Biological data are accumulating at a faster rate, but interpreting them still remains a problem. Classifying biological data into distinct groups is the first step in understanding them. Data ...classification in response to a certain treatment is an extremely important aspect for differentially expressed genes in making present/absent calls. Many feature selection algorithms have been developed including the support vector machine recursive feature elimination procedure (SVM-RFE) and its variants. Support vector machine RFEs are greedy methods that attempt to find superlative possible combinations leading to binary classification, which may not be biologically significant. To overcome this limitation of SVM-RFE, we propose a novel feature selection algorithm, termed as "sigFeature" (https://bioconductor.org/packages/sigFeature/), based on SVM and
statistic to discover the differentially significant features along with good performance in classification. The "sigFeature" R package is centered around a function called "sigFeature," which provides automatic selection of features for the binary classification. Using six publicly available microarray data sets (downloaded from Gene Expression Omnibus) with different biological attributes, we further compared the performance of "sigFeature" to three other feature selection algorithms. A small number of selected features (by "sigFeature") also show higher classification accuracy. For further downstream evaluation of its biological signature, we conducted gene set enrichment analysis with the selected features (genes) from "sigFeature" and compared it with the outputs of other algorithms. We observed that "sigFeature" is able to predict the signature of four out of six microarray data sets accurately, whereas the other algorithms predict less data set signatures. Thus, "sigFeature" is considerably better than related algorithms in discovering differentially significant features from microarray data sets.
The nucleation and growth of hydroxyapatite is closely associated with the extracellular matrix environment. Bovine serum albumin, collagen and polyvinyl alcohol were used to mimic the extracellular ...matrix. An attempt to understand the role of these matrices on the synthesis and function of hydroxyapatite has been made. XRD, FT-IR, XPS, TG-DTA, SEM and TEM confirmed the formation of hydroxyapatite synthesized by the biomimetic route. Further, the role of the organic matrix in controlling the nucleation and growth of hydroxyapatite particles at the nano level is understood by in-depth analysis of the XPS spectra. The in vitro release of the anti-cancer drug methotrexate in aqueous solution was studied, and the in vitro release profile was assayed by elution in phosphate buffered saline with pH 7.4 and pH 5 at 37 °C. The percentage of loading and release profiles of the drug were evaluated. The results show that the use of the matrix increased the drug release efficiency from 44.5% to 66% at pH 7.4 and 78% to 98.92% at pH 5. These results suggest that the synthesized hydroxyapatite can be used as a pH responsive vehicle for delivering drugs. Further, the release profile was predicted by the Higuchi and Peppas models. The results suggest that the release mechanism is governed by Fickian diffusion for the initial 8 h followed by anomalous transport for longer times. The cytocompatibility of the materials was evaluated by in vitro cytotoxicity tests. Both MTT and live/dead assay observations indicated that the material had no adverse impact on cell proliferation. The results imply that these composites are bioactive with good cytocompatibility. Although all the matrices showed good results, the one with polyvinyl alcohol exhibited higher biocompatibility and drug release efficiency. A plausible explanation is proposed for the enhanced drug delivery efficiency of these materials.
sp. are invasive groups of pathogens belonging to class Oomycetes. In order to contain and control them, a deep knowledge of their biology and infection strategy is imperative. With the availability ...of large-scale sequencing data, it has been possible to look directly into their genetic material and understand the strategies adopted by them for becoming successful pathogens. Here, we have studied the genomes of 128
species available publicly with reasonable quality. Our analysis reveals that the simple sequence repeats (SSRs) of all
sp. follow distinct isolate specific patterns. We further show that TG/CA dinucleotide repeats are far more abundant in
sp. than other classes of repeats. In case of tri- and tetranucleotide SSRs also, TG/CA-containing motifs always dominate over others. The GC content of the SSRs are stable without much variation across the isolates of
. Telomeric repeats of
follow a pattern of (TTTAGGG)
or (TTAGGGT)
rather than the canonical (TTAGGG)n. RxLR (arginine-any amino acid-leucine-arginine) motifs containing effectors diverge rapidly in
and do not show any core common group. The RxLR effectors of some
isolates have a tendency to form clusters with RxLRs from other species than within the same species. An analysis of the flanking intergenic distance clearly indicates a two-speed genome organization for all the
isolates. Apart from effectors and the transposons, a large number of other virulence genes such as carbohydrate-active enzymes (CAZymes), transcriptional regulators, signal transduction genes, ATP-binding cassette transporters (ABC), and ubiquitins are also present in the repeat-rich compartments. This indicates a rapid co-evolution of this powerful arsenal for successful pathogenicity. Whole genome duplication studies indicate that the pattern followed is more specific to a geographic location. To conclude, the large-scale genomic studies of
have thrown light on their adaptive evolution, which is largely guided by the localized host-mediated selection pressure.
Non-invasive renal signatures can help in serial monitoring of diabetic patients. We tested whether urinary exosomal (UE) microRNA (miR) analysis could non-invasively predict renal pathology in ...diabetic rats during the course of diabetes. Diabetes mellitus (DM) was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg body weight). Non-diabetic control (CTRL) rats were injected with vehicle. Insulin (INS) treatment (5U/d, s.c.) was provided to 50% of the DM rats. Urine samples were collected at weeks 3, 6, and 9 following injections and UE prepared. An increase in miR-451-5p and miR-16, observed by pilot small RNA sequencing of UE RNA, was confirmed by quantitative real-time polymerase chain reaction (qPCR) and selected for further study. Subsets of rats were euthanized after 3, 6, and 9 weeks of diabetes for renal pathology analysis, including determination of the tubulointerstitial fibrotic index (TFI) and glomerulosclerotic index (GI) scores. qPCR showed a substantial rise in miR-451-5p in UE from DM rats during the course of diabetes, with a significant rise (median fold change >1000) between 3 and 6 weeks. Moreover, UE miR-451-5p at 6 weeks predicted urine albumin at 9 weeks (r = 0.76). A delayed but significant rise was also observed for miR-16. In contrast, mean urine albumin only increased 21% between 3 and 6 weeks (non-significant rise), and renal TFI and GI were unchanged till 9 weeks. Renal expression of miR-451-5p and miR-16 (at 10 weeks) did not correlate with urine levels, and moreover, was negatively associated with indices of renal pathology (r≥-0.70, p = 0.005 for TFI and r≥-0.6, p≤0.02 for GI). Overall, a relative elevation in renal miR-451-5p and miR-16 in diabetes appeared protective against diabetes-induced kidney fibrosis; while UE miR-451-5p may hold prognostic value as an early and sensitive non-invasive indicator of renal disease.
The genome of the soybean pathogen Phytophthora sojae contains nearly 400 genes encoding candidate effector proteins carrying the host cell entry motif RXLR-dEER. Here, we report a broad survey of ...the transcription, variation, and functions of a large sample of the P. sojae candidate effectors. Forty-five (12%) effector genes showed high levels of polymorphism among P. sojae isolates and significant evidence for positive selection. Of 169 effectors tested, most could suppress programmed cell death triggered by BAX, effectors, and/or the PAMP INF1, while several triggered cell death themselves. Among the most strongly expressed effectors, one immediate-early class was highly expressed even prior to infection and was further induced 2- to 10-fold following infection. A second early class, including several that triggered cell death, was weakly expressed prior to infection but induced 20- to 120-fold during the first 12 h of infection. The most strongly expressed immediate-early effectors could suppress the cell death triggered by several early effectors, and most early effectors could suppress INF1-triggered cell death, suggesting the two classes of effectors may target different functional branches of the defense response. In support of this hypothesis, misexpression of key immediate-early and early effectors severely reduced the virulence of P. sojae transformants.
Pathogens secrete effector molecules that facilitate the infection of their hosts. A number of effectors identified in plant pathogenic Phytophthora species possess N-terminal motifs (RXLR-dEER) ...required for targeting these effectors into host cells. Here, we bioinformatically identify >370 candidate effector genes in each of the genomes of P. sojae and P. ramorum. A single superfamily, termed avirulence homolog (Avh) genes, accounts for most of the effectors. The Avh proteins show extensive sequence divergence but are all related and likely evolved from a common ancestor by rapid duplication and divergence. More than half of the Avh proteins contain conserved C-terminal motifs (termed W, Y, and L) that are usually arranged as a module that can be repeated up to eight times. The Avh genes belong to the most rapidly evolving part of the genome, and they are nearly always located at synteny breakpoints. The superfamily includes all experimentally identified oomycete effector and avirulence genes, and its rapid pace of evolution is consistent with a role for Avh proteins in interaction with plant hosts.
Cellular reprogramming in response to environmental stress involves alteration of gene expression, changes in the protein and metabolite profile for ensuring better stress management in plants. ...Similar to other plant species originating in tropical and sub-tropical areas, indica rice is highly sensitive to low temperature that adversely affects its growth and grain productivity. Substantial work has been done to understand cold induced changes in gene expression in rice plants. However, adequate information is not available for early gene expression, especially in indica variety. Therefore, a transcriptome profile was generated for cold shock treated seedlings of IR64 variety to identify early responsive genes.
The functional annotation of early DEGs shows enrichment of genes involved in altered membrane rigidity and electrolytic leakage, the onset of calcium signaling, ROS generation and activation of stress responsive transcription factors in IR64. Gene regulatory network suggests that cold shock induced Ca2+ signaling activates DREB/CBF pathway and other groups of transcription factors such as MYB, NAC and ZFP; for activating various cold-responsive genes. The analysis also indicates that cold induced signaling proteins like RLKs, RLCKs, CDPKs and MAPKK and ROS signaling proteins. Further, several late-embryogenesis-abundant (LEA), dehydrins and low temperature-induced-genes were upregulated under early cold shock condition, indicating the onset of water-deficit conditions. Expression profiling in different high yielding cultivars shows high expression of cold-responsive genes in Heera and CB1 indica varieties. These varieties show low levels of cold induced ROS production, electrolytic leakage and high germination rate post-cold stress, compared to IR36 and IR64. Collectively, these results suggest that these varieties may have improved adaptability to cold stress.
The results of this study provide insights about early responsive events in Oryza sativa l.ssp. indica cv IR64 in response to cold stress. Our data shows the onset of cold response is associated with upregulation of stress responsive TFs, hydrophilic proteins and signaling molecules, whereas, the genes coding for cellular biosynthetic enzymes, cell cycle control and growth-related TFs are downregulated. This study reports that the generation of ROS is integral to the early response to trigger the ROS mediated signaling events during later stages.
Processing of commercial bioactive glasses in the form of scaffolds, fibers and coatings on metal implants is a major challenge due to their high crystallization tendency leading to loss of many ...desirable functionalities relevant to bone tissue engineering applications. In this context, this work focuses on developing borosilicate bioactive glasses with improved thermal stability from the detailed understanding of composition–structure–property correlations. Structural studies through Raman and magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy revealed the formation of a highly crosslinked network rich in B–O–Si bonds facilitating enhanced thermal stability (> 150 °C) for 17.96–35.92 mol% B
2
O
3
containing glasses. These glasses also exhibit substantially improved in vitro biological properties such as biomineralization, cell proliferation, alkaline phosphatase (ALP) expression and antibacterial efficacy owing to predominance of B–O–Si and B–O–B bonds. However, more detailed data with pre-clinical studies are needed to confirm these observations, and for using them for specific applications.
Graphical abstract
The present study focuses on the stress response of a filamentous, AT-rich, heterocystous cyanobacterium
Mastigocladus laminosus
UU774, isolated from a hot spring, Taptapani, located in the eastern ...part of India. The genome of UU774 contains an indispensable fragment, scaffold_38, of unknown origin that is implicated during severe nitrogen and nutrition stress. Prolonged exposure to nitrogen compounds during starvation has profound adverse effects on UU774, leading to loss of mobility, loss of ability to fight pathogens, reduced cell division, decreased nitrogen-fixing ability, reduced ability to form biofilms, reduced photosynthetic and light-sensing ability, and reduced production of secreted effectors and chromosomal toxin genes, among others. Among genes showing extreme downregulation when grown in a medium supplemented with nitrogen with the fold change > 5 are transcriptional regulator gene WalR, carbonic anhydrases, RNA Polymerase Sigma F factor, fimbrial protein, and twitching mobility protein. The reduced expression of key enzymes involved in the uptake of phosphate and enzymes protecting oxygen-sensitive nitrogenases is significant during the presence of nitrogen. UU774 is presumed to withstand heat by overexpressing peptidases that may be degrading abnormally folded proteins produced during heat. The absence of a key gene responsible for heterocyst pattern formation, patS, and an aberrant hetN without a functional motif probably lead to the formation of a chaotic heterocyst pattern in UU774. We suggest that UU774 has diverged from
Fischerella
sp. PCC 9339, another hot spring species isolated in the United States.
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