Cellular Information Processing Research Articles

Leptin Is Associated with Testosterone, Nutritional Markers, and Vascular Muscular Dysfunction in Chronic Kidney Disease.

Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages (p < 0.001) and also in HD (p = 0.026), with adipose tissue mass in pre-dialysis stages (p < 0.001), and also in HD (p < 0.001). In women HD patients, leptin correlated with NMD (p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein (p = 0.007; r = 0.28) and parathormone (p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.

Emergence of information processing in biological systems and the origin of life

ABSTRACT As every life form is composed of cells, elements of consciousness, namely memory and sentience, must be grounded in mechanisms that are integral to unicellular organisms. Earlier studies indicated that cellular cytoskeletal structures consisting of excitable, flexible, and oscillating polymers such as microtubules, along with quantum events, are potentially responsible for information processing and thus consciousness. This work attempts to solve the unknown, that is, how, at the spark of life, the phenomenon of cellular information processing first appears. This study posits that the spatially distributed wave energy of the molecules of an incepting cell interacts with space and generates a rotating bioinformation field, forming a vortex. This vortex, the local energy maximum, whose inbound and outbound energy fluxes represent signal reception and dispersal, is a critical step in the spark of life responsible for information storage, and with incremental wave superpositions, exhibits information processing. The vorticity of the rotating field is computed, and the obtained field characteristics indicated the emergence of a prebiotic complex to initiate information processing. Furthermore, the developed system model explains how perturbations from the environment are converted into response signals for the emanation of sense, locomotion, nutrition, and asexual reproduction, the fundamental evolutionary building blocks of prokaryotes. Further research directions include explaining how the energy potential available in the bio-information field and the vortex leads to the first formation of genetic material, emergence of cytoskeleton, and extension of bio-information field to multi-cellular organisms.

D-SPIN constructs gene regulatory network models from multiplexed scRNA-seq data revealing organizing principles of cellular perturbation response.

Gene regulatory networks within cells modulate the expression of the genome in response to signals and changing environmental conditions. Reconstructions of gene regulatory networks can reveal the information processing and control principles used by cells to maintain homeostasis and execute cell-state transitions. Here, we introduce a computational framework, D-SPIN, that generates quantitative models of gene regulatory networks from single-cell mRNA-seq datasets collected across thousands of distinct perturbation conditions. D-SPIN models the cell as a collection of interacting gene-expression programs, and constructs a probabilistic model to infer regulatory interactions between gene-expression programs and external perturbations. Using large Perturb-seq and drug-response datasets, we demonstrate that D-SPIN models reveal the organization of cellular pathways, sub-functions of macromolecular complexes, and the logic of cellular regulation of transcription, translation, metabolism, and protein degradation in response to gene knockdown perturbations. D-SPIN can also be applied to dissect drug response mechanisms in heterogeneous cell populations, elucidating how combinations of immunomodulatory drugs can induce novel cell states through additive recruitment of gene expression programs. D-SPIN provides a computational framework for constructing interpretable models of gene-regulatory networks to reveal principles of cellular information processing and physiological control.

The Hill function is the universal Hopfield barrier for sharpness of input–output responses

The Hill functions, [Formula: see text], have been widely used in biology for over a century but, with the exception of [Formula: see text], they have had no justification other than as a convenient fit to empirical data. Here, we show that they are the universal limit for the sharpness of any input-output response arising from a Markov process model at thermodynamic equilibrium. Models may represent arbitrary molecular complexity, with multiple ligands, internal states, conformations, coregulators, etc, under core assumptions that are detailed in the paper. The model output may be any linear combination of steady-state probabilities, with components other than the chosen input ligand held constant. This formulation generalizes most of the responses in the literature. We use a coarse-graining method in the graph-theoretic linear framework to show that two sharpness measures for input-output responses fall within an effectively bounded region of the positive quadrant, [Formula: see text], for any equilibrium model with [Formula: see text] input binding sites. [Formula: see text] exhibits a cusp which approaches, but never exceeds, the sharpness of [Formula: see text], but the region and the cusp can be exceeded when models are taken away from thermodynamic equilibrium. Such fundamental thermodynamic limits are called Hopfield barriers, and our results provide a biophysical justification for the Hill functions as the universal Hopfield barriers for sharpness. Our results also introduce an object, [Formula: see text], whose structure may be of mathematical interest, and suggest the importance of characterizing Hopfield barriers for other forms of cellular information processing.

The previously uncharacterized RnpM (YlxR) protein modulates the activity of ribonuclease P in Bacillus subtilis in vitro.

Even though Bacillus subtilis is one of the most studied organisms, no function has been identified for about 20% of its proteins. Among these unknown proteins are several RNA- and ribosome-binding proteins suggesting that they exert functions in cellular information processing. In this work, we have investigated the RNA-binding protein YlxR. This protein is widely conserved in bacteria and strongly constitutively expressed in B. subtilis suggesting an important function. We have identified the RNA subunit of the essential RNase P as the binding partner of YlxR. The main activity of RNase P is the processing of 5' ends of pre-tRNAs. In vitro processing assays demonstrated that the presence of YlxR results in reduced RNase P activity. Chemical cross-linking studies followed by in silico docking analysis and experiments with site-directed mutant proteins suggest that YlxR binds to the region of the RNase P RNA that is important for binding and cleavage of the pre-tRNA substrate. We conclude that the YlxR protein is a novel interaction partner of the RNA subunit of RNase P that serves to finetune RNase P activity to ensure appropriate amounts of mature tRNAs for translation. We rename the YlxR protein RnpM for RNase P modulator.

Dissecting the biophysics and biology of intrinsically disordered proteins

Intrinsically disordered regions (IDRs) within human proteins play critical roles in cellular information processing, including signaling, transcription, stress response, DNA repair, genome organization, and RNA processing. Here, we summarize current challenges in the field and propose cutting-edge approaches to address them in physiology and disease processes, with a focus on cancer.

Complex Synaptic and Intrinsic Interactions Disrupt Input/Output Functions in the Hippocampus of Scn1b Knock-Out Mice.

Pathogenic variants in SCN1B have been linked to severe developmental epileptic encephalopathies including Dravet syndrome. Scn1b knock-out (KO) mice model SCN1B loss-of-function (LOF) disorders, demonstrating seizures, developmental delays, and early death. SCN1B encodes the protein β1, an ion channel auxiliary subunit that also has roles in cell adhesion, neurite outgrowth, and gene expression. The goal of this project is to better understand of how loss of Scn1b alters information processing in the brain, resulting in seizures and associated cognitive dysfunction. Using slice electrophysiology in the CA1 region of the hippocampus from male and female Scn1b KO mice and wild-type (WT) littermates, we found that processing of physiologically relevant patterned Schaffer collateral (SC) stimulation produces larger, prolonged depolarizations and increased spiking in KO neurons compared with WTs. KO neurons exhibit enhanced intrinsic excitability, firing more action potentials with current injection. Interestingly, SC stimulation produces smaller, more facilitating excitatory and IPSCs in KO pyramidal neurons, but larger postsynaptic potentials (PSPs) with the same stimulation. We also found reduced intrinsic firing of parvalbumin (PV)-expressing interneurons and disrupted recruitment of both parvalbumin-expressing and somatostatin (SST)-expressing interneurons in response to patterned synaptic stimulation. Neuronal information processing relies on the interplay between synaptic properties, intrinsic properties that amplify or suppress incoming synaptic signals, and firing properties that produce cellular output. We found changes at each of these levels in Scn1b KO pyramidal neurons, resulting in fundamentally altered cellular information processing in the hippocampus that likely contributes to the complex phenotypes of SCN1B-linked epileptic encephalopathies.SIGNIFICANCE STATEMENT Genetic developmental epileptic encephalopathies have limited treatment options, in part because of our lack of understanding of how genetic changes result in dysfunction at the cellular and circuit levels. SCN1B is a gene linked to Dravet syndrome and other developmental epileptic encephalopathies, and Scn1b knock-out (KO) mice phenocopy the human disease, allowing us to study underlying neurophysiological changes. Here, we found changes at all levels of neuronal information processing in brains lacking Scn1b, including intrinsic excitability, synaptic properties, and synaptic integration, resulting in greatly enhanced input/output functions of the hippocampus. Our study shows that loss of Scn1b results in a complex array of cellular and network changes that fundamentally alters information processing in the hippocampus.

A revised central dogma for the 21st century: All biology is cognitive information processing

Crick's Central Dogma has been a foundational aspect of 20th century biology, describing an implicit relationship governing the flow of information in biological systems in biomolecular terms. Accumulating scientific discoveries support the need for a revised Central Dogma to buttress evolutionary biology's still-fledgling migration from a Neodarwinian canon. A reformulated Central Dogma to meet contemporary biology is proposed: all biology is cognitive information processing. Central to this contention is the recognition that life is the self-referential state, instantiated within the cellular form. Self-referential cells act to sustain themselves and to do so, cells must be in consistent harmony with their environment. That consonance is achieved by the continuous assimilation of environmental cues and stresses as information to self-referential observers. All received cellular information must be analyzed to be deployed as cellular problem-solving to maintain homeorhetic equipoise. However, the effective implementation of information is definitively a function of orderly information management. Consequently, effective cellular problem-solving is information processing and management. The epicenter of that cellular information processing is its self-referential internal measurement. All further biological self-organization initiates from this obligate activity. As the internal measurement by cells of information is self-referential by definition, self-reference is biological self-organization, underpinning 21st century Cognition-Based Biology.

Dissipation kinetics of chlorpyrifos and 3,5,6 trichloro-2-pyridinol under vegetation of different aromatic grasses: Linkage with enzyme kinetics and microbial community of soil

The dissipation of chlorpyrifos (CP) and its hydrolytic metabolite 3,5,6-trichloro-2-pyridinol (TCP) in the soil is crucial for safe agriculture. However, there is still lacking relevant information about its dissipation under different vegetation for remediation purposes. In the present study, evaluation of dissipation of CP and TCP in non-planted and planted soil with different cultivars of three types of aromatic grass viz Cymbopogon martinii (Roxb. Wats), Cymbopogon flexuosus, and Chrysopogon zizaniodes (L.) Nash was examined in light of soil enzyme kinetics, microbial communities, and root exudation. Results revealed that the dissipation of CP was well-fitted into a single first-order exponential model (SFO). A significant reduction in the half-life (DT50) of CP was observed in planted soil (30–63 days) than in non-planted soil (95 days). The presence of TCP in all soil samples was observed. The three types of the inhibitory effect of CP i.e. linear mixed inhibition (increase in enzyme-substrate affinity (Km) and decrease in enzyme pool (Vmax), un-competitive inhibition (decrease in Km and Vmax), and simple competitive inhibition were observed on soil enzymes involved in mineralization of carbon, nitrogen, phosphorus, and sulfur. The improvement in the enzyme pool (Vmax) was observed in planted soil. Streptomyces, Clostridium, Kaistobacter, Planctomyces, and Bacillus were the dominant genera in CP stress soil. CP contamination in soil demonstrated a reduction of richness in microbial diversity and enhancement of functional gene family related to cellular process, metabolism, genetic, and environmental information processing. Among all the cultivars, C. flexuosus cultivars demonstrated a higher dissipation rate of CP along with more root exudation.

Network regulation meets substrate modification chemistry.

Biochemical networks are at the heart of cellular information processing. These networks contain distinct facets: (i) processing of information from the environment via cascades/pathways along with network regulation and (ii) modification of substrates in different ways, to confer protein functionality, stability and processing. While many studies focus on these factors individually, how they interact and the consequences for cellular systems behaviour are poorly understood. We develop a systems framework for this purpose by examining the interplay of network regulation (canonical feedback and feed-forward circuits) and multisite modification, as an exemplar of substrate modification. Using computational, analytical and semi-analytical approaches, we reveal distinct and unexpected ways in which the substrate modification and network levels combine and the emergent behaviour arising therefrom. This has important consequences for dissecting the behaviour of specific signalling networks, tracing the origins of systems behaviour, inference of networks from data, robustness/evolvability and multi-level engineering of biomolecular networks. Overall, we repeatedly demonstrate how focusing on only one level (say network regulation) can lead to profoundly misleading conclusions about all these aspects, and reveal a number of important consequences for experimental/theoretical/data-driven interrogations of cellular signalling systems.

The spatial resolution limit of phagocytosis

Antibody-opsonized bacteria interact with Fc receptors in macrophages and trigger signaling cascades, which induce phagocytosis. The signaling pathways ultimately lead to actin polymerization that induces the protrusion of the membrane around the bacterium until it is completely engulfed. Although many proteins involved in the phagocytic cup formation have already been identified, it is still unclear how far the initial stimulus created by the bacterium-cell contact propagates in the cell. We hypothesize that this spreading distance is closely related to the spatial resolution limit of phagocytosis, the smallest distance in which two stimuli can be differentiated. Here, we probe this resolution limit by using holographic optical tweezers to attach pairs of immunoglobulin G-coated polystyrene microparticles (as models for opsonized bacteria) to murine macrophages in distances ranging from zero to several micrometers.By using 2-μm-sized particles, we found that the particles can be internalized jointly into one phagosome if they are attached to the cell very close together, but that they are taken up separately if they are attached far from each other. To explain this, we developed a model of the signaling process, which predicts the probabilities for separate uptake for different particle sizes and distances using cellular parameters including the average receptor distance. We tested the model by measuring the separate uptake probabilities for particles with a diameter of 1 to 3 μm and for cells with reduced numbers of Fcγ receptors and found very good agreement. Our model shows that the phagocytic uptake behavior can be explained by assuming an effective phagocytic signaling range of about 500 nm. Interestingly, this value corresponds to the lower size limit of phagocytosis.Our work provides quantitative access to spatial parameters of cellular signaling during phagocytosis and thereby contributes to a more quantitative understanding of cellular information processing.

Transcriptome Profiling Reveals Candidate Genes Related to Stipe Gradient Elongation of Flammulina filiformis.

Stipe gradient elongation is an important and remarkable feature in the development of most mushroom fruiting bodies. However, its molecular mechanism has rarely been described. Here, the decreasing trend of stipe elongation and increasing trend of cell length in a gradient from the top to the base of the stipe were determined in a model basidiomycete mushroom: Flammulina filiformis. According to RNA-seq results, 1409 differentially expressed genes (DEGs) were identified among elongation region (ER), transition region (TR), and stable region (SR) samples, including 26 transcription factors (TFs). Based on Short Time-series Expression Miner (STEM) clustering of DEGs, clusters 1 and 3, with obvious expression trends that were consistent with or in contrast to the elongation rate, were screened. The cluster 1 DEGs were mainly involved in the GO cellular component category and KEGG genetic information processing class; however, the cluster 3 DEGs were mainly involved in metabolic processes. Furthermore, qRT-PCR confirmed that key genes of the long-chain fatty acid synthesis pathway were involved in stipe gradient elongation and regulated by NADPH oxidase-derived ROS signaling molecules. These findings provide an essential basis for understanding the molecular mechanism of stipe gradient elongation.

Activity-Based Proteomic Identification of the S-Thiolation Targets of Ajoene in MDA-MB-231 Breast Cancer Cells.

Garlic is a medicinal plant and spice that has been used for millennia for its health-promoting effects. These medicinal properties are associated with low molecular weight organosulfur compounds, produced following the crushing of garlic cloves. One of these compounds, ajoene, is proposed to act by S-thioallylating cysteine residues on target proteins whose identification in cancer cells holds great promise for understanding mechanistic aspects of ajoene's cancer cell cytotoxicity. To this end, an ajoene analogue (called biotin-ajoene, BA), containing a biotin affinity tag, was designed as an activity-based probe specific for the protein targets of ajoene in MDA-MB-231 breast cancer cells. BA was synthesized via a convergent "click" strategy and found to retain its cytotoxicity against MDA-MB-231 cells compared to ajoene. Widespread biotinylation of proteins was found to occur via disulfide bond formation in a dose-dependent manner, and the biotin-ajoene probe was found to share the same protein targets as its parent compound, ajoene. The biotinylated proteins were affinity-purified from the treated MDA-MB-231 cell lysate using streptavidin-coated magnetic beads followed by an on-bead reduction, alkylation, and digestion to liberate the peptide fragments, which were analyzed by liquid chromatography tandem mass chromatography. A total of 600 protein targets were identified, among which 91% overlapped with proteins with known protein cysteine modification (PCM) sites. The specific sites were enriched for those susceptible to S-glutathionylation (-SSG) (16%), S-sulfhydration (-SSH) (20%), S-sulfenylation (-SOH) (22%), and S-nitrosylation (-SNO) (31%). As target validation, both ajoene and a dansylated ajoene (DP) were found to S-thiolate the pure recombinant forms of glutathione S-transferase pi 1 (GSTP1) and protein disulfide isomerase (PDI), and the ajoene analogue DP was found to be a more potent inhibitor than 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB). Pathway analysis elucidated that ajoene targets functional and signaling pathways that are implicated in cancer cell survival, specifically cellular processes, metabolism, and genetic information processing pathways. The results of this study provide mechanistic insights into the character of the anti-cancer activity of the natural dietary compound ajoene.

Insight into Ultrasound-Induced Modifications of the Proteome and Flavor-Related Proteins of Unsmoked Bacon by Applying Label-Free Quantitation Technology.

The aim of this study was to investigate the modifications of the proteome and flavor-related proteins in unsmoked bacon resulting from ultrasound treatment with the application of label-free quantitation technology together with bioinformatics analysis. Results showed that the expression levels of 137 proteins were markedly affected by ultrasound with most of them being significantly upregulated. The proteins distributed in the cytoplasm and the cytosol, the mitochondrion, and the nucleus were more susceptible to ultrasound treatment. Meanwhile, 20 flavor-related proteins, mostly myofibrillar proteins and metabolic enzymes mainly involved in the metabolic pathways of signaling and cellular processes and environmental information processing, were screened out. In addition, the differential expressions of flavor-related proteins induced by ultrasound were verified by western blotting. This study displayed insightful information from the proteomics perspective for a better understanding of the influential effect of ultrasound treatment on meat flavor.

Synthetic gene networks recapitulate dynamic signal decoding and differential gene expression.

Cells live in constantly changing environments and employ dynamic signaling pathways to transduce information about the signals they encounter. However, the mechanisms by which dynamic signals are decoded into appropriate gene expression patterns remain poorly understood. Here, we devise networked optogenetic pathways that achieve dynamic signal processing functions that recapitulate cellular information processing. Exploiting light-responsive transcriptional regulators with differing response kinetics, we build a falling edge pulse detector and show that this circuit can be employed to demultiplex dynamically encoded signals. We combine this demultiplexer with dCas9-based gene networks to construct pulsatile signal filters and decoders. Applying information theory, we show that dynamic multiplexing significantly increases the information transmission capacity from signal to gene expression state. Finally, we use dynamic multiplexing for precise multidimensional regulation of a heterologous metabolic pathway. Our results elucidate design principles of dynamic information processing and provide original synthetic systems capable of decoding complex signals for biotechnological applications.

Synaptic Integration in CA1 Pyramidal Neurons Is Intact despite Deficits in GABAergic Transmission in the Scn1a Haploinsufficiency Mouse Model of Dravet Syndrome.

Mutations of SCN1A, which encodes the voltage-gated sodium channel Nav1.1, can cause epilepsy disorders such as Dravet syndrome (DS) that are comorbid with wide-ranging neurologic dysfunction. Many studies suggest that Nav1.1 haploinsufficiency causes forebrain GABAergic interneuron hypoexcitability, while pyramidal neuron physiology is mostly unaltered, and that this serves as a primary cell physiology phenotype linking mutation to disease. We hypothesized that deficits in inhibition would alter synaptic integration during activation of the hippocampal microcircuit, thus disrupting cellular information processing and leading to seizures and cognitive deficits. We tested this hypothesis using ex vivo whole-cell recordings from CA1 pyramidal neurons in a heterozygous Scn1a knock-out mouse model and wild-type (WT) littermates, measuring responses to single and patterned synaptic stimulation and spontaneous synaptic activity. Overall, our experiments reveal a surprising normalcy of excitatory and inhibitory synaptic temporal integration in the hippocampus of Scn1a haploinsufficient mice. While miniature IPSCs and feedforward inhibition and were decreased, we did not identify a pattern or frequency of input that caused a failure of synaptic inhibition. We further show that reduced GABA release probability and subsequent reduced short-term depression may act to overcome deficits in inhibition normalizing input/output functions in the Scn1a haploinsufficient hippocampus. These experiments show that CA1 pyramidal neuron synaptic processing is surprisingly robust, even during decreased interneuron function, and more complex circuit activity is likely required to reveal altered function in the hippocampal microcircuit.

Analysis of Phyllosphere Microorganisms and Potential Pathogens of Tobacco Leaves.

In the tobacco phyllosphere, some of the microbes may have detrimental effects on plant health, while many may be neutral or even beneficial. Some cannot be cultivated, so culture-independent methods are needed to explore microbial diversity. In this study, both metagenetic analysis and traditional culture-dependent methods were used on asymptomatic healthy leaves and symptomatic diseased leaves of tobacco plants. In the culture-independent analysis, asymptomatic leaves had higher microbial diversity and richness than symptomatic leaves. Both asymptomatic and symptomatic leaves contained several potentially pathogenic bacterial and fungal genera. The putative bacterial pathogens, such as species of Pseudomonas, Pantoea, or Ralstonia, and putative fungal pathogens, such as species of Phoma, Cladosporium, Alternaria, Fusarium, Corynespora, and Epicoccum, had a higher relative abundance in symptomatic leaves than asymptomatic leaves. FUNGuild analysis indicated that the foliar fungal community also included endophytes, saprotrophs, epiphytes, parasites, and endosymbionts. PICRUSt analysis showed that the dominant functions of the bacterial community in a symptomatic leaf were cellular processes and environmental information processing. In the other five foliar samples, the dominant functions of the bacterial community were genetic information processing, metabolism, and organismal systems. In the traditional culture-dependent method, 47 fungal strains were isolated from 60 symptomatic tobacco leaf fragments bearing leaf spots. Among them, 21 strains of Colletotrichum (29%), Xylariaceae (14%), Corynespora (14%), Pestalotiopsis (10%), Alternaria (10%), Epicoccum (10%), Byssosphaeria (5%), Phoma (5%), and Diaporthe (5%) all fulfilled Koch’s postulates and were found to cause disease on detached tobacco leaves in artificial inoculation tests. Symptoms on detached leaves caused by three strains of Corynespora cassiicola in artificial inoculation tests were similar to the original disease symptoms in the tobacco field. This study showed that the combined application of culture-dependent and independent methods could give comprehensive insights into microbial composition that each method alone did not reveal.

Characterization of hydrocarbon degrading microorganisms from Glycine max and Zea mays phytoremediated crude oil contaminated soil.

Microbe-plant partnership in phytoremediation involves a synergistic interaction that leads to degradation of contaminants. The identification and characterization of these microorganisms is fundamental in environmental management. This study is aimed at investigating the influence of Glycine max and Zea mays on microbial make-up and differentiation of soil bacterial and fungal isolates in crude oil contaminated soil. We employed conventional technique of microbial isolation and gene sequencing to evaluate the microbial composition in crude oil contaminated soil. The microorganisms were isolated from crude oil contaminated soil (0%, 4%, 8%) and were identified using 16S rRNA gene (for bacteria) and Internal Transcribed Spacer (ITS) gene (for fungi). We observed a change in the microbial cell density with respect to treatment conditions implying a shift in microbial dynamics to total hydrocarbon utilizing bacteria as the dominant microbes. The sequence data revealed five bacteria strain; Klebsiella aerogenes strain 77, Klebsiella aerogenes strain UISO178, Salmonella enterica strain ABUH7, Klebsiella aerogenes strain M242 and Enterobacter sp. NCCP-607 and three fungi strains; Galactomyces geotrichum strain CBS, Aspergillus niger strain YMCHA73 and Trichoderma virens isolate A701. Annotation analysis using FGENESB and gene scan revealed proteins involved in various metabolic processes and hydrocarbon utilization. GHOSTKOLA output revealed several genetic elements and pathways such as DnaA, PYG, mrcA, environmental, cellular and genetic information processing and degradation enhancers. Our findings show that G. max and Z. mays in association with bacteria can enhance ecosystem restoration of crude oil contaminated soil.

Community-acquired methicillin-resistant Staphylococcus aureus provoked cytokine storm causing severe infection on BALB/c mice

Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important pathogen of hospital-acquired (HA) or community-acquired (CA) infections. However, it is unclear of the cytokines responsible for pathological hyper-inflammation in sepsis related cytokine storm for MRSA infection. In this study, we selected typical HA-MRSA strain (YNSA163: ST239-t030-SCCmecⅢ) and two CA-MRSA isolates (YNSA7: ST59-t439-SCCmecⅣa and YNSA53: ST59-t437-SCCmecⅤb) from our previous research, infected on BALB/c mice, and analyzed the cytokine storm patterns during infection process. The animal experiments revealed the most serious lethal effect on BALB/c mice caused by YNSA7 strain infection, followed by YNSA53, and no BALB/c mice died for YNSA163 infection. Histopathological analyses revealed that lung was the most seriously damaged organs, followed by spleen and kidney, especially for CA-MRSA infection. The severe inflammatory reactions, tissue destruction, and massive exudation of inflammatory mediators and cells could be identified in CA-MRSA strains infected mice. Interleukin-6 (IL-6) and IL-10 were both highly expressed in spleen and lung of YNSA7 and YNSA53 dead cases compared with YNSA53 survived and YNSA163 cases, which demonstrated cytokine storm pattern for CA-MRSA strains infection. The results of IL-6 intervention experiment verified that the enhanced IL-6 secretion was responsible for the host lethality of YNSA7 infection. RNA-sequencing results among three MRSA isolates indicated most of the differentially expressed genes referred to cellular process, metabolism and genetic information processing of bacteria. Specifically, clpP, chp chemotaxis inhibit, fnbB, pathogencity island protein and virulence associated protein E were highly expressed in YNSA7 strain. In general, CA-MRSA strains provoked cytokine storm on BALB/c mice led to severe infection and lethality, the up-regulated of some virulence genes might play important role in pathogenesis.

Gut microbiome architecture of wild greater one-horned rhinoceros: a vulnerable species from Kaziranga National Park, India

Rhinoceros unicornis, also known as the greater one-horned rhinoceros (GoHR), is a vulnerable wildlife species found in the Indian subcontinent with an estimated global population of 3582, of which an estimated 2995 resides in India. The Kaziranga National Park of Assam is the home to ~80.56% of the GoH population in India. Recent advances in genetics and microbial studies underscored the importance of gut microbial symbiosis as a crucial factor for host metabolic health and environmental interaction, particularly for higher mammals. Alteration of the normal microbiome can also be an indicator of chronic disease and infection. Freshly voided dung samples from nine dung heaps of free ranging or wild GoH rhinoceros were collected from Kaziranga National Park for mapping the gut microbial architecture through 16S-metagenomic approach. In our sample, the GoH gut harbours 168.8±12.55 (SE) bacteria-specific OTUs belonging to 21 phyla of which the gram-negative Proteobacteria is the most abundant phyla. Other abundant phylas found in the GoH gut are Firmicutes and Bacteroidetes. Although the GoH rhinoceros gut can utilize fibrous plant by microbial fermentation, the aerobic, nonfermenting Acinetobacter (20.7%), Stenotrophomonas (17.8%) and Brevundimonas (9.1%) constitute about 50% of all identified genus. Functional prediction of the GoH microbiome reveals that>50% of the bacteria present are involved in metabolism followed by cellular processes and information processing. A significant proportion (>1%) are associated with different diseases. In summary, our study characterized bacterial communities of nine wild GoH to identify some unique features and its implication in disease and survival of GoH.