spike protein-ACE2 interactions. This enables us to measure the neutralizing activity of neutralizing antibody from the analysis of dose-dependent changes in rotational diffusion coefficient (Dr) of the rotational sensors upon the treatment of SARS-CoV-2 antibody. With this technique, we achieved the quantitative determination of neutralization activity of a commercially available SARS-CoV-2 antibody (IC50, 294.1 ng/mL) with satisfying accuracy and anti-interference ability. This simple and robust method holds the potential for rapid and accurate evaluation of neutralization activity against different pathogenic viruses.

Differential Impact of Serotonin Signaling Methylphenidate on Young versus Adult: Insights from Behavioral and Dorsal Raphe Nucleus Neuronal Recordings from Freely Behaving Rats.

Methylphenidate (MPD) remains a cornerstone pharmacological intervention for managing ADHD, yet its increasing usage among ordinary youth and adults outside clinical contexts necessitates a thorough investigation into its developmental effects. This study seeks to simultaneously investigate the behavioral and neuronal changes within the dorsal raphe (DR) nucleus, a center of serotonergic neurons in the mammalian brain, before and after the administration of varying doses of acute and chronic MPD in freely behaving young and adult rats implanted with DR recording electrodes. Wireless neuronal and behavioral recording systems were used over 10 consecutive experimental days. Eight groups were examined: saline, 0.6, 2.5, and 10.0 mg/kg MPD for both young and adult rats. Six daily MPD injections were administered on experimental days 1 to 6, followed by a three-day washout period and MPD re-administration on experimental day 10 (ED10). The analysis of neuronal activity recorded from 504 DR neurons (DRNs) in young rats and 356 DRNs in adult rats reveals significant age-dependent differences in acute and chronic MPD responses. This study emphasizes the importance of aligning electrophysiological evaluations with behavioral outcomes following extended MPD exposure, elucidating the critical role of DRNs and serotonin signaling in modulating MPD responses and delineating age-specific variations in young versus adult rat models.

Antidiabetic Activity and Pancreatic Histopathology Analysis of Averrhoa bilimbi L. Leaves Extract on Alloxan-Induced Diabetes on Wistar Mice

Background: Diabetes mellitus is a multi-etiological metabolic disorder characterized by chronic hyperglycemia, total or relative insulin deficiency, and further complications by metabolic disorders. Drug therapy for diabetes mellitus is costly and fraught with potential side effects. The aim of this research is to investigate antidiabetic and histopathological analysis of ethanolic A. bilimbi leaves extract in alloxan induced diabetic mice.Methods: Wuluh starfruit leaves is one of Indonesia's plants that can be used to treat diabetes mellitus. Thirty male Wistar mice were divided into five groups as follows: Negative control group that didn't receive any treatment, Diabetes control group that received alloxan 150 mg/kg, Positive control group that received glibenclamide 600 μg/kg, and lastly the two test groups that received A. bilimbi leaves extract 150 and 300 mg/kg orally for 14 days. After extract administration, blood glucose and histopathological alterations in the pancreas of diabetic mice were observed.Results: Alloxan to the diabetes control group significantly raised blood glucose levels compared to the negative control group. Administration of wuluh starfruit leaves extract and glibenclamide could significantly lower blood sugar levels compared to the diabetic control group. Administration of wuluh starfruit leaves extract treatment and glibenclamide also showed favorable effect on the histopathological changes of the pancreas in alloxan induced diabetes.Conclusion: The study concludes the administration of wuluh starfruit leaves extract (150 and 300 mg/kg) and glibenclamide could reduce blood glucose levels and can help with cell regeneration and protecting pancreatic cells from damage caused by alloxan.Keywords: A. bilimbi leaves extract; Alloxan; Diabetes; Pancreatic histopathology

Arecoline inhibits the growth of Spodoptera litura by inducing intestinal metabolic dysfunction

Arecoline (ACL), an active constituent derived from Areca catechu L., exerts various pharmacological effects and serves as a potential plant-based insecticide. However, the effects of ACL on Spodoptera litura, an important and widely distributed agricultural pest, remain unknown. This study aimed to elucidate the mechanism underlying ACL-induced toxicity and its inhibitory effects on larval growth and development through intestinal pathology observations, intestinal transcriptome sequencing, intestinal digestive enzyme activity analysis. The results indicated that ACL exposure leads to pathological alterations in the S. litura midgut. Furthermore, the detection of digestive enzyme activity revealed that ACL inhibits the activities of acetyl CoA carboxylase, lipase, α-amylase, and trypsin. Simultaneously, upregulation of superoxide dismutase activity and downregulation of malondialdehyde levels were observed after ACL exposure. Transcriptome analysis identified 1118 genes that were significantly differentially expressed in the midgut after ACL exposure, potentially related to ACL toxic effects. Notably, ACL treatment downregulated key enzymes involved in lipid metabolism, such as fatty acid binding protein 2-like, pancreatic triacylglycerol lipase-like, pancreatic lipid-related protein 2-like, and fatty acid binding protein 1-like. Taken together, these results suggest that ACL induces midgut damage and impedes larval growth by suppressing digestive enzyme activity in the intestine. These findings can aid in the development of environmentally friendly plant-derived insecticides, utilizing ACL to effectively combat S. litura proliferation.

Correction to: The AI community building the future? A quantitative analysis of development activity on Hugging Face Hub

Correction to: The AI community building the future? A quantitative analysis of development activity on Hugging Face Hub

Educational policy in times of war 2022: A case study of the Twitter of the Ministry of Education and Science in Poland

The aim of the conducted research was to analyze the activity of the Polish Ministry of Education and Science on Twitter and to diagnose and then describe the perspective (experiences, reflections, postulates) of Twitter users, thus enabling the analysis and evaluation of activities undertaken in the field of shaping education policy in times of Russian aggression to Ukraine. The subject of the research were entries and comments posted on the Twitter platform on the account of the Polish Ministry of Education and Science in Poland placed in the time period from February 24, 2022 (the first day of Russia’s invasion of Ukraine) to June 1, 2022 (celebration related to Children’s Day). The collected data were analyzed in the MAXQDA program in accordance with the prepared – described in detail in the article – code key. As part of the research, a total of 259 posts and 2,339 comments were analyzed. It turned out that Twitter users are reluctant to create recommendations (3% of all entries), while the vast majority of comments contain negative opinions and experiences related to education policy. The analysis also showed a worrying trend towards an increasing number of hate speech comments. Users often used the Twitter platform to mock politicians, but also made statements directed against the Ukrainian people. Based on the conducted research, it is extremely difficult to describe the activities undertaken in the field of education policy by the Polish Ministry of Education and Science. It should be noted that the analyzed entries in most cases are only very short messages, often referring only to visits or speeches by politicians. At the same time, it is worth emphasizing that comments posted by users rarely enter into substantive polemics, because they are usually only a vent for very negative emotions.

Structural Basis for Methine Excision by a Heme Oxygenase-like Enzyme.

Heme oxygenase-like domain-containing oxidases (HDOs) are a rapidly expanding enzyme family that typically use dinuclear metal cofactors instead of heme. FlcD, an HDO from the opportunistic pathogen Pseudomonas aeruginosa, catalyzes the excision of an oxime carbon in the biosynthesis of the copper-containing antibiotic fluopsin C. We show that FlcD is a dioxygenase that catalyzes a four-electron oxidation. Crystal structures of FlcD reveal a mononuclear iron in the active site, which is coordinated by two histidines, one glutamate, and the oxime of the substrate. Enzyme activity, Mössbauer spectroscopy, and electron paramagnetic resonance spectroscopy analyses support the usage of a mononuclear iron cofactor. This cofactor resembles that of mononuclear non-heme iron-dependent enzymes and breaks the paradigm of dinuclear HDO cofactors. This study begins to illuminate the catalytic mechanism of methine excision and indicates convergent evolution of different lineages of mononuclear iron-dependent enzymes.

Phytochemical Analysis and Antioxidant Activity of Pandila Tree Leaves (Saurauia Tristlyla Dc) From Tibo Village

Introduction: The Pandila tree known as pandila (Saurauia tristlyla DC) is one of the plants that has been traditionally used as a medicinal material. Pandila has been traditionally used by the community as a medicine for external and internal diseases, for example, pandila leaves are believed by the Tibo Village community to absorb congealed blood due to accidents. This study aims to determine the secondary metabolite content and antioxidant activity of pandila leaves. Method: The research method used in this study is a descriptive method by looking at changes in color and liquid form in alkaloids, Flavonoid, Tannin, Saponin, Steroid, Terpenoid, and Carotenoid compounds. Phytochemical analysis was carried out on 96% ethanol extract of pandila leaves. The DPPH method was used to determine the antioxidant activity. The results of phytochemical analysis obtained on the leaves of Pandila tree leaves (Saurauia Tristlyla DC) using 96% ethanol solvent are old leaf extracts and young leaves of pandila positively contain 3 compounds namely Tannins, Steroids, and Carotenoids. Results and Discussion: The results of the antioxidant activity test of Pandila leaf extract using the DPPH method on old leaves have an IC50 of 101, 2844 ppm including in the moderate category, and on young leaves have an IC50 of 76.688 ppm which is included in the strong category. Conclusion: Pandila tree leaves are still safe to be used as traditional medicine, by looking at the tannin, steroid, and carotenoid compounds contained in pandila leaves. In addition, the results of antioxidant activity analysis are also a supporting factor where the antioxidant content in old leaves and young leaves of Pandila trees is classified as strong and moderate, so this plant is still safe to be used as a traditional medicinal plant.

ALTMAN: A Novel Method for Cell Cycle Analysis.

Accurate analysis of S-phase fraction is crucial for the assessment of cell proliferation levels, tumor malignancy and prognostic effects of treatment. Most of the currently developed methods for S-phase cell analysis rely on flow cytometric analysis of DNA content determination. However, the lack of standardized procedures for sample analysis and interpretation of cell cycle fitting graphs poses a significant limitation in clinical practice for utilizing flow cytometry to measure the cell cycle based on DNA content. Herein, we developed an approach for analyzing S-phase cells based on telomerase activity determination. Briefly, this approach distinguishes S-phase cells in cell populations via direct fluorescence tracking of telomerase activity within individual cells. The dynamic analysis of telomerase activity in different cell cycles was made possible by the ALTMAN strategy developed in our previous studies, which has been successfully employed to distinguish S-phase cells in cultured cells. This method offers a novel avenue for the assessment of cell cycle status and the evaluation of the proliferation status of tumor cells and the prognosis effect of tumor patients via analyzing the differences in telomerase activity during different cell cycle processes.

Distributions, interactions, and dynamics of prokaryotes and phages in a hybrid biological wastewater treatment system

BackgroundUnderstanding the interactions and dynamics of microbiotas within biological wastewater treatment systems is essential for ensuring their stability and long-term sustainability. In this study, we developed a systematic framework employing multi-omics and Hi-C sequencing to extensively investigate prokaryotic and phage communities within a hybrid biofilm and activated sludge system.ResultsWe uncovered distinct distribution patterns, metabolic capabilities, and activities of functional prokaryotes through the analysis of 454 reconstructed prokaryotic genomes. Additionally, we reconstructed a phage catalog comprising 18,645 viral operational taxonomic units (vOTUs) with high length and contiguity using hybrid assembly, and a distinct distribution of phages was depicted between activated sludge (AS) and biofilm. Importantly, 1340 host-phage pairs were established using Hi-C and conventional in silico methods, unveiling the host-determined phage prevalence. The majority of predicted hosts were found to be involved in various crucial metabolic processes, highlighting the potential vital roles of phages in influencing substance metabolism within this system. Moreover, auxiliary metabolic genes (AMGs) related to various categories (e.g., carbohydrate degradation, sulfur metabolism, transporter) were predicted. Subsequent activity analysis emphasized their potential ability to mediate host metabolism during infection. We also profiled the temporal dynamics of phages and their associated hosts using 13-month time-series metagenomic data, further demonstrating their tight interactions. Notably, we observed lineage-specific infection patterns, such as potentially host abundance- or phage/host ratio-driven phage population changes.ConclusionsThe insights gained from this research contribute to the growing body of knowledge surrounding interactions and dynamics of host-phage and pave the way for further exploration and potential applications in the field of microbial ecology.7mTZubWt51_LqpKWPutADaVideo

Pan-cancer analyses reveal the molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target.

The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.

Synthesis, characterization, and mechanistic insights into the enhanced anti-inflammatory activity of baicalin butyl ester via the PI3K-AKT pathway.

To investigate the anti-inflammatory activity and mechanism of Baicalin derivative (Baicalin butyl ester, BE). BE was synthesized and identified using UV-Vis spectroscopy, FT-IR spectroscopy, mass spectrometry (MS) and high-performance liquid chromatography (HPLC) methods. Its anti-inflammatory potential was explored by an in vitro inflammation model. Network pharmacology was employed to predict the anti-inflammatory targets of BE, construct protein-protein interaction (PPI) networks, and analysis topological features and KEGG pathway enrichment. Additionally, molecular docking was conducted to evaluate the binding affinity between BE and its core targets. qRT-PCR analysis was conducted to validate the network pharmacology results. The organizational efficiency was further evaluated through octanol-water partition coefficient and transmembrane activity analysis. UV-Vis, FT-IR, MS, and HPLC analyses confirmed the successfully synthesis of BE with a high purity of 93.75%. In vitro anti-inflammatory research showed that BE could more effectively suppress the expression of NO, COX-2, IL-6, IL-1β, and iNOS. Network pharmacology and in vitro experiments validated that BE's anti-inflammatory effects was mediated through the suppression of SRC, HSP90AA1, PIK3CA, JAK2, AKT1, and NF-κB via PI3K-AKT pathway. Molecular docking results revealed that the binding affinities of BA to the core targets were lower than those of BE. The Log p-value of BE (1.7) was markedly higher than that of BA (-0.5). Furthermore, BE accumulated in cells at a level approximately 200 times greater than BA. BE exhibits stronger anti-inflammatory activity relative to BA, possibly attributed to its better lipid solubility and cellular penetration capabilities. The anti-inflammatory mechanism of BE may be mediated through the PI3K-AKT pathway.

In vitro analysis of postbiotic antimicrobial activity against Candida Species in a minimal synthetic model simulating the gut mycobiota in obesity

Gut fungal imbalances, particularly increased Candida spp., are linked to obesity. This study explored the potential of Lactiplantibacillus plantarum cell-free extracts (postbiotics) to modulate the growth of Candida albicans and Candida kefyr, key members of the gut mycobiota. A minimal synthetic gut model was employed to evaluate the effects of Lactiplantibacillus plantarum postbiotics on fungal growth in mono- and mixed cultures. Microreactors were employed for culturing, fungal growth was quantified using CFU counting, and regression analysis was used to evaluate the effects of postbiotics on fungal growth. Postbiotics at a concentration of 12.5% significantly reduced the growth of both Candida species. At 24 h, both C. albicans and C. kefyr in monocultures exhibited a decrease in growth of 0.11 log CFU/mL. In contrast, mixed cultures showed a more pronounced antifungal effect, with C. albicans and C. kefyr reductions of 0.62 log CFU/mL and 0.64 log CFU/mL, respectively. Regression analysis using the Gompertz model supported the antifungal activity of postbiotics and revealed species-specific differences in growth parameters. These findings suggest that L. plantarum postbiotics have the potential to modulate the gut mycobiota by reducing Candida growth, potentially offering a therapeutic approach for combating fungal overgrowth associated with obesity.

Alzheimer's disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling.

Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer's disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases. We hypothesized that the reported increases in Aβ42, particularly in the endolysosomal compartment, promote the establishment of a product feedback inhibitory mechanism on γ-secretases, and thereby impair downstream signaling events. We conducted kinetic analyses of γ-secretase activity in cell-free systems in the presence of Aβ, as well as cell-based and ex vivo assays in neuronal cell lines, neurons, and brain synaptosomes to assess the impact of Aβ on γ-secretases. We show that human Aβ42 peptides, but neither murine Aβ42 nor human Aβ17-42 (p3), inhibit γ-secretases and trigger accumulation of unprocessed substrates in neurons, including C-terminal fragments (CTFs) of APP, p75, and pan-cadherin. Moreover, Aβ42 treatment dysregulated cellular homeostasis, as shown by the induction of p75-dependent neuronal death in two distinct cellular systems. Our findings raise the possibility that pathological elevations in Aβ42 contribute to cellular toxicity via the γ-secretase inhibition, and provide a novel conceptual framework to address Aβ toxicity in the context of γ-secretase-dependent homeostatic signaling.

Analysis of Supraglottic Activity during Vocalization in Flamenco Singers.

Flamenco is a traditional music originally from Andalusia in southern Spain. Some of the vocal resources used in Flamenco have components of voice distortion and other voice qualities that could sound like hyperfunctional voice productions. The present study aimed at observing supraglottic activity in flamenco singers while engaged in singing at various degrees of pitch and loudness and while engaged in realizing phonatory tasks. A total of eighteen flamenco singers with at least 5 years of voice training were recruited. Flexible endoscopic voice evaluations were recorded and edited to provide samples of different pitches, loudness levels, and phonatory tasks. Sound was removed from video samples. Two blinded laryngologists were asked to assess antero-posterior compression, medial compression, pharyngeal compression, and VLP for every sample, using a visual analog scale. Significantly higher values were found for medial compression, anterior-posterior compression, VLP and pharyngeal compression during high loudness levels when compared to medium and low loudness. Overall, medial compression was lower than anterior-posterior compression. Supraglottic activity is present in flamenco singing in the four laryngoscopic variables. It seems to be that supraglottic activity increases with loudness level and pitch. This behavior could be a natural and necessary aspect of flamenco singing present during both sustained vowels and song.