CATH 2024: CATH-AlphaFlow Doubles the Number of Structures in CATH and Reveals Nearly 200 New Folds.

CATH (https://www.cathdb.info) classifies domain structures from experimental protein structures in the PDB and predicted structures in the AlphaFold Database (AFDB). To cope with the scale of the predicted data a new NextFlow workflow (CATH-AlphaFlow), has been developed to classify high-quality domains into CATH superfamilies and identify novel fold groups and superfamilies. CATH-AlphaFlow uses a novel state-of-the-art structure-based domain boundary prediction method (ChainSaw) for identifying domains in multi-domain proteins. We applied CATH-AlphaFlow to process PDB structures not classified in CATH and AFDB structures from 21 model organisms, expanding CATH by over 100%. Domains not classified in existing CATH superfamilies or fold groups were used to seed novel folds, giving 253 new folds from PDB structures (September 2023 release) and 96 from AFDB structures of proteomes of 21 model organisms. Where possible, functional annotations were obtained using (i) predictions from publicly available methods (ii) annotations from structural relatives in AFDB/UniProt50. We also predicted functional sites and highly conserved residues. Some folds are associated with important functions such as photosynthetic acclimation (in flowering plants), iron permease activity (in fungi) and post-natal spermatogenesis (in mice). CATH-AlphaFlow will allow us to identify many more CATH relatives in the AFDB, further characterising the protein structure landscape.

Association of rodents with man-made infrastructures and food waste in Urban Singapore.

BACKGROUND: Rodent population control is an important measure in reducing the risk of rodent-borne disease transmission. In this study, we examined rodent activity in the sanitary waste network around the household waste-collection bin chamber of an urban residential apartment block. METHODS: We utilised infra-red camera traps to determine the pattern of rodent activity in a rodent-infested bin chamber and its associated sanitary waste network. Multivariable logistic regression was performed to assess the risk factors that were independently associated with rodent activity in the bin chambers. RESULT: The camera trap surveillance showed that the rodents were active in the bin chamber and sanitary network both in the day and at night. In the cross-sectional study, rodent activity in the bin chambers was independently associated with broken floor traps [Adjusted odds ratio (AOR): 36.7, CI: 21.3-66.3], calendar month [Log-likelihood ratio test (LRT) p = 0.002] and Town Council [LRT p = 0.004] variables. In restricted analysis, rodent activity in bin chambers was independently associated with defects in the wastewater pipe under the chamber [AOR: 12.3, CI: 4.3-51.7]. CONCLUSION: Our study suggests that urban municipal management councils should prioritize rodent control resources in areas according to the factors that increase the risk of rodent infestation.

CX3CL1 promotes lung cancer cell migration and invasion via the Src/focal adhesion kinase signaling pathway.

The present study investigated the role of C­X3­C motif chemokine ligand 1 (CX3CL1) in lung cancer cell migration and invasion and its potential mechanism. The expression levels of C­X3­C motif chemokine receptor 1 (CX3CR1) in six human lung cancer cell lines and one human bronchial epithelial cell line were assessed using reverse transcription­quantitative polymerase chain reaction and western blotting. Cell proliferation was assessed using the Cell Counting Kit­8 assay. Cell migration and invasion were examined using the Transwell assay, with and without Matrigel, respectively. The signaling pathway activated by CX3CL1 was analyzed via western blotting and inhibitory migration and invasion assays. CX3CR1 was expressed in the six lung cancer cell lines and one normal lung cell line. The lung cancer cell line, H460, was selected for further study. CX3CL1 did not significantly affect H460 proliferation; however, CX3CL1 did significantly enhance the migration and invasion of H460 cells. The Src/focal adhesion kinase (FAK) signaling pathway was activated in a time­dependent manner upon stimulation of CX3CL1. However, blocking Src activity with saracatinib prevented CX3CL1­mediated cell migration and invasion. Therefore, the findings indicated that CX3CL1 promotes lung cancer cell migration and invasion in vitro, and the Src/FAK signaling pathway serves a vital role in this process.

Wingless is a positive regulator of eyespot color patterns in Bicyclus anynana butterflies.

Eyespot patterns of nymphalid butterflies are an example of a novel trait yet, the developmental origin of eyespots is still not well understood. Several genes have been associated with eyespot development but few have been tested for function. One of these genes is the signaling ligand, wingless, which is expressed in the eyespot centers during early pupation and may function in eyespot signaling and color ring differentiation. Here we tested the function of wingless in wing and eyespot development by down-regulating it in transgenic Bicyclus anynana butterflies via RNAi driven by an inducible heat-shock promoter. Heat-shocks applied during larval and early pupal development led to significant decreases in wingless mRNA levels and to decreases in eyespot size and wing size in adult butterflies. We conclude that wingless is a positive regulator of eyespot and wing development in B. anynana butterflies.

Proton Magnetic Resonance Spectroscopy-Detected Changes of Marrow Fat Content in a Rabbit Model of Osteoporosis Treated With Epigallocatechin-3-Gallate.

OBJECTIVE: The aim of this study was to longitudinally evaluate the changes in marrow fat content of ovariectomized (OVX) rabbits treated with epigallocatechin-3-gallate (EGCG) using proton magnetic resonance spectroscopy (H-MRS). METHODS: Thirty-six female New Zealand rabbits were equally divided into sham operation, OVX controls, and OVX treated with EGCG (intraperitoneally, 1.8 mg/kg) for 5 months. Marrow fat fraction by H-MRS and bone density by peripheral quantitative computed tomography were determined at 0, 3, and 5 months. Serum biomarkers and marrow adipocytes were determined at the end of experiment. RESULTS: Estrogen deficiency increased marrow fat content in a time-dependent manner, with a variation of marrow fat fraction (FF) (+25.3%) at month 3 from baseline, and it was maintained until month 5 (+66.6%, all P < 0.001). In comparison with the sham-operated controls, adipocytes density, size, and percentage of adipocytes area in the OVX controls increased by 62.9%, 44.4%, and 178%, respectively (all P < 0.05). These OVX-induced pathological changes were partly reversed by EGCG treatment. In addition, EGCG treatment reduced bone turnover and increased bone density of OVX rabbits. CONCLUSIONS: Epigallocatechin-3-gallate exhibits an anabolic effect on osteoporotic bone by concomitantly rescuing bone mass and mitigating marrow adiposity. H-MRS appears to be a useful tool for monitoring osteoporosis-related treatments.