• Deep learning for early detection of pathological changes in X-ray bone microstructures: case of osteoarthritis

      Jakaite, Livija; Schetinin, Vitaly; Hladůvka, Jiří; Minaev, Sergey; Ambia, Aziz; Krzanowski, Wojtek; ; University of Bedfordshire; TU Wien; Stavropol State Medical University; et al. (Nature, 2021-01-27)
      Texture features are designed to quantitatively evaluate patterns of spatial distribution of image pixels for purposes of image analysis and interpretation. Unexplained variations in the texture patterns often lead to misinterpretation and undesirable consequences in medical image analysis. In this paper we explore the ability of machine learning (ML) methods to design a radiology test of Osteoarthritis (OA) at early stage when the number of patients’ cases is small. In our experiments we use high-resolution X-ray images of knees in patients which were identified with Kellgren–Lawrence scores progressing from 1. The existing ML methods have provided a limited diagnostic accuracy, whilst the proposed Group Method of Data Handling strategy of Deep Learning has significantly extended the diagnostic test. The comparative experiments demonstrate that the proposed framework using the Zernike-based texture features has significantly improved the diagnostic accuracy on average by 11%. This allows us to conclude that the designed model for early diagnostic of OA will provide more accurate radiology tests, although new study is required when a large number of patients’ cases will be available.
    • The genome and transcriptome of Trichormus sp NMC-1: insights into adaptation to extreme environments on the Qinghai-Tibet Plateau

      Qiao, Qin; Huang, Yanyan; Qi, Ji.; Qu, Mingzhi; Jiang, Chen; Lin, Pengcheng; Li, Renhui; Song, Lirong; Yonezawa, Takahiro; Hasegawa, Masami; et al. (NATURE PUBLISHING GROUP, 2016-07-06)
      The Qinghai-Tibet Plateau (QTP) has the highest biodiversity for an extreme environment worldwide, and provides an ideal natural laboratory to study adaptive evolution. In this study, we generated a draft genome sequence of cyanobacteria Trichormus sp. NMC-1 in the QTP and performed whole transcriptome sequencing under low temperature to investigate the genetic mechanism by which T. sp. NMC-1 adapted to the specific environment. Its genome sequence was 5.9 Mb with a G+C content of 39.2% and encompassed a total of 5362 CDS. A phylogenomic tree indicated that this strain belongs to the Trichormus and Anabaena cluster. Genome comparison between T. sp. NMC-1 and six relatives showed that functionally unknown genes occupied a much higher proportion (28.12%) of the T. sp. NMC-1 genome. In addition, functions of specific, significant positively selected, expanded orthogroups, and differentially expressed genes involved in signal transduction, cell wall/membrane biogenesis, secondary metabolite biosynthesis, and energy production and conversion were analyzed to elucidate specific adaptation traits. Further analyses showed that the CheY-like genes, extracellular polysaccharide and mycosporine-like amino acids might play major roles in adaptation to harsh environments. Our findings indicate that sophisticated genetic mechanisms are involved in cyanobacterial adaptation to the extreme environment of the QTP.
    • Goat and buffalo milk fat globule membranes exhibit better effects at inducing apoptosis and reduction the viability of HT-29 cells

      Ji, Xiaoxi; Xu, Weili; Cui, Jie; Ma, Ying; Zhou, Shaobo (Nature Publishing Group, 2019-02-22)
      Bovine milk fat globule membrane (MFGM) has shown many health benefits, however, there has not been much study on non-cattle MFGMs. The purpose of this study was to compare the anti-proliferation effects and investigate the mechanisms of MFGMs from bovine, goat, buffalo, yak and camel milk in HT-29 cells. Results showed that protein content in MFGM of yak milk is the highest among five MFGM. All MFGMs inhibited cellular proliferation which was in agreement with cell morphology and apoptosis. However, the number of cells in S-phase from 24 h to 72 h was increased significantly by treatment with goat, buffalo and bovine MFGMs (100 μg/mL), but not yak and camel. All MFGMs treatment significantly reduced the mitochondrial membrane potential (with an order of goat>buffalo>bovine>camel>yak) and Bcl-2 expression, but increased the expression of both Bax and Caspase-3. Taken together, the results indicate that all MFGMs, especially goat and buffalo MFGMs, showed better effects at inducing apoptosis and inhibition of the proliferation of HT-29 cells. The mechanism might be arresting the cell cycle at S phase, depolarization of mitochondrial membrane potential, down-regulation of Bcl-2 expression and increase of Bax and Caspase-3 expression.
    • The intrinsically disordered Tarp protein from chlamydia binds actin with a partially preformed helix

      Tolchard, James; Walpole, Samuel J.; Miles, Andrew J.; Maytum, Robin; Eaglen, Lawrence A.; Hackstadt, Ted; Wallace, B.A.; Blumenschein, Tharin M.A. (Nature, 2018-01-31)
      Tarp (translocated actin recruiting phosphoprotein) is an effector protein common to all chlamydial species that functions to remodel the host-actin cytoskeleton during the initial stage of infection. In C. trachomatis, direct binding to actin monomers has been broadly mapped to a 100-residue region (726-825) which is predicted to be predominantly disordered, with the exception of a ~10-residue α-helical patch homologous to other WH2 actin-binding motifs. Biophysical investigations demonstrate that a Tarp726-825 construct behaves as a typical intrinsically disordered protein; within it, NMR relaxation measurements and chemical shift analysis identify the ten residue WH2-homologous region to exhibit partial α-helix formation. Isothermal titration calorimetry experiments on the same construct in the presence of monomeric G-actin show a well defined binding event with a 1:1 stoichiometry and Kd of 102 nM, whilst synchrotron radiation circular dichroism spectroscopy suggests the binding is concomitant with an increase in helical secondary structure. Furthermore, NMR experiments in the presence of G-actin indicate this interaction affects the proposed WH2-like α-helical region, supporting results from in silico docking calculations which suggest that, when folded, this α-helix binds within the actin hydrophobic cleft as seen for other actin-associated proteins.
    • A new family of periplasmic-binding proteins that sense arsenic oxyanions

      Badilla, Consuelo; Osborne, Thomas H.; Cole, Ambrose; Watson, Cameron; Djordjevic, Snezana; Santini, Joanne M. (SpringerNature, 2018-04-19)
      Arsenic contamination of drinking water affects more than 140 million people worldwide. While toxic to humans, inorganic forms of arsenic (arsenite and arsenate), can be used as energy sources for microbial respiration. AioX and its orthologues (ArxX and ArrX) represent the first members of a new sub-family of periplasmic-binding proteins that serve as the first component of a signal transduction system, that’s role is to positively regulate expression of arsenic metabolism enzymes. As determined by X-ray crystallography for AioX, arsenite binding only requires subtle conformational changes in protein structure, providing insights into protein-ligand interactions. The binding pocket of all orthologues is conserved but this alone is not sufficient for oxyanion selectivity, with proteins selectively binding either arsenite or arsenate. Phylogenetic evidence, clearly demonstrates that the regulatory proteins evolved together early in prokaryotic evolution and had a separate origin from the metabolic enzymes whose expression they regulate.
    • Plastid phylogenomics resolves ambiguous relationships within the orchid family and provides a solid timeframe for biogeography and macroevolution

      Serna-Sánchez, Maria Alejandra; Pérez-Escobar, Oscar A.; Bogarín, Diego; Torres-Jimenez, María Fernanda; Alvarez-Yela, Astrid Catalina; Arcila-Galvis, Juliana E.; Hall, Climbie F.; de Barros, Fábio; Pinheiro, Fábio; Dodsworth, Steven; et al. (SpringerNature, 2021-03-25)
      Recent phylogenomic analyses based on the maternally inherited plastid organelle have enlightened evolutionary relationships between the subfamilies of Orchidaceae and most of the tribes. However, uncertainty remains within several subtribes and genera for which phylogenetic relationships have not ever been tested in a phylogenomic context. To address these knowledge-gaps, we here provide the most extensively sampled analysis of the orchid family to date, based on 78 plastid coding genes representing 264 species, 117 genera, 18 tribes and 28 subtribes. Divergence times are also provided as inferred from strict and relaxed molecular clocks and birth-death tree models. Our taxon sampling includes 51 newly sequenced plastid genomes produced by a genome skimming approach. We focus our sampling efforts on previously unplaced clades within tribes Cymbidieae and Epidendreae. Our results confirmed phylogenetic relationships in Orchidaceae as recovered in previous studies, most of which were recovered with maximum support (209 of the 262 tree branches). We provide for the first time a clear phylogenetic placement for Codonorchideae within subfamily Orchidoideae, and Podochilieae and Collabieae within subfamily Epidendroideae. We also identify relationships that have been persistently problematic across multiple studies, regardless of the different details of sampling and genomic datasets used for phylogenetic reconstructions. Our study provides an expanded, robust temporal phylogenomic framework of the Orchidaceae that paves the way for biogeographical and macroevolutionary studies.