Deep Chronnectome Learning via Full Bidirectional Long Short-Term Memory Networks for MCI Diagnosis

Brain functional connectivity (FC) extracted from resting-state fMRI (RS-fMRI) has become a popular approach for disease diagnosis, where discriminating subjects with mild cognitive impairment (MCI) from normal controls (NC) is still one of the most challenging problems. Dynamic functional connectivity (dFC), consisting of time-varying spatiotemporal dynamics, may characterize "chronnectome" diagnostic information for improving MCI classification. However, most of the current dFC studies are based on detecting discrete major brain status via spatial clustering, which ignores rich spatiotemporal dynamics contained in such chronnectome. We propose Deep Chronnectome Learning for exhaustively mining the comprehensive information, especially the hidden higher-level features, i.e., the dFC time series that may add critical diagnostic power for MCI classification. To this end, we devise a new Fully-connected Bidirectional Long Short-Term Memory Network (Full-BiLSTM) to effectively learn the periodic brain status changes using both past and future information for each brief time segment and then fuse them to form the final output. We have applied our method to a rigorously built large-scale multi-site database (i.e., with 164 data from NCs and 330 from MCIs, which can be further augmented by 25 folds). Our method outperforms other state-of-the-art approaches with an accuracy of 73.6% under solid cross-validations. We also made extensive comparisons among multiple variants of LSTM models. The results suggest high feasibility of our method with promising value also for other brain disorder diagnoses.Comment: The paper has been accepted by MICCAI201

Effects of elevated [CO2 ] on maize defence against mycotoxigenic Fusarium verticillioides.

Maize is by quantity the most important C4 cereal crop; however, future climate changes are expected to increase maize susceptibility to mycotoxigenic fungal pathogens and reduce productivity. While rising atmospheric [CO2 ] is a driving force behind the warmer temperatures and drought, which aggravate fungal disease and mycotoxin accumulation, our understanding of how elevated [CO2 ] will effect maize defences against such pathogens is limited. Here we report that elevated [CO2 ] increases maize susceptibility to Fusarium verticillioides proliferation, while mycotoxin levels are unaltered. Fumonisin production is not proportional to the increase in F. verticillioides biomass, and the amount of fumonisin produced per unit pathogen is reduced at elevated [CO2 ]. Following F. verticillioides stalk inoculation, the accumulation of sugars, free fatty acids, lipoxygenase (LOX) transcripts, phytohormones and downstream phytoalexins is dampened in maize grown at elevated [CO2 ]. The attenuation of maize 13-LOXs and jasmonic acid production correlates with reduced terpenoid phytoalexins and increased susceptibility. Furthermore, the attenuated induction of 9-LOXs, which have been suggested to stimulate mycotoxin biosynthesis, is consistent with reduced fumonisin per unit fungal biomass at elevated [CO2 ]. Our findings suggest that elevated [CO2 ] will compromise maize LOX-dependent signalling, which will influence the interactions between maize and mycotoxigenic fungi

Harmonic Force Constants for Molecular Mechanics Force Fields via Hessian Matrix Projection.

A modification to the Seminario method [ Int. J. Quantum Chem. 1996 , 60 , 1271 - 1277 ] is proposed, which derives accurate harmonic bond and angle molecular mechanics force field parameters directly from the quantum mechanical Hessian matrix. The new method reduces the average error in the reproduction of quantum mechanical normal-mode frequencies of a benchmark set of 70 molecules from 12.3% using the original method, to 6.3%. The modified Seminario method is fully automated, and all parameters are computed directly from quantum mechanical data, thereby avoiding interdependency between bond and angle parameters and other components of the force field. A complete set of bond and angle force field parameters for the 20 naturally occurring amino acids is also provided for use in the future development of protein force fields

First report of the ectomycorrhizal status of boletes on the Northern Yucatan Peninsula, Mexico determined using isotopic methods

Despite their prominent role for tree growth, few studies have examined the occurrence of ectomycorrhizal fungi in lowland, seasonally dry tropical forests (SDTF). Although fruiting bodies of boletes have been observed in a dry tropical forest on the Northern Yucatan Peninsula, Mexico, their occurrence is rare and their mycorrhizal status is uncertain. To determine the trophic status (mycorrhizal vs. saprotrophic) of these boletes, fruiting bodies were collected and isotopically compared to known saprotrophic fungi, foliage, and soil from the same site. Mean δ15N and δ13C values differed significantly between boletes and saprotrophic fungi, with boletes 8.0‰ enriched and 2.5‰ depleted in 15N and 13C, respectively relative to saprotrophic fungi. Foliage was depleted in 13C relative to both boletes and saprotrophic fungi. Foliar δ15N values, on the other hand, were similar to saprotrophic fungi, yet were considerably lower relative to bolete fruiting bodies. Results from this study provide the first isotopic evidence of ectomycorrhizal fungi in lowland SDTF and emphasize the need for further research to better understand the diversity and ecological importance of ectomycorrhizal fungi in these forested ecosystems

Genomic variation and biogeography of Antarctic haloarchaea

© 2018 The Author(s). Background: The genomes of halophilic archaea (haloarchaea) often comprise multiple replicons. Genomic variation in haloarchaea has been linked to viral infection pressure and, in the case of Antarctic communities, can be caused by intergenera gene exchange. To expand understanding of genome variation and biogeography of Antarctic haloarchaea, here we assessed genomic variation between two strains of Halorubrum lacusprofundi that were isolated from Antarctic hypersaline lakes from different regions (Vestfold Hills and Rauer Islands). To assess variation in haloarchaeal populations, including the presence of genomic islands, metagenomes from six hypersaline Antarctic lakes were characterised. Results: The sequence of the largest replicon of each Hrr. lacusprofundi strain (primary replicon) was highly conserved, while each of the strains' two smaller replicons (secondary replicons) were highly variable. Intergenera gene exchange was identified, including the sharing of a type I-B CRISPR system. Evaluation of infectivity of an Antarctic halovirus provided experimental evidence for the differential susceptibility of the strains, bolstering inferences that strain variation is important for modulating interactions with viruses. A relationship was found between genomic structuring and the location of variation within replicons and genomic islands, demonstrating that the way in which haloarchaea accommodate genomic variability relates to replicon structuring. Metagenome read and contig mapping and clustering and scaling analyses demonstrated biogeographical patterning of variation consistent with environment and distance effects. The metagenome data also demonstrated that specific haloarchaeal species dominated the hypersaline systems indicating they are endemic to Antarctica. Conclusion: The study describes how genomic variation manifests in Antarctic-lake haloarchaeal communities and provides the basis for future assessments of Antarctic regional and global biogeography of haloarchaea

Development and Validation of the Quantum Mechanical Bespoke Protein Force Field.

Molecular mechanics force field parameters for macromolecules, such as proteins, are traditionally fit to reproduce experimental properties of small molecules, and thus, they neglect system-specific polarization. In this paper, we introduce a complete protein force field that is designed to be compatible with the quantum mechanical bespoke (QUBE) force field by deriving nonbonded parameters directly from the electron density of the specific protein under study. The main backbone and sidechain protein torsional parameters are rederived in this work by fitting to quantum mechanical dihedral scans for compatibility with QUBE nonbonded parameters. Software is provided for the preparation of QUBE input files. The accuracy of the new force field, and the derived torsional parameters, is tested by comparing the conformational preferences of a range of peptides and proteins with experimental measurements. Accurate backbone and sidechain conformations are obtained in molecular dynamics simulations of dipeptides, with NMR J coupling errors comparable to the widely used OPLS force field. In simulations of five folded proteins, the secondary structure is generally retained, and the NMR J coupling errors are similar to standard transferable force fields, although some loss of the experimental structure is observed in certain regions of the proteins. With several avenues for further development, the use of system-specific nonbonded force field parameters is a promising approach for next-generation simulations of biological molecules

The flying buttress construct for posterior spinopelvic fixation: a technical note

<p>Abstract</p> <p>Background</p> <p>Posterior fusion of the spine to the pelvis in paediatric and adult spinal deformity is still challenging. Especially assembling of the posterior rod construct to the iliac screw is considered technically difficult. A variety of spinopelvic fixation techniques have been developed. However, extreme bending of the longitudinal rods or the use of 90-degree lateral offset connectors proved to be difficult, because the angle between the rod and the iliac screw varies from patient to patient.</p> <p>Methods</p> <p>We adopted a new spinopelvic fixation system, in which iliac screws are side-to-side connected to the posterior thoracolumbar rod construct, independent of the angle between the rod and the iliac screw. Open angled parallel connectors are used to connect short iliac rods from the posterior rod construct to the iliac screws at both sides. The construct resembles in form and function an architectural Flying Buttress, or lateral support arches, used in Gothic cathedrals.</p> <p>Results and discussion</p> <p>Three different cases that illustrate the Flying Buttress construct for spinopelvic fixation are reported here with the clinical details, radiographic findings and surgical technique used.</p> <p>Conclusion</p> <p>The Flying Buttress construct may offer an alternative surgical option for spinopelvic fixation in circumstances wherein coronal or sagittal balance cannot be achieved, for example in cases with significant residual pelvic obliquity, or in revision spinal surgery for failed lumbosacral fusion.</p

Unexpected host dependency of Antarctic Nanohaloarchaeota

In hypersaline environments, Nanohaloarchaeota (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaeota [DPANN] superphylum) are thought to be free-living microorganisms. We report cultivation of 2 strains of Antarctic Nanohaloarchaeota and show that they require the haloarchaeon Halorubrum lacusprofundi for growth. By performing growth using enrichments and fluorescence-activated cell sorting, we demonstrated successful cultivation of Candidatus Nanohaloarchaeum antarcticus, purification of Ca. Nha. antarcticus away from other species, and growth and verification of Ca. Nha. antarcticus with Hrr. lacusprofundi; these findings are analogous to those required for fulfilling Koch’s postulates. We use fluorescent in situ hybridization and transmission electron microscopy to assess cell structures and interactions; metagenomics to characterize enrichment taxa, generate metagenome assembled genomes, and interrogate Antarctic communities; and proteomics to assess metabolic pathways and speculate about the roles of certain proteins. Metagenome analysis indicates the presence of a single species, which is endemic to Antarctic hypersaline systems that support the growth of haloarchaea. The presence of unusually large proteins predicted to function in attachment and invasion of hosts plus the absence of key biosynthetic pathways (e.g., lipids) in metagenome assembled genomes of globally distributed Nanohaloarchaeota indicate that all members of the lineage have evolved as symbionts. Our work expands the range of archaeal symbiotic lifestyles and provides a genetically tractable model system for advancing understanding of the factors controlling microbial symbiotic relationships

An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints

In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the hard coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio