Land-management options for greenhouse gas removal (GGR) include afforestation or reforestation (AR), wetland restoration, soil carbon sequestration (SCS), biochar, terrestrial enhanced weathering ...(TEW), and bioenergy with carbon capture and storage (BECCS). We assess the opportunities and risks associated with these options through the lens of their potential impacts on ecosystem services (Nature's Contributions to People; NCPs) and the United Nations Sustainable Development Goals (SDGs). We find that all land-based GGR options contribute positively to at least some NCPs and SDGs. Wetland restoration and SCS almost exclusively deliver positive impacts. A few GGR options, such as afforestation, BECCS, and biochar potentially impact negatively some NCPs and SDGs, particularly when implemented at scale, largely through competition for land. For those that present risks or are least understood, more research is required, and demonstration projects need to proceed with caution. For options that present low risks and provide cobenefits, implementation can proceed more rapidly following no-regrets principles.
Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not ...the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5-14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation.
Human activities have increased the intensity and frequency of natural stressors and created novel stressors, altering host–pathogen interactions and changing the risk of emerging infectious ...diseases. Despite the ubiquity of such anthropogenic impacts, predicting the directionality of outcomes has proven challenging. Here, we conduct a review and meta‐analysis to determine the primary mechanisms through which stressors affect host–pathogen interactions and to evaluate the impacts stress has on host fitness (survival and fecundity) and pathogen infectivity (prevalence and intensity). We assessed 891 effect sizes from 71 host species (representing seven taxonomic groups) and 78 parasite taxa from 98 studies. We found that infected and uninfected hosts had similar sensitivity to stressors and that responses varied according to stressor type. Specifically, limited resources compromised host fecundity and decreased pathogen intensity, while abiotic environmental stressors (e.g., temperature and salinity) decreased host survivorship and increased pathogen intensity, and pollution increased mortality but decreased pathogen prevalence. We then used our meta‐analysis results to develop susceptible–infected theoretical models to illustrate scenarios where infection rates are expected to increase or decrease in response to resource limitations or environmental stress gradients. Our results carry implications for conservation and disease emergence and reveal areas for future work.
Disruptions in host–pathogen interactions can negatively impact human and animal health, biodiversity conservation and ecosystem structure and function. We synthesized the current understanding of how human‐induced stressors affect host–pathogen interactions by altering (1) host density, (2) host defences and (3) pathogen infectivity. We then conducted a meta‐analysis of studies where impacts of host fitness (survival and fecundity) and pathogen prevalence and intensity were evaluated under control and stressful conditions (low resources, adverse environmental conditions and pollution). Responses varied according to stressor type: limited resources compromised host fecundity and decreased pathogen intensity, while environmental stressors (e.g., temperature) decreased host survivorship and increased pathogen intensity, and pollution increased mortality but decreased pathogen prevalence. To reveal scenarios where infection rates would increase or decrease in response to the simultaneous trait changes occurring over resource and environmental stress gradients, we incorporated our findings into two theoretical susceptible–infected models.
Pochonia chlamydosporia is an endophytic fungus used for nematode biocontrol that employs its cellular and molecular machinery to degrade the nematode egg-shell. Chitosanases, among other enzymes, ...are involved in this process. In this study, we improve the genome sequence assembly of P. chlamydosporia 123, by utilizing long Pacific Biosciences (PacBio) sequence reads. Combining this improved genome assembly with previous RNA-seq data revealed alternative isoforms of a chitosanase in the presence of chitosan. This study could open new insights into understanding fungal resistance to chitosan and root-knot nematode (RKN) egg infection processes.
The P. chlamydosporia 123 genome sequence assembly has been updated using long-read PacBio sequencing and now includes 12,810 predicted protein-coding genes. Compared with the previous assembly based on short reads, there are 701 newly annotated genes, and 69 previous genes are now split. Eight of the new genes were differentially expressed in fungus interactions with Meloidogyne javanica eggs or chitosan. A survey of the RNA-seq data revealed alternative splicing in the csn3 gene that encodes a chitosanase, with four putative splicing variants: csn3_v1, csn3_v2, csn3_v3 and csn3_v4. When P. chlamydosporia is treated with 0.1 mg·mL
chitosan for 4 days, csn3 is expressed 10-fold compared with untreated controls. Furthermore, the relative abundances of each of the four transcripts are different in chitosan treatment compared with controls. In controls, the abundances of each transcript are nil, 32, 55, and 12% for isoforms csn3_v1, csn3_v2, csn3_v3 and csn3_v4 respectively. Conversely, in chitosan-treated P. chlamydosporia, the abundances are respectively 80, 15%, 2-3%, 2-3%. Since isoform csn3_v1 is expressed with chitosan only, the putatively encoded enzyme is probably induced and likely important for chitosan degradation.
Alternative splicing events have been discovered and described in the chitosanase 3 encoding gene from P. chlamydosporia 123. Gene csn3 takes part in RKN parasitism process and chitosan enhances its expression. The isoform csn3_v1 would be related to the degradation of this polymer in bulk form, while other isoforms may be related to the degradation of chitosan in the nematode egg-shell.
Summary
Climate change makes plant‐parasitic nematodes (PPN) an increasing threat to commercial crops. PPN can be managed sustainably by the biocontrol fungus Pochonia chlamydosporia (Pc). Chitosan ...generated from chitin deacetylation enhances PPN parasitism by Pc. In this work, we investigate the molecular mechanisms of Pc for chitosan resistance and root‐knot nematode (RKN) parasitism, using transcriptomics. Chitosan and RKN modify the expression of Pc genes, mainly those involved in oxidation–reduction processes. Both agents significantly modify the expression of genes associated to 113 GO terms and 180 Pc genes. Genes encoding putative glycoproteins (Pc adhesives) to nematode eggshell, as well as genes involved in redox, carbohydrate and lipid metabolism trigger the response to chitosan. We identify genes expressed in both the parasitic and endophytic phases of the Pc lifecycle; these include proteases, chitosanases and transcription factors. Using the Pathogen—Host Interaction database (PHI‐base), our previous RNA‐seq data and RT‐PCR of Pc colonizing banana we have investigated genes expressed both in the parasitic and endophytic phases of Pc lifecycle.
Objective Superior laryngeal nerve (SLN) function is critical to laryngeal sensation. Sensory dysfunction in the larynx, mediated through the internal branch of the superior laryngeal nerve (iSLN), ...is thought to occur with aging and neurodegenerative disease. However, objective analysis of iSLN neurophysiology is difficult due to its anatomic location and small diameter. This study measures sensory nerve action potentials (SNAP) from the iSLN in a rat model. Methods SNAP data were obtained from two adult rat strains (Sprague–Dawley, SD and Fischer 344 × Brown Norway F1 Hybrid rats, FBN). Evoked responses were obtained by stimulating the main trunk of the SLN and recording the response using a 160‐μm cuff electrode placed around the iSLN. SNAP were averaged from 10 stimulations. Laryngeal adductor reflex (LAR) threshold measurements were obtained with stimulation of the iSLN and direct laryngoscopy. The sections of the iSLN were obtained for histologic analysis. Results SLN‐evoked responses were successfully obtained in 18 hemi‐laryngeal preparations (SD n = 13 and FBN n = 5) with corresponding LAR threshold measurements. Mean(±SD) SNAP latency, total duration, amplitude, negative durations, and intensity were 2.28 ms (±0.56), 2.13 ms (±0.70), 879 μV (±535), and 0.69 mA (±0.25), respectively. SLN stimulation threshold to elicit an LAR was of 0.84 mA (±0.31). Conclusion It is feasible to record evoked SLN responses in two adult rat strains. This work may lead to a tractable animal model for objective measurements of SLN neurophysiology with various disease states. Level of Evidence N/A Laryngoscope , 2024
Dam safety assessment is typically made by comparison between the outcome of some predictive model and measured monitoring data. This is done separately for each response variable, and the results ...are later interpreted before decision making. In this work, three approaches based on machine learning classifiers are evaluated for the joint analysis of a set of monitoring variables: multi-class, two-class and one-class classification. Support vector machines are applied to all prediction tasks, and random forest is also used for multi-class and two-class. The results show high accuracy for multi-class classification, although the approach has limitations for practical use. The performance in two-class classification is strongly dependent on the features of the anomalies to detect and their similarity to those used for model fitting. The one-class classification model based on support vector machines showed high prediction accuracy, while avoiding the need for correctly selecting and modelling the potential anomalies. A criterion for anomaly detection based on model predictions is defined, which results in a decrease in the misclassification rate. The possibilities and limitations of all three approaches for practical use are discussed.
Background
Anti‐SARS‐CoV‐2 S antibodies prevent viral replication. Critically ill COVID‐19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies ...influence survival and viral dissemination in ICU‐COVID patients is unknown.
Patients/Methods
We studied the impact of anti‐SARS‐CoV‐2 S antibodies levels on survival, viral RNA‐load in plasma, and N‐antigenaemia in 92 COVID‐19 patients over ICU admission.
Results
Frequency of N‐antigenaemia was >2.5‐fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA‐load in plasma, representing a protective factor against mortality (adjusted HR CI 95%, p): (S IgM AUC ≥ 60: 0.44 0.22; 0.88, 0.020); (S IgG AUC ≥ 237: 0.31 0.16; 0.61, <0.001). Viral RNA‐load in plasma and N‐antigenaemia predicted increased mortality: (N1‐viral load ≥2.156 copies/ml: 2.25 1.16; 4.36, 0.016); (N‐antigenaemia: 2.45 1.27; 4.69, 0.007).
Conclusions
Low anti‐SARS‐CoV‐2 S antibody levels predict mortality in critical COVID‐19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS‐CoV‐2.
The discrete element method (DEM) is well suited for calculating the behaviour of bulk materials. However, its application is limited because of the cumbersome calibration process required. Trial and ...error calibration can be useful for the computation of single outputs, but is unfeasible when the aim is reproducing more complex phenomena with high accuracy. This paper describes an iterative procedure based on machine learning to automatically calibrate the parameters of DEM models for reproducing the behaviour of bulk materials. The performance of the methodology is assessed by its application to the calibration of a DEM model to compute the stress–strain evolution of a cohesive material under uniaxial compression. In this case, a random forest model is used in conjunction with the iterative calibration algorithm proposed. The results of this study show that the algorithm is accurate and flexible for the calibration of material parameters.
ABSTRACT
Capillary malformation–arteriovenous malformation (CM–AVM) is an autosomal‐dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for ...fast‐flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM–AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM–AVM (n = 100), common CM(s) (port‐wine stain; n = 100), Sturge–Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty‐eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM–AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the “second‐hit” hypothesis as a pathophysiological mechanism for CM–AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild‐type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM–AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast‐flow lesions warrants careful clinical and radiologic examination, and regular follow‐up.
Capillary malformation‐arteriovenous malformation (CM‐AVM) is an autosomal‐dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast‐flow lesions. In this study we showed that RASA1 mutations are specifically identified in patients with CM‐AVM, in about 2/3 of them. The phenotypes and genotypes of 68 novel families are reported. This study expands the phenotypic spectrum to include zones of numerous small pale halos with central punctate red spots in the extremities.
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