Swelling granular media can experience size-induced percolation phenomena giving rise to segregation. In this work, the Discrete Element Method is employed to investigate the effects of size ratio and swelling kinetics on the segregation. The numerical analysis was carried out on a binary mixture consisting of coarse and fine particles and several mixing indices found in literature were adapted and tested for evaluating the mixing of expanding systems. Additionally, a relative percolation velocity was employed to quantify the percolation of fine particles. The results show that the percolation of fine particles becomes more significant as the size ratio increases. Additionally, results showed that the swelling kinetics has no impact on the segregation tendency. This research provides valuable insight into the effect of size ratio and swelling kinetics on the segregation behaviour of swelling granular materials, which can contribute to understanding percolation phenomena in various fields.
The capacity to form biofilms is a common trait among many microorganisms present on Earth. In this study, we demonstrate for the first time that the fatal pine pitch canker agent, Fusarium circinatum, can lead a biofilm-like lifestyle with aggregated hyphal bundles wrapped in extracellular matrix (ECM). Our study suggests that F. circinatum biofilms respond to a changing environment, demonstrated by poor and optimal biofilm development under particular abiotic conditions, including temperature and pH. Further analysis revealed that while planktonic cells produced small amounts of ECM per unit of the biomass, heat- and azole-exposed biofilms produced significantly more ECM than non-exposed biofilms. The increased synthesis of ECM in biofilms due to these abiotic factors underscores biofilm importance in response to various stress conditions, demonstrating the adaptability of F. circinatum to changing environments. Interestingly, azole exposure also led to biofilms that were resistant to DNase, which typically uncouples biofilms by penetrating the biofilm and degrading its extracellular DNA; we propose that DNases were likely hindered from reaching target cells by the ECM barricade. The interplay between antifungal treatment and DNase enzyme suggests a complex relationship between eDNA, ECM, and antifungal agents in F. circinatum biofilms. Therefore, our results show how a phytopathogen’s sessile (biofilm) lifestyle could influence its response to the surrounding environment.
A Rare Case: IgG4-Related Chronic Inflammatory Disease with Kidney InvolvementFatos METE¹, Tuba MENGENECI¹, Emre ALBAYRAK¹, Yavuz AYAR2, Melike NALBANT3, Ilknur MUTLUCAN4, Zeliha Fusun BABA51Bursa City Hospital, Department of Internal Medicine, Bursa, Turkey2Bursa City Hospital, Department of Internal Medicine, Division of Nephrology, Bursa, Turkey3Bursa City Hospital, Department of Medical Pathology, Bursa, Turkey4Bursa City Hospital, Department of Radiology, Bursa, Turkey5Acıbadem International Hospital, Department of Medical Pathology, Istanbul, Turkey
Dung beetle serve as valuable indicators for studying environmental changes and as model systems for exploring ecosystem functionality. By analyzing the diversity and composition of gut microbiota in Catharsius molossus under starvation and refeeding conditions, this study investigates the effects of dietary states on the gut microbiota of these insects. Artificial rearing methods, along with 16S rRNA high-throughput sequencing and bioinformatics, were used to analyze Catharsius molossus gut microbiota under varying dietary conditions. The results indicate that at the phylum and genus levels, the gut microbiota of Catharsius molossus under refeeding conditions is more diverse than that under starvation conditions, with seven phyla and twenty-two genera showing significant differences (P < 0.05). In terms of functional prediction, the predicted functional genes of the gut microbiota were annotated to the KEGG database, revealing significant differences in thirty-two metabolic pathways at the third level (P < 0.05). Furthermore, it provides functional prediction information related to specific microbial taxa. Additionally, Dysgonomonas is speculated to participate in nitrogen fixation, and the gut microbiota of Catharsius molossus may potentially serve as a source of antimicrobial agents like anshanmycin. These findings provide novel insights into Coleoptera ecosystem microbial interactions and offer theoretical support for future applications.
BACKGROUND There is increasing concern that a significant proportion of randomised controlled trials (RCTs) included in Cochrane reviews may not be trustworthy. Applying a trustworthiness screening tool (TST) has already had a clinically important effect on several reviews published by the Cochrane Pregnancy and Childbirth Group. OBJECTIVES We wanted to assess the impact of removing untrustworthy RCTs from already- published Cochrane reviews on a defined clinical area (ante- and post-natal nutritional interventions). METHODS We applied the tool to 18 Cochrane reviews (375 RCTs). The tool had four domains: i) is the research governance trustworthy; ii) are the baseline characteristics trustworthy; iii) is the study feasible; iv) are the results plausible?). When additional information was needed, authors were contacted using a standard template. At least two attempts were made to contact the authors. At the end of the evaluation process each study was classified as: i) included (YES to all domains); ii) excluded (retracted study); or iii) awaiting classification (any NO to the TST questions). RESULTS 95/375 studies (25%) were removed, affecting 14/18 (78%) reviews. 13/18 reviews (72%) showed a difference in the Summary of Findings tables (direction and size of effects and/or GRADE ratings). 6/18 Cochrane reviews (33%) were judged to require updating because of important differences in either in their conclusions, implication for practice, and/or implication for research. CONCLUSIONS Formal assessment of trustworthiness and inclusion only of studies that satisfy prespecified criteria for trustworthiness affect conclusions in a relatively large number of Cochrane reviews, with potentially important clinical implications for practice and research. The lack of consensus regarding the best tool(s) for assessing trustworthiness cannot be an excuse for ignoring this issue in future Cochrane reviews.
Background Eating disorders are prevalent in the adolescent and young adult population, with 2.7% of adolescents effected. The American Academy of Pediatrics recommends yearly screening for eating disorders in adolescents. Even with this recommendation, eating disorders often go underdiagnosed. AYAs with cancer possess several risk factors for eating disorders that may place them at an even higher risk, including receiving weight-altering therapies and having their weight/nutrition emphasized. Since these patients see their oncology team frequently, oncology clinics are opportune settings for eating disorder screening. This describes a single-institution study to implement screening for eating disorders in AYA patients in an oncology clinic. Procedures During regularly scheduled oncology visits, eligible patients were given the SCOFF questionnaire. Patients with an oncologic diagnosis aged 13 and older were screened. Patients with known eating disorders and patients receiving cytotoxic therapy were excluded. The questionnaire was scored by a study team member. Patients with a positive screening were referred to adolescent medicine. Results 163 eligible patients filled out the SCOFF questionnaire with 11 positive results (6.75%). Conclusions Our results demonstrate that eating disorder screening was successfully implemented in our pediatric oncology clinic. With a rate more than double than the general population, we observed that AYA patients with a history of cancer are indeed at a higher risk for eating disorders and should undergo routine screening. Since these patients have frequent oncology appointments, oncology clinics should implement screening for eating disorders. Further studies are needed to develop appropriate screening methods for on therapy patients.
The study of the diet of extreme specialist species can help to understand the selective pressures that modulate the trophic strategies of raptors. This article provides insight into the trophic strategy of a little-known top predator and allows for a better understanding of the selective pressures that shape its diet. We studied the diet of European honey-buzzards, a raptor specialized in the consumption of social wasp brood. The ratio of predator to prey biomasses is one of the highest among raptors. We studied some factors that affect the energy demand of pairs which influence the diet composition and the daily rate of prey delivery to the nest. We explore hypotheses about the role of native and exotic vespids in the diet and the influence of the number and age of nestlings on diet composition, daily rate of prey delivery, and size of combs delivered. We installed trail cameras in 24 honey-buzzards nests in north-western Spain in 2018-2021. We estimated the proportion and daily rate of delivery of native common-wasps (Vespula vulgaris), invasive Asian-hornets (Vespa velutina), reptiles, and birds and the honey-buzzard´s preferences for vespid species. We performed LMMs, GLMMs, and MLRMs to analyse relationships between response variables and predictors. We identified 4611 prey. Honey-buzzards mainly consumed vespids (82% of prey). Common-wasps and Asian- hornets were almost the only two vespids consumed. The invasive hornet was the second most important prey consumed, but common-wasps were preferred. Vespids were more important as the age and number of nestlings increased. Our results suggest that the honey-buzzard´s diet is the adaptive result of the conflict between being a median-sized insect-eating migratory nidicolous raptor and collecting enough morsels for the growth of its nestlings, supporting the prey size and ingestion rate hypothesis. We discuss implications of our findings for the management of the invasive wasp
Muscle-specific kinase myasthenia gravis (MuSK MG) is caused by autoantibodies against MuSK in the neuromuscular junction (NMJ). MuSK MG patients have fluctuating, fatigable weakness, in particular of bulbar muscles. Severity differs greatly between patients, in spite of comparable autoantibody levels. One explanation for inter-patient and inter-muscle variability in sensitivity might be variations in compensatory muscle responses. Previously, we developed a passive transfer mouse model for MuSK MG. In preliminary ex vivo experiments we observed that muscle contraction, in particular of mice with milder myasthenia, had become partially insensitive to μ-Conotoxin-GIIIB, a blocker of skeletal muscle NaV1.4 voltage-gated sodium channels. We hypothesized that changes in NaV channel expression profile, possibly co-expression of (μ-Conotoxin-GIIIB insensitive) NaV1.5 type channels, might lower the muscle fibre’s firing threshold and facilitate neuromuscular synaptic transmission. To test this, we here performed passive transfer in mice, using ‘high’, ‘intermediate’ and ‘low’ dosing regimens of purified MuSK MG patient IgG4 and compared myasthenia levels, μ-Conotoxin-GIIIB resistance, muscle fibre action potential characteristics and firing thresholds. High- and intermediate-dosed mice showed clear, progressive myasthenia, not seen in low-dosed animals. However, diaphragm NMJ electrophysiology demonstrated almost equal myasthenic severities amongst all regimens. Nonetheless, low-dosed mouse diaphragms showed a much higher degree of μ-Conotoxin-GIIIB resistance. This was not explained by upregulation of Scn5a (the NaV1.5 gene), lowered muscle fibre firing thresholds or histologically detectable upregulated NaV1.5 channels. It remains to be established which factors are responsible for the μ-Conotoxin-GIIIB insensitivity and whether the NaV repertoire change is compensatory beneficial, or a bystander effect.
We compared voluntary drive and corticospinal responses during eccentric (ECC), isometric (ISO) and concentric (CON) muscle contractions to shed light on the mechanisms underpinning the greater force production despite lower electromyographic activity (EMG) commonly reported in ECC than ISO and CON. Sixteen participants (20-33 y) performed ISO and isokinetic (30˚/s) CON and ECC knee extensor contractions between 110˚ and 40˚ knee flexion, while EMG was recorded from vastus lateralis. Voluntary activation (VA) was measured during ISO, CON and ECC maximal voluntary contractions (MVCs). Transcranial magnetic stimulation elicited motor evoked potentials (MEPs) and corticospinal silent periods (CSP) during MVCs and submaximal contractions (30% maximum), and short-interval intracortical inhibition (SICI) in submaximal contractions. MVC torque was greater (P<0.01) during ECC (302.6±90.0 Nm) than ISO (269.8±81.5 Nm) and CON (235.4±78.6 Nm), but VA was lower (P<0.01) for ECC (68.4±14.9%) than ISO (78.3±13.1%) and CON (80.7±15.4%). Additionally, EMG/torque was lower (P<0.02) for ECC (1.9±1.1 μV.Nm-1) than ISO (2.2±1.2 μV.Nm-1) and CON (2.7±1.6 μV.Nm-1), CSP was shorter (p<0.04) for ECC (0.097±0.03 s) than ISO (0.109±0.02 s) and CON (0.109±0.03 s), and MEP amplitude was lower (P<0.01) for ECC (3.46±1.67 mV) than ISO (4.21±2.33 mV) and CON (4.01±2.06 mV). Similar results were found for EMG/torque and CSP during 30% contractions, but MEP amplitude and SICI showed no differences among contractions (p>0.05). Reduced VA during ECC may be at least partly explained by lower corticospinal excitability, while a shorter CSP may reflect extra muscle spindle excitation of the motoneurons from muscle lengthening, rather than reduced corticospinal inhibition.
Rationale. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) can provide precise analysis of a protein’s conformational dynamics across varied states, such as heat-denatured vs. native protein structures, localizing regions that are specifically affected by such conditional changes. Maximizing protein sequence coverage provides high confidence that regions of interest were located by HDX-MS, but one challenge for complete sequence coverage is N-glycosylation sites. The deuteration of peptides post-translationally modified by asparagine-bound glycans (glycopeptides) has not always been identified in previous reports of HDX-MS analyses, causing significant sequence coverage gaps in heavily glycosylated proteins and uncertainty in structural dynamics in many regions throughout a glycoprotein. Methods. We detected deuterated glycopeptides with a Tribrid Orbitrap Eclipse mass spectrometer performing data-dependent acquisition. An MS scan was used to identify precursor ions, if high-energy collision-induced dissociation (HCD) MS/MS of the precursor indicated oxonium ions diagnostic for complex glycans then electron transfer low-energy collision-induced dissociation (EThcD) MS/MS scans of the precursor identified the modified asparagine residue and the glycan’s mass. As in traditional HDX-MS the identified glycopeptides were then analyzed at the MS level in samples labeled with D 2O. Results. We report HDX-MS analysis of the SARS-CoV-2 spike protein ectodomain in its trimeric pre-fusion form, which has 22 predicted N-glycosylation sites per monomer, with and without heat treatment. We identified glycopeptides and calculated their average isotopic mass shifts from deuteration. Inclusion of the deuterated glycopeptides increased sequence coverage of spike ectodomain from 76% to 84%, demonstrated that glycopeptides had been deuterated, and improved confidence in results localizing structural re-arrangements. Conclusion. Inclusion of deuterated glycopeptides improves the analysis of the conformational dynamics of glycoproteins such as viral surface antigens and cellular receptors.
Affordances, the opportunity for action offered by the environment to an agent, are vital for meaningful behavior and exist in every interaction with the environment. Regarding its temporal mechanism, some studies suggest that affordance perception is an automated process that is independent from the visual context and bodily interaction with the environment, while others argue that it is modulated by the visual and motor context in which affordances are perceived. We aims to resolve this debate by examining affordance automaticity from the perspective of sensorimotor time windows. We replicated a previous study on affordance perception in which participants actively moved through doors of different width in VR environments. To investigate the impact of different forms of bodily interactions with an environment, i.e., the movement context (physical vs. joystick movement), we used the identical virtual environment from Djebbara and colleagues (2019) but displayed it on a 2D screen with participants moving through different wide doors using the laptop keyboard. We compared components of the event-related potential (ERP) from the continuously recorded electroencephalogram (EEG) that were previously reported to be related to affordance perception of architectural transitions (passable and impassable doors). Comparing early sensory and later motor-related ERPs, our study replicated ERPs reflecting early affordance perception but found differences in later motor-related components. It indicates a shift from automated perception of affordances during early sensorimotor time windows to movement context dependence of affordance perception at later stages suggesting that affordance perception is a dynamic and flexible process that changes over sensorimotor stages.
Endometrial cancer is the most prevalent gynaecological cancer globally. Its association with obesity and metabolic diseases is a key aetiology, increasingly among younger females. Early diagnosis and improved treatment decisions are crucial for these women whose outcomes could be improved by discovering new biomarkers. We took a new approach to extracellular vesicle (EV) biomarker discovery - profiling the proteome of enriched EVs isolated directly from frozen biobanked endometrial cancers. Nine tissue pools, each generating collagenase-digested tissue and matched small EVs, were analysed using label-free proteomics. Three clinical subgroups: Endometrioid low BMI (body mass index), Endometrioid high BMI, and Serous, irrespective of BMI, were compared to identify shared secreted proteins, proteins associated with histological subtype, and proteins related to BMI. EVs were enriched for common EV markers and large secreted proteins. Cell lysates were enriched in mitochondrial and blood proteins. EV protein profiles were most different between the high BMI subgroup and the others, highlighting a significant influence of comorbidities on the intra-tumoural EV secretome. Proteins differentially abundant between subgroups in tissues were strikingly not also differential in the matched EVs. This work has identified secreted proteins implicated in the complex pathophysiology of endometrial cancer and pinpointed candidate biomarkers for diagnosis.
An easy-to-implement noise estimation method for tuning state estimators is proposed. It outperforms benchmark methods in terms of accuracy or computational cost both in theory and in a case study. We assume parametric uncertainty in the process model, which we transform into noise statistics using the generalized unscented transformation (GenUT). While most other methods estimate only the noise covariance, we also estimate the mean. Our tuning method is suitable for input-output models, demonstrated through a case study involving process simulators and industrial data. We present a theoretical analysis of our method, which is based on splitting one large GenUT to two smaller GenUTs. This results in two theorems: i) mean approximations for the two systems are equal and ii) covariance approximations are similar under certain mild conditions. These theorems confirm the validity of our method, and we discuss their potential to realize a numerically stable GenUT for high-dimensional systems.