AUTOMATED FIVE-AXIS TOOL PATH GENERATION BASED ON DYNAMIC ANALYSIS

Ph.DDOCTOR OF PHILOSOPH

CHD-CXR: a de-identified publicly available dataset of chest x-ray for congenital heart disease

Congenital heart disease is a prevalent birth defect, accounting for approximately one-third of major birth defects. The challenge lies in early detection, especially in underdeveloped medical regions where a shortage of specialized physicians often leads to oversight. While standardized chest x-rays can assist in diagnosis and treatment, their effectiveness is limited by subtle cardiac manifestations. However, the emergence of deep learning in computer vision has paved the way for detecting subtle changes in chest x-rays, such as lung vessel density, enabling the detection of congenital heart disease in children. This highlights the need for further investigation. The lack of expert-annotated, high-quality medical image datasets hinders the progress of medical image artificial intelligence. In response, we have released a dataset containing 828 DICOM chest x-ray files from children with diagnosed congenital heart disease, alongside corresponding cardiac ultrasound reports. This dataset emphasizes complex structural characteristics, facilitating the transition from machine learning to machine teaching in deep learning. To ascertain the dataset's applicability, we trained a preliminary model and achieved an area under the receiver operating characteristic curve (ROC 0.85). We provide detailed introductions and publicly available datasets at: https://www.kaggle.com/competitions/congenital-heart-disease

Insertion of an Esterase Gene into a Specific Locust Pathogen (Metarhizium acridum) Enables It to Infect Caterpillars

An enduring theme in pathogenic microbiology is poor understanding of the mechanisms of host specificity. Metarhizium is a cosmopolitan genus of invertebrate pathogens that contains generalist species with broad host ranges such as M. robertsii (formerly known as M. anisopliae var. anisopliae) as well as specialists such as the acridid-specific grasshopper pathogen M. acridum. During growth on caterpillar (Manduca sexta) cuticle, M. robertsii up-regulates a gene (Mest1) that is absent in M. acridum and most other fungi. Disrupting M. robertsii Mest1 reduced virulence and overexpression increased virulence to caterpillars (Galleria mellonella and M. sexta), while virulence to grasshoppers (Melanoplus femurrubrum) was unaffected. When Mest1 was transferred to M. acridum under control of its native M. robertsii promoter, the transformants killed and colonized caterpillars in a similar fashion to M. robertsii. MEST1 localized exclusively to lipid droplets in M. robertsii conidia and infection structures was up-regulated during nutrient deprivation and had esterase activity against lipids with short chain fatty acids. The mobilization of stored lipids was delayed in the Mest1 disruptant mutant. Overall, our results suggest that expression of Mest1 allows rapid hydrolysis of stored lipids, and promotes germination and infection structure formation by M. robertsii during nutrient deprivation and invasion, while Mest1 expression in M. acridum broadens its host range by bypassing the regulatory signals found on natural hosts that trigger the mobilization of endogenous nutrient reserves. This study suggests that speciation in an insect pathogen could potentially be driven by host shifts resulting from changes in a single gene

Genome Sequencing and Comparative Transcriptomics of the Model Entomopathogenic Fungi Metarhizium anisopliae and M. acridum

Metarhizium spp. are being used as environmentally friendly alternatives to chemical insecticides, as model systems for studying insect-fungus interactions, and as a resource of genes for biotechnology. We present a comparative analysis of the genome sequences of the broad-spectrum insect pathogen Metarhizium anisopliae and the acridid-specific M. acridum. Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens. Both M. anisopliae and M. acridum have a strikingly larger proportion of genes encoding secreted proteins than other fungi, while ∼30% of these have no functionally characterized homologs, suggesting hitherto unsuspected interactions between fungal pathogens and insects. The analysis of transposase genes provided evidence of repeat-induced point mutations occurring in M. acridum but not in M. anisopliae. With the help of pathogen-host interaction gene database, ∼16% of Metarhizium genes were identified that are similar to experimentally verified genes involved in pathogenicity in other fungi, particularly plant pathogens. However, relative to M. acridum, M. anisopliae has evolved with many expanded gene families of proteases, chitinases, cytochrome P450s, polyketide synthases, and nonribosomal peptide synthetases for cuticle-degradation, detoxification, and toxin biosynthesis that may facilitate its ability to adapt to heterogenous environments. Transcriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity. Of particular note, M. acridum transcribed distinct G-protein coupled receptors on cuticles from locusts (the natural hosts) and cockroaches, whereas M. anisopliae transcribed the same receptor on both hosts. This study will facilitate the identification of virulence genes and the development of improved biocontrol strains with customized properties

Regulatory Roles of Histone Modifications in Filamentous Fungal Pathogens

Filamentous fungal pathogens have evolved diverse strategies to infect a variety of hosts including plants and insects. The dynamic infection process requires rapid and fine-tuning regulation of fungal gene expression programs in response to the changing host environment and defenses. Therefore, transcriptional reprogramming of fungal pathogens is critical for fungal development and pathogenicity. Histone post-translational modification, one of the main mechanisms of epigenetic regulation, has been shown to play an important role in the regulation of gene expressions, and is involved in, e.g., fungal development, infection-related morphogenesis, environmental stress responses, biosynthesis of secondary metabolites, and pathogenicity. This review highlights recent findings and insights into regulatory mechanisms of histone methylation and acetylation in fungal development and pathogenicity, as well as their roles in modulating pathogenic fungi–host interactions

Self-limiting paratransgenesis.

Presently, the principal tools to combat malaria are restricted to killing the parasite in infected people and killing the mosquito vector to thwart transmission. While successful, these approaches are losing effectiveness in view of parasite resistance to drugs and mosquito resistance to insecticides. Clearly, new approaches to fight this deadly disease need to be developed. Recently, one such approach-engineering mosquito resident bacteria to secrete anti-parasite compounds-has proven in the laboratory to be highly effective. However, implementation of this strategy requires approval from regulators as it involves introduction of recombinant bacteria into the field. A frequent argument by regulators is that if something unexpectedly goes wrong after release, there must be a recall mechanism. This report addresses this concern. Previously we have shown that a Serratia bacterium isolated from a mosquito ovary is able to spread through mosquito populations and is amenable to be engineered to secrete anti-plasmodial compounds. We have introduced a plasmid into this bacterium that carries a fluorescent protein gene and show that when cultured in the laboratory, the plasmid is completely lost in about 130 bacterial generations. Importantly, when these bacteria were introduced into mosquitoes, the bacteria were transmitted from one generation to the next, but the plasmid was lost after three mosquito generations, rendering the bacteria non-recombinant (wild type). Furthermore, no evidence was obtained for horizontal transfer of the plasmid to other bacteria either in culture or in the mosquito. Prior to release, it is imperative to demonstrate that the genes that thwart parasite development in the mosquito are safe to the environment. This report describes a methodology to safely achieve this goal, utilizing transient expression from a plasmid that is gradually lost, returning the bacterium to wild type status

Functional zeta diversity can better reveal fish metacommunity assembly process in a transitional floodplain

Comprehending the mechanisms governing metacommunity assembly holds pivotal importance for effective conservation strategies. Amidst diverse theories in explaining metacommunity assembly processes, ecologists are progressively delving into the interplay between ecological stochasticity and determinism in shaping species assemblages. Given the ease of measurement, three null model-based methodologies have been widely employed to measure the stochastic and deterministic process, i.e., dispersal-niche continuum index (DNCI), elements of metacommunity structure (EMS), and zeta diversity calculations. However, it is still in doubt which approach can better detect the dominant ecological process governing metacommunity assembly. In this study, we concurrently utilized these three approaches to reveal the fish metacommunity assembly processes in a transitional floodplain among different habitats between high- and low-water levels. In general, our results recognized functional zeta diversity as indicative measurement in this study case since it uniquely unveiled the significant assembly transitions from stochasticity to determinism in response to water receding. Specifically, fish metacommunity in high-water periods was governed by stochastic processes, which can be ascribed to connectivity and easier dispersal in the flooding period. In contrast, the deterministic process shaped fish metacommunity in low-water phase since the stringent environmental loading enhance environmental filtering. This phenomenon is more pronounced in lotic habitats due to the more intricate environments there. It is worth noting that EMS and DNCI approaches showed blind response to this shift. In consequence, our findings advocate for favoring zeta diversity in resolving stochastic and deterministic contributions in governing metacommunity assembly. In addition, our findings also highlight the superiority of functional diversity over traditional taxonomic diversity, since we recorded a more reasonable metacommunity assembly process revealed by the functional group approach, which emphasizes the significance of incorporating functional traits in community ecology