Giardia intestinalis is a globally important microbial pathogen with considerable public health, agricultural, and economic burden. Genome sequencing and comparative analyses have elucidated G. intestinalis to be a taxonomically diverse species consisting of at least eight different sub-types (assemblages A-H) that can infect a great variety of animal hosts, including humans. The best studied of these are assemblages A and B which have a broad host range and have zoonotic transmissibility towards humans where clinical Giardiasis can range from asymptomatic to diarrheal disease. Epidemiological surveys as well as previous molecular investigations have pointed towards critical genomic level differences within numerous molecular pathways and families of parasite virulence factors within assemblage A and B isolates. In this study, we explored the necessary machinery for the formation of vesicles and cargo transport in 89 Canadian isolates of assemblage A and B G. intestinalis. Considerable variability within the molecular complement of the endolysosomal ESCRT protein machinery, adaptor coat protein complexes, and ARF regulatory system have previously been reported. Here, we confirm inter-assemblage, but find no intra-assemblage variation within the trafficking systems examined. This variation includes losses of subunits belonging to the ESCRTIII as well as novel lineage specific duplications in components of the COPII machinery, ARF1, and ARFGEF families (BIG and CYTH). Since differences in disease manifestation between assemblages A and B have been controversially reported, our findings may well have clinical implications and even taxonomic, as the membrane trafficking system underpin parasite survival, pathogenesis, and propagation.
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http://dx.doi.org/10.1371/journal.pntd.0011837 | DOI Listing |
Sci Rep
December 2024
Department of General Surgery, Fuzong Clinical Medical College of Fujian Medical University, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China.
Glioma, the most prevalent primary intracranial malignancy among adults, is distinguished by its high morbidity and recurrence rates, posing a considerable threat to patients' quality of life and survival prospects. Consequently, the pursuit of efficacious molecular prognostic markers holds paramount importance. The exploration of the role of the KDELR3 kinase family in various neoplastic conditions constitutes an emerging area of research.
View Article and Find Full Text PDFStem Cells Transl Med
December 2024
NEI/OSCTRS/OGVFB, Bethesda, MD, United States.
Retinal pigment epithelium (RPE) atrophy is a significant cause of human blindness worldwide, occurring in polygenic diseases such as age-related macular degeneration (AMD) and monogenic diseases such as Stargardt diseases (STGD1) and late-onset retinal degeneration (L-ORD). The patient-induced pluripotent stem cells (iPSCs)-derived RPE (iRPE) model exhibits many advantages in understanding the cellular basis of pathological mechanisms of RPE atrophy. The iRPE model is based on iPSC-derived functionally mature and polarized RPE cells that reproduce several features of native RPE cells, such as phagocytosis of photoreceptor outer segments (POS) and replenishment of visual pigment.
View Article and Find Full Text PDFGut Microbes
December 2025
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Establishment of the gut microbiota during infancy is critical for host health with long-lasting implications. In this orchestrated process, microbial assembly is influenced by an increasing number of genetic and environmental factors, among which breastfeeding is considered as one of the most significant drivers for infant gut microbiota development. As the optimal diet for the infants, maternal milk provides numerous nutritional, microbial, and bioactive components to ensure the most adequate microbial growth and development of a 'healthy' gut microbiota during early life.
View Article and Find Full Text PDFPediatr Res
December 2024
Department of Neurological Surgery, Ohio State University Medical Center, Columbus, OH, USA.
Background: Post-hemorrhagic hydrocephalus (PHH) is a severe complication in premature infants following intraventricular hemorrhage (IVH). It is characterized by abnormal cerebrospinal fluid (CSF) accumulation, disrupted CSF dynamics, and elevated intracranial pressure (ICP), leading to significant neurological impairments.
Objective: This review provides an overview of recent molecular insights into the pathophysiology of PHH and evaluates emerging therapeutic approaches aimed at addressing its underlying mechanisms.
J Biol Chem
December 2024
Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, California, USA; Center for Molecular Biology of RNA, University of California, Santa Cruz, California, USA. Electronic address:
The spliceosome protein, SF3B1 associates with U2 snRNP during early spliceosome assembly for pre-mRNA splicing. Frequent somatic mutations in SF3B1 observed in cancer necessitates characterization of its role in identifying the branchpoint adenosine of introns. Remarkably, SF3B1 is the target of three distinct natural product drugs, each identified by their potent anti-tumor properties.
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