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Plant Physiology Jun 2024Plants must balance light capture for photosynthesis with protection from potentially harmful ultraviolet radiation (UV). Photoprotection is mediated by concerted action...
Plants must balance light capture for photosynthesis with protection from potentially harmful ultraviolet radiation (UV). Photoprotection is mediated by concerted action of photoreceptors, but the underlying molecular mechanisms are not fully understood. In this study, we provide evidence that UV RESISTANCE LOCUS 8 (UVR8) UV-B-, phytochrome red-, and cryptochrome blue-light photoreceptors converge on the induction of FERULIC ACID 5-HYDROXYLASE 1 (FAH1) that encodes a key enzyme in the phenylpropanoid biosynthesis pathway, leading to the accumulation of UV-absorbing sinapate esters in Arabidopsis (Arabidopsis thaliana). FAH1 induction depends on the bZIP transcription factors ELONGATED HYPOCOTYL 5 (HY5) and HY5-HOMOLOG (HYH) that function downstream of all three photoreceptors. Noticeably, mutants with hyperactive UVR8 signaling rescue fah1 UV sensitivity. Targeted metabolite profiling suggests that this phenotypic rescue is due to the accumulation of UV-absorbing metabolites derived from precursors of sinapate synthesis, namely coumaroyl-glucose and feruloyl-glucose. Our genetic dissection of the phenylpropanoid pathway combined with metabolomic and physiological analyses show that both sinapate esters and flavonoids contribute to photoprotection with sinapates playing a major role for UV screening. Our findings indicate that photoreceptor-mediated regulation of FAH1 and subsequent accumulation of sinapate "sunscreen" compounds is a key protective mechanism to mitigate damage, preserving photosynthetic performance, and ensuring plant survival under UV.
PubMed: 38918833
DOI: 10.1093/plphys/kiae352 -
Scientific Reports Jun 2024Early-life exposure to environmental toxicants like Benzo[a]pyrene (BaP) is associated with several health consequences in vertebrates (i.e., impaired or altered...
Early-life exposure to environmental toxicants like Benzo[a]pyrene (BaP) is associated with several health consequences in vertebrates (i.e., impaired or altered neurophysiological and behavioral development). Although toxicant impacts were initially studied relative to host physiology, recent studies suggest that the gut microbiome is a possible target and/or mediator of behavioral responses to chemical exposure in organisms, via the gut-brain axis. However, the connection between BaP exposure, gut microbiota, and developmental neurotoxicity remains understudied. Using a zebrafish model, we determined whether the gut microbiome influences BaP impacts on behavior development. Embryonic zebrafish were treated with increasing concentrations of BaP and allowed to grow to the larval life stage, during which they underwent behavioral testing and intestinal dissection for gut microbiome profiling via high-throughput sequencing. We found that exposure affected larval zebrafish microbiome diversity and composition in a manner tied to behavioral development: increasing concentrations of BaP were associated with increased taxonomic diversity, exposure was associated with unweighted UniFrac distance, and microbiome diversity and exposure predicted larval behavior. Further, a gnotobiotic zebrafish experiment clarified whether microbiome presence was associated with BaP exposure response and behavioral changes. We found that gut microbiome state altered the relationship between BaP exposure concentration and behavioral response. These results support the idea that the zebrafish gut microbiome is a determinant of the developmental neurotoxicity that results from chemical exposure.
Topics: Animals; Zebrafish; Benzo(a)pyrene; Gastrointestinal Microbiome; Behavior, Animal; Larva
PubMed: 38918492
DOI: 10.1038/s41598-024-65610-3 -
Nature Communications Jun 2024Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype...
Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype information and approximate pedigree structures. Here we use the approximate geographical locations of patients as a proxy for spatially correlated community-level environmental risk factors. We develop a spatial mixed linear effect (SMILE) model that incorporates both genetics and environmental contribution. We extract EHR and geographical locations from 257,620 nuclear families and compile 1083 disease outcome measurements from the MarketScan dataset. We augment the EHR with publicly available environmental data, including levels of particulate matter 2.5 (PM), nitrogen dioxide (NO), climate, and sociodemographic data. We refine the estimates of genetic heritability and quantify community-level environmental contributions. We also use wind speed and direction as instrumental variables to assess the causal effects of air pollution. In total, we find PM or NO have statistically significant causal effects on 135 diseases, including respiratory, musculoskeletal, digestive, metabolic, and sleep disorders, where PM and NO tend to affect biologically distinct disease categories. These analyses showcase several robust strategies for jointly modeling genetic and environmental effects on disease risk using large EHR datasets and will benefit upcoming biobank studies in the era of precision medicine.
Topics: Humans; Air Pollution; Particulate Matter; Nitrogen Dioxide; Risk Factors; Environmental Exposure; Male; Female; Electronic Health Records; Air Pollutants; Genetic Predisposition to Disease; Gene-Environment Interaction; Middle Aged; Adult
PubMed: 38918381
DOI: 10.1038/s41467-024-49566-6 -
Neotropical Entomology Jun 2024Mosquitoes (Diptera: Culicidae) pose a significant threat to public health worldwide, especially in tropical and subtropical regions, where they act as primary vectors...
Description of New Morphological Variation of Culex (Culex) coronator Dyar and Knab, 1906 and First Report of Culex (Carrollia) bonnei Dyar, 1921 Found in the Central Region of Peru.
Mosquitoes (Diptera: Culicidae) pose a significant threat to public health worldwide, especially in tropical and subtropical regions, where they act as primary vectors in transmission of infectious agents. In Peru, 182 culicid species have been identified and several species of the genus Culex are known to transmit arboviruses. However, knowledge of mosquito diversity and distribution remains limited, with many studies focusing on specific regions only. Here, we describe a new morphological variation of Cx. (Culex) coronator Dyar and Knab, 1906, and report the presence of Culex (Carrollia) bonnei Dyar, 1921 in the central region of Peru, Huanuco. Specimens were obtained through larvae collections and identified through morphologic characterization, including dissection of male genitalia, and molecular analyses. In total, 17 mosquitoes were analyzed, and the genitalia of the male specimens allowed the identification of Cx. coronator and Cx. bonnei. Partial sequences of the CoxI gene corresponding to these two species were obtained (N = 10). Phylogenetic analysis revealed that the sequences of Cx. coronator grouped in a monophyletic clade with sequences ascribed to other species corresponding to the subgenus Carrollia, while Cx. bonnei specimens formed a monophyletic clade with homologous sequences from GenBank. This study underscores the importance of continued efforts to study the diversity and distribution of mosquitoes in Peru, including their potential role as vectors of human pathogens, to underpin effective disease control and prevention strategies, highlighting the importance of a complemented morphological and molecular analysis.
PubMed: 38918340
DOI: 10.1007/s13744-024-01160-7 -
Acta Neuropathologica Jun 2024Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human...
Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APP mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator.
Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell (iPSC)-derived neurons carrying the familial AD APP mutation after cell injection into the mouse forebrain. APP mutant iPSCs and isogenic controls were differentiated into neurons revealing enhanced Aβ production, elevated phospho-tau, and impaired neurite outgrowth in APP neurons. Two months after transplantation, APP and control neural cells showed robust engraftment but at 12 months post-injection, APP grafts were smaller and demonstrated impaired neurite outgrowth compared to controls, while plaque and tangle pathology were not seen. Single-nucleus RNA-sequencing of micro-dissected grafts, performed 2 months after cell injection, identified significantly altered transcriptome signatures in APP iPSC-derived neurons pointing towards dysregulated synaptic function and axon guidance. Interestingly, APP neurons showed an increased expression of genes, many of which are also upregulated in postmortem neurons of AD patients including the transmembrane protein LINGO2. Downregulation of LINGO2 in cultured APP neurons rescued neurite outgrowth deficits and reversed key AD-associated transcriptional changes related but not limited to synaptic function, apoptosis and cellular senescence. These results provide important insights into transcriptional dysregulation in xenografted APP neurons linked to synaptic function, and they indicate that LINGO2 may represent a potential therapeutic target in AD.
Topics: Humans; Induced Pluripotent Stem Cells; Alzheimer Disease; Neurons; Transcriptome; Animals; Amyloid beta-Protein Precursor; Mice; Nerve Tissue Proteins; Mutation; Membrane Proteins; Synapses; Amyloid beta-Peptides; Signal Transduction
PubMed: 38918213
DOI: 10.1007/s00401-024-02755-5 -
The Journal of Neuroscience : the... Jun 2024The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control, serving as a significant source of synaptic input to the spinal cord....
The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control, serving as a significant source of synaptic input to the spinal cord. Experimental studies have shown that gene expression in individual VLM neurons is predictive of their function. However, the molecular and cellular organization of the VLM has remained uncertain. This study aimed to create a comprehensive dataset of VLM cells using single-cell RNA sequencing in male and female mice. The dataset was enriched with targeted sequencing of spinally-projecting and adrenergic/noradrenergic VLM neurons. Based on differentially expressed genes, the resulting dataset of 114,805 VLM cells identifies 23 subtypes of neurons, excluding those in the inferior olive, and 5 subtypes of astrocytes. Spinally-projecting neurons were found to be abundant in 7 subtypes of neurons, which were validated through in-situ hybridization. These subtypes included adrenergic/noradrenergic neurons, serotonergic neurons, and neurons expressing gene markers associated with pre-motor neurons in the ventromedial medulla. Further analysis of adrenergic/noradrenergic neurons and serotonergic neurons identified 9 and 6 subtypes, respectively, within each class of monoaminergic neurons. Marker genes that identify the neural network responsible for breathing were concentrated in 2 subtypes of neurons, delineated from each other by markers for excitatory and inhibitory neurons. These datasets are available for public download and for analysis with a user-friendly interface. Collectively, this study provides a fine-scale molecular identification of cells in the VLM, forming the foundation for a better understanding of the VLM's role in vital functions and motor control. The ventrolateral medulla (VLM) is an anatomically complex region of the brain that plays a crucial role in regulating vital functions, including autonomic and respiratory control, sleep-wake behaviors, cranial motor functions, and locomotion. This study comprehensively classifies VLM cell types and neuronal subtypes based on their molecular and anatomical features, by leveraging single-nuclei RNA sequencing, RNA fluorescence in situ hybridization, and axonal tract tracing. We present a dataset comprising 114,805 single-nuclei transcriptomes that identifies and validates the precise molecular characteristics of neurons involved in autonomic and motor systems functions. This publicly-available dataset offers new opportunities for comprehensive experimental studies to dissect the central organization of vital homeostatic functions and body movement.
PubMed: 38918066
DOI: 10.1523/JNEUROSCI.2211-23.2024 -
The Korean Journal of Gastroenterology... Jun 2024This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent...
This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent dysphagia. The cause was initially diagnosed as a 10 cm pedunculated lesion extending from the upper esophageal sphincter to the mid-esophagus. An ESD was chosen over traditional surgery because it is less invasive. The procedure involved a precise submucosal injection and excision with special techniques to manage bleeding from a central vessel. Despite the extraction challenges owing to the size of the lesion, it was successfully removed orally. A histopathological examination of the 8.3×4.2×2.3 cm specimen revealed the characteristic features of a well-differentiated liposarcoma, including MDM2 and CDK4 positivity. The follow-up revealed no recurrence, and active surveillance has been performed since. This report highlights the versatility of ESD in treating significant esophageal tumors and provides evidence for its efficacy as a minimally invasive alternative.
Topics: Humans; Male; Esophageal Neoplasms; Middle Aged; Endoscopic Mucosal Resection; Liposarcoma; Tomography, X-Ray Computed; Cyclin-Dependent Kinase 4; Proto-Oncogene Proteins c-mdm2; Esophagoscopy
PubMed: 38918037
DOI: 10.4166/kjg.2024.047 -
Endoscopy Dec 2024
Topics: Humans; Endoscopic Mucosal Resection; Rectal Neoplasms; Hemangioma, Cavernous; Male; Female; Middle Aged
PubMed: 38917982
DOI: 10.1055/a-2340-8794 -
Endoscopy Dec 2024
Topics: Humans; Neurofibromatosis 1; Endoscopic Mucosal Resection; Esophageal Neoplasms; Male; Female; Middle Aged
PubMed: 38917974
DOI: 10.1055/a-2321-9697 -
Endoscopy Dec 2024
Topics: Humans; Endoscopic Mucosal Resection; Stomach Neoplasms; Gastric Mucosa; Surgical Instruments; Male; Female; Aged; Middle Aged
PubMed: 38917972
DOI: 10.1055/a-2334-1103