A document by Amal ELLEUCH. Click on the document to view its contents.

IntroductionAlpha-Ketoglutarate dehydrogenase (2-KGD) deficiency, a rare disorder of the Krebs cycle, was described for the first time as a progressive neurodegenerative disease with 2-ketoglutaric aciduria in two siblings of a Tunisian consanguineous family by Kohlschutter and colleagues (1982) [1]. Alpha-Ketoglutarate dehydrogenase is a multienzyme complex that catalyzes the oxidative decarboxylation of a-ketoglutarate to succinyl-coenzyme A in the tricarboxylic acid cycle. It is made up of three components:E1 a-ketoglutarate lipoamide oxidoreductase.E2 dihydrolipoamide succinyltransferase transfers the carboxyl group to the coenzyme A moiety.E3 dihydrolipoamide dehydrogenase transfers reducing oxygen from E2 to a flavoprotein and finally to nicotinamide-adenine dinucleotide.Onset and clinical presentation of the reported cases of the (2-KGD) deficiency are heterogeneous, with mostly severe neurological impairment, including muscular hypotonia, developmental delay, extrapyramidal symptoms, ataxia, increased extensor tonus, and seizures. The age of onset varied between the neonatal period and 16 months. The oldest child reported died at the age of 10 years [1, 2, and 3].

Alzheimer’s disease (AD), a progressive neurodegenerative health condition symptomized by dementia is characterized majorly by the accumulation of Aβ peptides and Tau hyperphosphorylation. AD also progresses as a result of oxidative stress caused by an increase in the expression of Monoamine Oxidase B (MAO-B). Therefore, possible drug candidates which can be used to inhibit the expression and activity of MAO-B, are being investigated. Plant sources are a great resource for discovering novel compounds in the treatment of disease conditions. One such plant known for its use in CNS-related conditions and has been investigated for the presence of bioactive compounds is Leonotis leonurus R. Br. (Lamiaceae). The most probable macromolecular targets of 36 bioactive compounds identified from Leonotis leonurus were predicted using swisstargetprediction.ch. Compounds predicted to target MAO-B and microtubule associated protein tau (MAPT) were then docked on the 3D molecular structure of MAO-B (PDB ID:2vrl) in a molecular operating environment (MOE) in comparison with known inhibitors. In vitro activity of the resulting compounds against MAO-B enzymes was then conducted and the results were compared. Out of the six possible compounds, vitexin was the only compound observed to have interacted with the amino acids at the active site in silico and have inhibitory activity against MAO-B in vitro.

The identification of multiple-input multiple-output (MIMO) systems is an important part of designing complex control systems. This paper studies an auxiliary model least squares iterative (AM-LSI) algorithm for MIMO systems. With the expansion of the system scale and limitations of the computer resources, there is an urgent need for an identification algorithm that provides higher computational efficiency. To address this issue, this paper further derives a hierarchical identification model and proposes a new auxiliary model hierarchical least squares iterative (AM-HLSI) algorithm for MIMO systems by applying the hierarchical identification principle. Through the analysis of the computational efficiency, the AM-HLSI algorithm has higher computational efficiency than the AM-LSI algorithm. Additionally, the feasibility of the AM-LSI and AM-HLSI algorithms is validated by a simulation example.

Heavy winds hinder the execution of essential tasks for Rotary Unmanned Aerial Vehicles (RUAVs) such as mountain rescue operations or civil engineering assessments during typical Northern Irish winters. This study uses Reinforcement Learning (RL) methods to select controller gains, enhancing RUAV stability under challenging wind conditions, employing a Deep Deterministic Policy Gradient (DDPG) agent over conventional and optimal controllers. The proposed DDPG agent enables the controller to be built as a “Black Box” approach, where the agent can adapt to slight changes or model uncertainty in a real system enabling a more robust controller. Simulations carried out on Full State Feedback, Full State Compensator and Linear Quadratic Gaussian controllers tuned by a variety of techniques revealed that RL out-performed conventional manual tuning by 26% and Particle Swarm Optimization by 19% in performance measured in settling time.

Chagas disease is caused by the Trypanosoma cruzi parasite and is transmitted by infected triatomine bugs. This infection affects approximately 8 million people in the Americas, and due to globalization and displacement, it is becoming increasingly common to find infected patients worldwide. Diagnosis of the disease in its acute form is relatively simple, as the parasite can be detected in peripheral blood smears, and symptoms are visible. However, in its chronic condition, the parasite is almost undetectable, and indirect tests are necessary to determine the presence of antibodies in infected patients. It is important to note that a single test is not enough to confirm the disease, as a second serological test should confirm the diagnosis. If the results are contradictory, a third test should be performed to solve the problem. Unfortunately, laboratories may not have access to all necessary tests in many rural areas where the disease is more frequent. Rapid tests to diagnose this disease present problems, such as significant variations in sensitivity and specificity in different countries. Therefore, searching for new biomarkers that allow for optimal correlation is essential. In this work, we have searched scientific literature from the last years for mentions of novel biomarkers for diagnosis, treatment follow-up, and prediction of cardiac complications in Chagas disease in its chronic phase.

The quarantining of Ebola virus disease (EVD) infectious individuals in hospitals and controlled environments largely depends on the availability of unoccupied habitable beds in the hospitals and environments. This work addresses the role of limited hospitalisation on the transmission of EVD using a unique compartmental model incorporating hospital beds’ dynamics within the hospital compartment. We consider a bed-dependent hospitalisation function and assume that although the bed growth rate is logistic in nature, it only occurs via the refurbishment of unhabitable beds. The epidemic threshold, the conditions for the local stability of the disease-free equilibrium, and the existence of a backward bifurcation in the system are determined. The model is fitted to data from the Democratic Republic of Congo (DRC) and sensitivity analysis is carried out to determine important parameters that should be targeted when considering interventions. Our results suggest that in the case of an EVD outbreak, unhabitable beds should be continually refurbished if the disease must be contained.

Introduction and objectives：Traditional transcatheter closure of atrial septal defect (ASD) via the femoral vein carries risk of radiation damage. Transcutaneous closure of ASD under echocardiography guidance avoids radiation exposure and can be gradually applied. An alternative is to transcutaneous closure of ASD trans-jugular with an adjustable curved sheath under echocardiography guidance. Methods: We retrospectively studied all cases of trans-jugular transcutaneous closure of ASD with an adjustable curved sheath under echocardiography guidance in the Heart Center of Henan Province People’s Hospital between 2016 and December 2022. Results: 156 patients were included, 74 males and 82 females. Mean age was 6.9 ± 7.4 years and weight 23.7 ± 14.6 kg. Mean sizes of the ASD and occluder were (9.7 ± 4.7) mm and (14.1 ± 5.7) mm. The mean operation time was (49.6 ± 29.2) min. No complications such as atrioventricular block, reoperation, or pericardial effusion occurred. There are 3 patients had a residual shunt. All patients were followed-up for (38.7 ± 11.0)months. The 3 patients with residual shunt had self-closed at the 3-6-12months follow-up. There was no complication at follow-up. Conclusion: Trans-jugular transcutaneous closure of ASD with adjustable curved sheath under echocardiography guidance is safe, effective and minimally invasive.

A document by Daniel Thomas Skinner. Click on the document to view its contents.

Interdisciplinary teams are on the rise as scientists attempt to address complex environmental issues. While the benefits of Team Science approaches are clear, researchers often struggle with its implementation, particularly for new team members. The challenges of large projects often weigh on the most vulnerable members of a team: trainees, including undergraduate students, graduate students, and post-doctoral researchers. Trainees on big projects have to navigate their role on the team, with learning project policies, procedures, and goals, all while also training in key scientific tasks such as co-authoring papers. To address these challenges, we created and participated in a project-specific, graduate-level Team Science course. The purposes of this course were to: (1) introduce students to the goals of the project, (2) build trainees’ understanding of how big projects operate, and (3) allow trainees to explore how their research interests dovetailed with the overall project. Additionally, trainees received training regarding: (1) diversity, equity & inclusion, (2) giving and receiving feedback, and (3) effective communication. Onboarding through the Team Science course cultivated psychological safety and a collaborative student community across disciplines and institutions. Thus, we recommend a Team Science course for onboarding students to big projects to help students establish the skills necessary for collaborative research. Project-based Team Science classes can benefit student advancement, enhance the productivity of the project, and accelerate the discovery of solutions to ecological issues.

The Neretva dwarf goby Orsinigobius croaticus (Gobiiformes, Gobionellidae) is an endemic fish native to the freshwaters of the Adriatic Basin in Croatia and Bosnia and Herzegovina. Due to its limited distribution range, specific karst habitat and endangered status, laboratory studies on reproductive biology are scarce. We investigated the sound production and acoustic behaviour of this species during reproductive intersexual laboratory encounters. We performed dissection and micro-computed tomography (μCT) scanning of the pectoral girdle to explore the anatomy of its putative sound producing mechanism. To study interspecific acoustic differences and determine whether acoustic features can discriminate among species, comparative analysis was conducted on sounds produced by closely related soniferous sand gobies. Our results indicate that males of the O. croaticus emit pulsatile sounds composed of a variable number of short (~ 15 ms) consecutive pulses when interacting with females, usually during the pre-spawning phase in the nest, but also during courtship outside the nest. Pulsatile sounds were low-frequency and short pulse trains (~ 140 Hz, < 1000 ms), and spectro-temporal parameters were correlated with physical traits and water temperature. Male visual behaviour rate was higher when co-occurring with sounds and females entered the male’s nest significantly more frequently when sounds were present. Male sound production was accompanied by movements such as head thrust and fin spreading. μCT scans and dissections suggest that O. croaticus shares certain anatomical similarities of the pectoral girdle (osseous elements and arrangement of levator pectoralis muscles) to previously studied sand gobies. Multivariate comparisons, using sounds produced by eight soniferous European sand gobies, effectively distinguished soniferous (and sympatric) species based on acoustic properties. Discrimination success decreased when temperature-dependent features (sound duration and pulse repetition rate) were excluded from analysis. Therefore, we suggest both spectral and temporal features are important for acoustic differentiation of sand gobies.

Aim The Arctic ecosystems are exposed to amplified climate warming and in some regions to rapidly developing economic activity. This study aims to identify, model and map the patterns of community-level plant species richness in the Western Siberian Arctic and the environmental and anthropogenic factors driving those patterns. With our results and methods, we aim at contributing towards conservation efforts for arctic species richness. Location Western Siberian Arctic, Russia. Methods We investigated the relative impact of environmental and anthropogenic factors on community-level plant species richness of the Western Siberian Arctic, using macroecological models trained with an extensive, newly assembled geobotanical dataset. We included vascular plants, mosses and lichens in our analysis, as non-vascular plants substantially contribute to species richness and ecosystem functions in the Arctic. Results We found that the mean community-level plant species richness in this vast Arctic region does not decrease with increasing latitude. Instead, we identified an increase in species richness from South-West to North-East, which can be explained by climatic, topographical and anthropogenic factors. We found that the lowest species richness is associated with a medium (≈ 35 km) distance to infrastructure while neighboring (<10 km) and remote (≈ 100 km) areas have relatively high species richness. We also show that the existing protected areas cover only a small part of the areas with the highest species richness. Conclusions Our results reveal complex spatial patterns of community-level species richness distribution in the Western Siberian Arctic. We suggest that the impact of economic activities on species richness is ambiguous and not limited to areas directly affected by infrastructure. We show that economic activities along with other factors contribute to heterogeneous distribution of species richness on a broad scale. Our approach and results can be used to develop nature protection strategies for other arctic regions facing similar challenges.

Purpose: The purpose of this study is to identify adverse drug events signals of tamoxifen through analyze the US FDA Adverse Event Reporting System (FAERS) data from 2015 to 2020. Method: Disproportionality analysis was used to identify adverse drug events(AEs) signals associated with tamoxifen as the primary suspect drug from January 1, 2015 to June 30, 2020. AEs are preferred terms (PTs) defined in MedDRA23.1 and the drug name was standardized by MedEx_UIMA_1.3.8. We used frequentist approaches and Bayesian approaches, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR) and Bayesian confidence propagation neural network (BCPNN) to determine signals. Signals were defined as the number of reports ≥ 3 and the lower limit of 95% confidence intervals (CI) of ROR ≥ 1, PRR ≥ 2, IC > 0, and chi-squared of PRR ≥4. Results: A total of 1496 adverse event reports associated with tamoxifen were involved in the statistic analysis. The male to female ratio of 1496 reports was 1:16.29(234 reports without gender information). The most frequently reported outcome except “Other Serious” is “Hospitalization-Initial or Prolonged”(17.98%). a total of 77 signals were identified, including“Malignant neoplasm progression”, “Hepatic cirrhosis”, “Non-alcoholic steatohepatitis”and so on, involving 18 System Organ Classes(SOCs). Conclusions: Medical staff should pay special attention to the nervous system adverse events caused by tamoxifen, especially in high-risk patients with Alzheimer’s disease. And the reason of it may be that tamoxifen inhibit estrogen in brain.

The plants’ geographical distribution is affected by natural or human-induced climate change. Numerous studies at both the global and regional level currently focus on the potential changes in plant distribution areas. Ecological niche modeling can help predict the likely distribution of species according to environmental variables under different climate scenarios. In this study, we predicted the potential geographic distributions of Quercus ilex L. (holm oak), a keystone species of the Mediterranean ecosystem, for the Last Interglacial period (LIG: ~120 Ka), the Last Glacial Maximum (LGM: ~22 Ka), mid-Holocene (MH: ~6 Ka), and future climate scenarios (Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios) for years 2050-2070 obtained from CCSM4 and MIROC-ESM global climate scenarios respectively. The models were produced with algorithms from the R-package “biomod2” and assessed by AUC of the Receiver Operating Characteristic plot and True Skill Statistics. Apart from BIOCLIM (SRE), all model algorithms performed similarly and produced projections that are supported by good evaluation scores, although Random Forest (RF) slightly outperformed all the others. Additionally, distribution maps generated for the past period were validated through a comparison with pollen data acquired from the Neotoma Pollen Database. The results revealed that southern areas of the Mediterranean Basin, particularly coastal regions, served as long-term refugia for Q. ilex, which was supported by fossil pollen data. Furthermore, the models suggest long term refugia role for Anatolia and we argue that Anatolia may have served as a founding population for the species. Future climate scenarios indicated that Q. ilex distribution varied by region, with some areas experiencing range contractions and others range expands. This study provides significant insights into the vulnerability of the Q. ilex to future climate change in the Mediterranean ecosystem and highlights the crucial role of Anatolia in the species’ historical distribution.

Background: The cause for anaphylaxis cannot be identified after extensive evaluation in a large proportion of patients, who are classified as having ‘idiopathic anaphylaxis’ (IA). As food consumption patterns, genetic background, and environmental factors can lead to differences in allergen sensitization patterns in different regions, we sought to identify the aetiology of IA in cohort of Sri Lankan patients. Methods: Of the patients referred to our clinic following anaphylaxis, 65 were recruited as a cause could not be identified. The events that led to the episode of anaphylaxis, the triggers, the severity of symptoms and treatment received were recorded and skin prick test, ISAC ImmunoCAP test and serum tryptase was carried out. Results: Of the 65 patients, 42/65 (64.6%) were females and 49/65 (75.38%) were adults. 46/65 (70.8%) had grade II anaphylaxis and 34/65 (52.3%) were found to have specific IgE to alpha-gal, with symptoms occurring 0.5 to 6 hours since ingestion of food. Of those who had specific IgE to alpha-gal, 12 (35.3%) had consumed red meat and 10 (29.4%) milk products (3 had consumed fermented buffalo milk), before the episode of anaphylaxis. Difficulty in breathing, swelling of lips and syncope was significantly higher in those who were not sensitized to alpha-gal, while diarrhoea and abdominal pain were more common in those sensitized to alpha-gal, although this was not significant. Conclusion: A large proportion of patients presenting with IA were found to be sensitized to alpha-gal, which was the likely cause of their anaphylaxis.

This article describes a numerical method based on the dual reciprocity boundary elements method (DRBEM) for solving some well-known nonlinear parabolic partial differential equations (PDEs). The equations include the classic and generalized Fisher's equations, Allen-Cahn equation, Newell-Whithead equation, FitzHugh-Nagumo equation and generalized FitzHugh-Nagumo equation with time-dependent coefficients. The concept of the dual reciprocity is used to convert the domain integral to the boundary that leads to an integration free method. We employ the time stepping scheme to approximate the time derivative, and the linear radial basis functions (RBFs) are used as approximate functions in presented method. The nonlinear terms are treated iteratively within each time step. The developed formulation is verified in some numerical test examples. The results of numerical experiments are compared with analytical solution to confirm the accuracy and efficiency of the presented scheme.

In this paper we apply the boundary elements method (BEM) and the dual reciprocity boundary elements method (DRBEM) for the numerical solution of two-dimensional time-fractional partial differential equations (TFPDEs). The fractional derivative of problem is described in the Caputo sense. In BEM, the main equation deduces to solving the Helmholtz equation in each time step. Therefore, we should compute the domain integral in each time step. So, we presented an approach to compute the domain integral with no singularity. On the other hand the DRBEM has the flexibility of discretizing only the boundary of the computational domain and evaluates the solution at any required interior point. We employ the radial basis functions (RBFs) for interpolation of the inhomogeneous and time derivative terms. The proposed method is employed for solving some problems in two-dimensions on unit square and some other complex regions to demonstrate the efficiency of the proposed method.

Drought and climate change are important factors to include in any hydrologic analysis. Current weather-related events in California, such as the extended drought and recent multiple atmospheric rivers, demonstrate how quickly hydrologic conditions can change. A lag(1) autocorrelation analysis of California Climate Division 2 (Sacramento Drainage) using monthly Palmer Hydrologic Drought Index (PHDI) values was conducted to find data ranges, persistence of conditions, along with seasonal and historical drought patterns. Results show distinct conditions within the hydrologic-climatic system which include periods of (a) persistent drought, (b) persistent wet, (c) transition from drought to wet, and (d) transition from wet to drought. Month-to month PHDI changes are quantified using a summation infographic based on the autocorrelation scatterplot.

The extreme power output scenarios of renewable energy sources (RES) proposed new challenges to the safe and stable operation of the power system. Transmission expansion planning (TEP) with large-scale RES grid integration needs considering the risk of extreme scenarios. In this paper, an adaptive decision-making approach for the TEP problem based on planning-risk assessment-replanning iterative process is proposed. The method obtains massive temporal and spatial correlated wind-photovoltaic (PV) power output scenarios by generalizing the historical data to describe the uncertainties. A data-driven load loss risk assessment model (RAM) based on the power system’s actual operating state is built, referring to the degree of extreme scenario risks on the balance of supply and demand, and the probability of extreme scenario occurrence. The planning decision is progressively revised according to the risk assessment result. The Garver’s 6-bus system and the IEEE RTS 24-bus system are adopted as simulation cases. The results show that the optimal expansion plans achieve a balance between the economy and robustness, which verifies the effectiveness of the proposed method.

with other laboratory and clinical investigations. Early and accurate diagnosis of inherited conditions generally leads to better medical care for patients and their families, with improved knowledge of the natural history of the condition and early intervention. It is therefore essential that equitable access to such testing is established for indigenous and isolated populations, in order to further narrow the health disparity gap. Although supported by funding from a few sources, this study signals a success for the Silent Genomes Project, with one of the cases having been identified by whole genome sequencing within that project, after negative whole exome sequencing. Furthermore the study has potential life-changing clinical consequences and provides starting points for possible interventions for respiratory medicine in the Inuit population. These include increased awareness of the possibility of PCD in patients presenting with neonatal respiratory distress, bronchiectasis or otitis media leading to early intervention; and in conjunction with Inuit organizations and public health officials, targeted analysis of the DNAH11 variant in the population with the possible introduction of newborn screening for PCD.

Background：Despite the challenge of associating childhood risk factors with adult asthma, a systematic synthesis of evidence on the risk factors is lacking. We performed a systematic review and meta-analysis of the association between childhood risk factors and adult asthma. Methods：We systematically searched the PubMed and Web of Science electronic databases from the inception to our last search date (10 November 2022). The search strategy included key words for risk childhood risk factors and adult asthma. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies. Results: Of 25 eligible articles, 18 domains of childhood risk factors were assessed. Bronchiolitis/wheezing (pooled adjusted OR=5.32; 95% CI: 2.83-10.02; I 2=58%; number of outcomes [N] =7), eczema (pooled adjusted OR=2.01; 95% CI: 1.42-2.84; I 2=79%; N=8), hay fever (pooled adjusted OR=3.31; 95% CI: 2.26-4.85; I 2=0%; N=2), positive reaction of skin prick test (SPT)(pooled adjusted OR=2.37; 95% CI: 1.18-4.77; I 2=54%; N=3), airway hyperresponsiveness (AHR)(pooled adjusted OR=2.73; 95% CI: 1.52-4.88; I 2=0%; N=2) and pool lung function (pooled adjusted OR=2.88; 95% CI: 1.41-5.87; I 2=0%; N=2) during childhood increased the risk of adult asthma. Association of childhood asthma and rhinitis with adult asthma needs more studies to confirm. Childhood body mass index (BMI) wasn’t found to be related to adult asthma (pooled adjusted OR=1.06; 95% CI: 0.57-1.97; I 2=78%; N=3). The evidence was insufficient to draw conclusion for passive smoking, household economical condition, keeping pets, girls matured early, slept for insufficient durations, being abused, pneumonia, adenoidectomy and/or tonsillectomy, cognitive ability. Conclusion: Childhood bronchiolitis/wheezing, eczema, hay fever, positive reaction of SPT, AHR and poor lung function were associated with an increased risk of adult asthma. These identified risk factors would be helpful for the early prevention of the adult asthma. And future studies might need to clarify and supplement existing conclusions from more aspects.

Background: Multiple Sclerosis (MS) is a chronic disease with a high prevalence of neuropsychiatric symptoms. Mindfulness is a practice that encourages individuals to cultivate a present-focused, acceptance-based approach for managing neuropsychiatric symptoms. Its positive effect on MS has been demonstrated, but learning such technique is expensive and time-consuming. In this study, we investigated the feasibility and efficacy of an 8-week, at-home, technology-supported mindfulness program in a cohort of MS patients. Methods: The study included two visits, one at baseline and another after the mindfulness program. We measured adherence to the proposed mindfulness treatment and its effect on different neuropsychological scales and in terms of quantitative EEG parameters. All participants received a smart biofeedback device to be used during the therapeutic program consisting of daily meditative exercises. Results: Twenty-nine patients were recruited for the present study. Among them, 27 (93%) completed the entire program and 17 (63%) completed more than 80% of the scheduled sessions. We observed a statistically significant reduction of the Ruminative Response Scale score and a significant increase in the Digit Span Backward. Regarding neurophysiological data, we found a significant reduction of the whole-scalp beta and parieto-occipital theta power post intervention. Conclusion: Our results show that an at-home, technology-supported mindfulness program is feasible for people with MS. The efficacy in terms of reappraisals of stress, cognitive and emotional coping responses is also supported by our neurophysiological data. Further studies are warranted to better explore the role of such approaches in managing the psychological impact of MS diagnosis.

Introduction: Wearable Cardioverter Defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. Methods: In WEARIT-II, the cumulative probability of any sustained or non-sustained VT/VF (WCD-treated and non-treated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method by prior AF, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by prior AF using negative binomial regression. Results: WEARIT-II enrolled 2000 patients, 557 (28%) of whom had AF prior to enrollment. Cumulative probability of any sustained or non-sustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p=0.001). Similarly, the recurrent rate of any sustained or non-sustained VT/VF was significantly higher in patients with prior AF vs. no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p=0.001). Patients with prior AF also had a significantly higher burden of any WCD-detected atrial arrhythmias/SVT/inappropriate therapy (183.2 events per 100 patient-years vs. 74.8 events per 100 patient-years, p<0.001). Conclusion: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.

Although herbivory and allelopathy play important roles in plant invasions, their roles in mediating the effect of plant diversity on invasion resistance remain unknown. We performed a two-year field experiment in which we manipulated plant-species richness, herbivory and allelopathy, and then experimentally invaded the plots with the invasive Solidago canadensis. One year after the start of the experiment, there was no significant effect of species richness on biomass of the invader, as a negative indirect effect of species richness via increase light interception was compensated by a positive direct effect. However, in the second year, the relationship was negative, in line with the diversity-invasibility hypothesis. The negative relationship was strongest when herbivory and allelopathy were not manipulated. Therefore, we conclude that joint effects of herbivory and allelopathic interactions between the native plants and the invader play a major role in the observed species richness-invasibility relationship.