This paper assesses trending AI foundation models, especially emerging computer vision foundation models and their performance in natural landscape feature segmentation. While the term foundation ...model has quickly garnered interest from the geospatial domain, its definition remains vague. Hence, this paper will first introduce AI foundation models and their defining characteristics. Built upon the tremendous success achieved by Large Language Models (LLMs) as the foundation models for language tasks, this paper discusses the challenges of building foundation models for geospatial artificial intelligence (GeoAI) vision tasks. To evaluate the performance of large AI vision models, especially Meta’s Segment Anything Model (SAM), we implemented different instance segmentation pipelines that minimize the changes to SAM to leverage its power as a foundation model. A series of prompt strategies were developed to test SAM’s performance regarding its theoretical upper bound of predictive accuracy, zero-shot performance, and domain adaptability through fine-tuning. The analysis used two permafrost feature datasets, ice-wedge polygons and retrogressive thaw slumps because (1) these landform features are more challenging to segment than man-made features due to their complicated formation mechanisms, diverse forms, and vague boundaries; (2) their presence and changes are important indicators for Arctic warming and climate change. The results show that although promising, SAM still has room for improvement to support AI-augmented terrain mapping. The spatial and domain generalizability of this finding is further validated using a more general dataset EuroCrops for agricultural field mapping. Finally, we discuss future research directions that strengthen SAM’s applicability in challenging geospatial domains.
Chlorarachniophytes are amoeboflagellate cercozoans that acquired a plastid by secondary endosymbiosis. Chlorarachniophytes are the last major group of algae for which there is no completely ...sequenced plastid genome. Here we describe the 69.2-kbp chloroplast genome of the model chlorarachniophyte Bigelowiella natans. The genome is highly reduced in size compared with plastids of other photosynthetic algae and is closer in size to genomes of several nonphotosynthetic plastids. Unlike nonphotosynthetic plastids, however, the B. natans chloroplast genome has not sustained a massive loss of genes, and it retains nearly all of the functional photosynthesis-related genes represented in the genomes of other green algae. Instead, the genome is highly compacted and gene dense. The genes are organized with a strong strand bias, and several unusual rearrangements and inversions also characterize the genome; notably, an inversion in the small-subunit rRNA gene, a translocation of 3 genes in the major ribosomal protein operon, and the fragmentation of the cluster encoding the large photosystem proteins PsaA and PsaB. The chloroplast endosymbiont is known to be a green alga, but its evolutionary origin and relationship to other primary and secondary green plastids has been much debated. A recent hypothesis proposes that the endosymbionts of chlorarachniophytes and euglenids share a common origin (the Cabozoa hypothesis). We inferred phylogenies using individual and concatenated gene sequences for all genes in the genome. Concatenated gene phylogenies show a relationship between the B. natans plastid and the ulvophyte-trebouxiophyte-chlorophyte clade of green algae to the exclusion of Euglena. The B. natans plastid is thus not closely related to that of Euglena, which suggests that plastids originated independently in these 2 groups and the Cabozoa hypothesis is false.
The establishment of the mitochondrion is seen as a transformational step in the origin of eukaryotes. With the mitochondrion came bioenergetic freedom to explore novel evolutionary space leading to ...the eukaryotic radiation known today. The tight integration of the bacterial endosymbiont with its archaeal host was accompanied by a massive endosymbiotic gene transfer resulting in a small mitochondrial genome which is just a ghost of the original incoming bacterial genome. This endosymbiotic gene transfer resulted in the loss of many genes, both from the bacterial symbiont as well the archaeal host. Loss of genes encoding redundant functions resulted in a replacement of the bulk of the host's metabolism for those originating from the endosymbiont. Glycolysis is one such metabolic pathway in which the original archaeal enzymes have been replaced by bacterial enzymes from the endosymbiont. Glycolysis is a major catabolic pathway that provides cellular energy from the breakdown of glucose. The glycolytic pathway of eukaryotes appears to be bacterial in origin, and in well-studied model eukaryotes it takes place in the cytosol. In contrast, here we demonstrate that the latter stages of glycolysis take place in the mitochondria of stramenopiles, a diverse and ecologically important lineage of eukaryotes. Although our work is based on a limited sample of stramenopiles, it leaves open the possibility that the mitochondrial targeting of glycolytic enzymes in stramenopiles might represent the ancestral state for eukaryotes.
Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, the duration and impact of these changes on outcome from TBI are ...unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of dietary fiber, are important signaling molecules in the microbiota gut-brain axis. We hypothesized that TBI would lead to a sustained reduction in SCFA producing bacteria, fecal SCFAs concentration, and administration of soluble SCFAs would improve functional outcome after TBI. Adult mice (
= 10) had the controlled cortical impact (CCI) model of TBI performed (6 m/sec, 2-mm depth, 50-msec dwell). Stool samples were collected serially until 28 days after CCI and analyzed for SCFA concentration by high-performance liquid chromatography-mass spectrometry/mass spectrometry and microbiome analyzed by 16S gene sequencing. In a separate experiment, mice (
= 10/group) were randomized 2 weeks before CCI to standard drinking water or water supplemented with the SCFAs acetate (67.5 mM), propionate (25.9 mM), and butyrate (40 mM). Morris water maze performance was assessed on post-injury Days 14-19. Alpha diversity remained stable until 72 h, at which point a decline in diversity was observed without recovery out to 28 days. The taxonomic composition of post-TBI fecal samples demonstrated depletion of bacteria from
,
, and
families, and enrichment of bacteria from the
family. Analysis from paired fecal samples revealed a reduction in total SCFAs at 24 h and 28 days after TBI. Acetate, the most abundant SCFA detected in the fecal samples, was reduced at 7 days and 28 days after TBI. SCFA administration improved spatial learning after TBI versus standard drinking water. In conclusion, TBI is associated with reduced richness and diversity of commensal microbiota in the gut and a reduction in SCFAs detected in stool. Supplementation of soluble SCFAs improves spatial learning after TBI.
Introduction
We have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor–gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium ...contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear.
Methods
Mice (male; C57Bl/6,
Villincre
/+;
Pgc1afl/fl
mice, and
Pgc1afl/fl
) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study.
Results
We demonstrate a significant depletion in the NAD+ levels within the intestinal epithelium of mice undergoing experimental colitis, as well as humans with ulcerative colitis. While we found no decrease in the levels of NAD+-synthesizing enzymes within the intestinal epithelium of mice undergoing experimental colitis, we did find an increase in the mRNA level, as well as the enzymatic activity, of the NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment of mice undergoing experimental colitis with an NAD+ precursor reduced the severity of colitis, restored mitochondrial function, and increased active PGC1α levels; however, NAD+ repletion did not benefit transgenic mice that lack PGC1α within the intestinal epithelium, suggesting that the therapeutic effects require an intact PGC1α axis.
Discussion
Our results emphasize the importance of PGC1α expression to both mitochondrial health and homeostasis within the intestinal epithelium and suggest a novel therapeutic approach for disease management. These findings also provide a mechanistic basis for clinical trials of nicotinamide riboside in IBD patients.
Despite extensive studies, many questions remain about what structural and energetic factors give rise to the remarkable energy transport efficiency of photosynthetic light-harvesting protein ...complexes, owing largely to the inability to synthetically control such factors in these natural systems. Herein, we demonstrate energy transfer within a biomimetic light-harvesting complex consisting of identical chromophores attached in a circular array to a protein scaffold derived from the tobacco mosaic virus coat protein. We confirm the capability of energy transport by observing ultrafast depolarization in transient absorption anisotropy measurements and a redshift in time-resolved emission spectra in these complexes. Modeling the system with kinetic Monte Carlo simulations recapitulates the observed anisotropy decays, suggesting an inter-site hopping rate as high as 1.6 ps–1. With these simulations, we identify static disorder in orientation, site energy, and degree of coupling as key remaining factors to control to achieve long-range energy transfer in these systems. We thereby establish this system as a highly promising, bottom-up model for studying long-range energy transfer in light-harvesting protein complexes.
Creating artificial systems that mimic and surpass those found in nature is one of the great challenges of modern science. In the context of photosynthetic light harvesting, the difficulty lies in ...attaining utmost control over the energetics, positions and relative orientations of chromophores in densely packed arrays to transfer electronic excitation energy to desired locations with high efficiency. Toward achieving this goal, we use a highly versatile biomimetic protein scaffold from the tobacco mosaic virus coat protein on which chromophores can be attached at precise locations via linkers of differing lengths and rigidities. We show that minor linker modifications, including switching chiral configurations and alkyl chain shortening, lead to significant lengthening of the ultrafast excited state dynamics of the system as the linkers are shortened and rigidified. Molecular dynamics simulations provide molecular-level detail over how the chromophore attachment orientations, positions, and distances from the protein surface lead to the observed trends in system dynamics. In particular, we find that short and rigid linkers are able to sandwich water molecules between chromophore and protein, leading to chromophore–water–protein supracomplexes with intricately coupled dynamics that are highly dependent on their local protein environment. In addition, cyclohexyl-based linkers are identified as ideal candidates to retain rotational correlations over several nanoseconds and thus lock relative chromophore orientations throughout the lifetime of an exciton. Combining linker engineering with judicious placement of chromophores on the hydrated protein scaffold to exploit different chromophore–bath couplings provides a clear and effective path to producing highly controllable artificial light-harvesting systems that can increasingly mimic their natural counterparts, thus aiding to elucidate natural photosynthetic mechanisms.
Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is the primary regulator of mitochondrial biogenesis and was recently found to be highly expressed within the intestinal ...epithelium. PGC1α is decreased in the intestinal epithelium of patients with inflammatory bowel disease, but its role in pathogenesis is uncertain. We now hypothesize that PGC1α protects against the development of colitis and helps to maintain the integrity of the intestinal barrier. We selectively deleted PGC1α from the intestinal epithelium of mice by breeding a PGC1αloxP/loxP mouse with a villin-cre mouse. Their progeny (PGC1αΔIEC mice) were subjected to 2% dextran sodium sulfate (DSS) colitis for 7 days. The SIRT1 agonist SRT1720 was used to enhance PGC1α activation in wild-type mice during DSS exposure. Mice lacking PGC1α within the intestinal epithelium were more susceptible to DSS colitis than their wild-type littermates. Pharmacologic activation of PGC1α successfully ameliorated disease and restored mitochondrial integrity. These findings suggest that a depletion of PGC1α in the intestinal epithelium contributes to inflammatory changes through a failure of mitochondrial structure and function as well as a breakdown of the intestinal barrier, which leads to increased bacterial translocation. PGC1α induction helps to maintain mitochondrial integrity, enhance intestinal barrier function, and decrease inflammation.
•Loss of Dnmt3a in mice with Kras-driven leukemias skews toward a myeloid phenotype.•Combined Dnmt3a knockout/Kras mutants quickly succumb to aggressive myeloid disease.•Dysregulation of cell cycle ...and MYC are associated with biallelic Dnmt3a deletion.•This is a robust model for investigating Ras/DNMT3A-mutant acute myeloid leukemia.
DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies, including acute myeloid leukemia. An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly comutated genes in myeloid malignancies, such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ERT2 murine model systems to study the effects of constitutively active KrasG12D-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO). Due to the rapid generation of diverse nonhematologic tumors appearing after tamoxifen induction, we employed a transplantation model. With pretransplant tamoxifen induction, most Kras mice died quickly of T-cell malignancies regardless of Dnmt3a status. Using posttransplant induction, we observed a dose-dependent effect of DNMT3A depletion that skewed the leukemic phenotype toward a myeloid lineage. Specifically, 64% of 3aKO/Kras mice had exclusively myeloid disease compared with 36% of 3aHet/Kras and only 13% of Kras mice. Here, 3aKO combined with Kras led to increased disease burden, multiorgan infiltration, and faster disease progression. DOT1L inhibition exerted profound antileukemic effects in malignant 3aKO/Kras cells, but not malignant cells with Kras mutation alone, consistent with the known sensitivity of DNMT3A-mutant leukemia to DOT1L inhibition. RNAseq from malignant myeloid cells revealed that biallelic Dnmt3a deletion was associated with loss of cell-cycle regulation, MYC activation, and TNF⍺ signaling. Overall, we developed a robust model system for mechanistic and preclinical investigations of acute myeloid leukemia with DNMT3A and Ras-pathway lesions.
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