GTex: Alles vernetzt Groß, Michael
Chemie in unserer Zeit,
12/2017, Letnik:
51, Številka:
6
Journal Article
Recenzirano
Das Netzwerk eines lebenden Organismus ist unglaublich kompliziert, wie wir in dieser Serie an ausgewählten Beispielen gesehen haben. Das menschliche Genom ist nur einer der Ansatzpunkte zur ...Erschließung der Zusammenhänge. Um medizinisch relevante Einblicke in die Ursachen von Krankheiten zu gewinnen, müssen wir verstehen lernen, wie das im ganzen Körper nahezu einheitliche Genom in verschiedenen Zellen und Geweben zu völlig verschiedenen Ausprägungen (Phänotypen) führt, und wie diese Verbindungen durch Mutationen beeinflusst werden. Diese gigantische Aufgabe geht das Gtex‐Projekt (Genotype Tissue Expression) an, das soeben eine umfassende Auswertung seiner Ergebnisse publiziert hat.
Three carbapenem-resistant
Escherichia coli
were recovered from rectal swabs of different patients in a tertiary hospital and were found carrying
bla
NDM-4,
an uncommon
bla
NDM
variant. Genome ...sequences of the isolates were obtained using Illumina technology and the long-read MinION sequencer. The isolates belonged to ST405 and phylogenetic group D, a globally distributed lineage associated with antimicrobial resistance. In addition to
bla
NDM-4
, the three isolates carried 14 known resistance genes including the extended-spectrum β-lactamase gene
bla
CTX-M-15
. There were only 1 or 2 SNPs between the isolates, suggesting a common origin and cryptic transmission in hospital.
bla
NDM-4
was located on a 46.5-kb IncFIA self-transmissible plasmid, which may facilitate further dissemination of
bla
NDM-4
. Two copies of IS
26
bracketed a 14.6-kb region containing
bla
NDM-4
and have the potential to form a composite transposon for mediating the mobilization of
bla
NDM-4
.
Throughout the animal kingdom, mitochondria are the only organelles that retain their own genome and the transcription and translation machineries that are all essential for energy harvesting. ...Mitochondria have developed a complex communication network, allowing them to stay in tune with cellular needs and nuclear transcriptional programs and to alleviate mitochondrial dysfunction. Here, we review recent findings on the wide array of mechanisms that contribute to these mitocellular communication networks, spanning from well-studied messenger molecules to mitonuclear genetic interactions. Based on these observations and developments, we advocate a broad and inclusive view on mitocellular interactions, which can have profound impacts on physiological, pathological, and evolutionary processes.
The recent successes of the Materials Genome Initiative have opened up new opportunities for data-centric informatics approaches in several subfields of materials research, including in polymer ...science and engineering. Polymers, being inexpensive and possessing a broad range of tunable properties, are widespread in many technological applications. The vast chemical and morphological complexity of polymers though gives rise to challenges in the rational discovery of new materials for specific applications. The nascent field of polymer informatics seeks to provide tools and pathways for accelerated property prediction (and materials design) via surrogate machine learning models built on reliable past data. We have carefully accumulated a data set of organic polymers whose properties were obtained either computationally (bandgap, dielectric constant, refractive index, and atomization energy) or experimentally (glass transition temperature, solubility parameter, and density). A fingerprinting scheme that captures atomistic to morphological structural features was developed to numerically represent the polymers. Machine learning models were then trained by mapping the fingerprints (or features) to properties. Once developed, these models can rapidly predict properties of new polymers (within the same chemical class as the parent data set) and can also provide uncertainties underlying the predictions. Since different properties depend on different length-scale features, the prediction models were built on an optimized set of features for each individual property. Furthermore, these models are incorporated in a user-friendly online platform named Polymer Genome (www.polymergenome.org). Systematic and progressive expansion of both chemical and property spaces are planned to extend the applicability of Polymer Genome to a wide range of technological domains.
Monascus purpureus
, a pigment-producing ascomycetous fungus, has been traditionally used for red rice preparation using solid-state fermentation. The objective of this study was to develop an ...improved pigment-producing strain of
M. purpureus
MTCC 1090 through genome shuffling followed by detailed analytical estimations of pigments and other bioactive compounds produced by the fusant. Protoplast formation was optimum with 12 h-old mycelia incubated at 30 °C with cellulase, lyticase, and chitinase (40:1:1) for 5 h. Four UV-induced mutants that produced 13.1–39.5% higher amount of yellow, orange, and red pigments in fermented low-grade (cheap) broken rice were used as parents for genome shuffling. After the first round of fusion, four fusants with 35.9–60.52% higher pigment production capabilities were fused again, and finally the fusant F2-19 with distinct culture characteristic was selected under multi-selection pressure. It consistently produced 67%, 70%, and 76% higher content of yellow, orange, and red pigments respectively as compared to the wild-type. High-performance liquid chromatography (HPLC) analysis also reveals clear variation in pigment productions between wild-type and the fusant. Furthermore, HPLC analysis of F2-19 fermented rice extract confirms the production of 186 ± 8.71 and 3810 ± 29.81 mg/kg mevinolin and gamma-aminobutyric acid respectively. Citrinin was not detected. F2-19 fermented rice also has high antioxidant activity (7.92 ± 0.32 mg/g trolox equivalent), with good amount of phenolics (18.0 ± 0.95 mg/g gallic acid equivalent) and flavonoids (2.7 ± 0.26 mg/g quercetin equivalent). Thus, genome shuffling was successfully implemented on
M. purpureus
for the first time to develop a citrinin-free, better-performing fusant that holds future biotechnological potential.
Key points
• Genome shuffling was performed by recursive protoplast fusion in Monascus purpureus.
• The selected fusant, F2-19, was used in solid-state fermentation using low-grade rice.
• It produced 67–76% higher content of yellow, orange, and red pigments than the wild-type.
• HPLC detected 186 mg/kg mevinolin and 3810 mg/kg γ-aminobutyric acid, but no citrinin.
• F2-19 shows high antioxidant activity with good amount of phenolics and flavonoids.
Graphical abstract
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Lithium–sulfur (Li–S) batteries are considered as promising candidates for next-generation energy storage devices due to their ultrahigh theoretical gravimetric energy density, ...cost-effectiveness, and environmental friendliness. However, the application of Li–S batteries remains challenging, mainly due to a lack of understanding of the complex chemical reactions and associated equilibria occurring in a working Li–S system. In this review, the typical applications of computational chemistry in Li–S battery studies, correlating to characterization techniques, such as X-ray diffraction, infra-red & Raman spectra, X-ray absorption spectroscopy, binding energy, and nuclear magnetic resonance, are reviewed. In particular, high-accuracy calculations and large-scale models, materials genome, and machine-learning approaches are expected to further advance computational design for the development of Li–S batteries and related fields.
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The Materials Genome Initiative (MGI) has heralded a sea change in the philosophy of materials design. In an increasing number of applications, the successful deployment of novel ...materials has benefited from the use of computational methodologies, data descriptors, and machine learning. Polymers have long suffered from a lack of data on electronic, mechanical, and dielectric properties across large chemical spaces, causing a stagnation in the set of suitable candidates for various applications. Extensive efforts over the last few years have seen the fruitful application of MGI principles toward the accelerated discovery of attractive polymer dielectrics for capacitive energy storage. Here, we review these efforts, highlighting the importance of computational data generation and screening, targeted synthesis and characterization, polymer fingerprinting and machine-learning prediction models, and the creation of an online knowledgebase to guide ongoing and future polymer discovery and design. We lay special emphasis on the fingerprinting of polymers in terms of their genome or constituent atomic and molecular fragments, an idea that pays homage to the pioneers of the human genome project who identified the basic building blocks of the human DNA. By scoping the polymer genome, we present an essential roadmap for the design of polymer dielectrics, and provide future perspectives and directions for expansions to other polymer subclasses and properties.
Effective and cell-type-specific delivery of CRISPR/Cas9 gene editing elements remains a challenging open problem. Here we report the development of biomimetic cancer cell coated zeolitic imidazolate ...frameworks (ZIFs) for targeted and cell-specific delivery of this genome editing machinery. Coating ZIF-8 that is encapsulating CRISPR/Cas9 (CC-ZIF) with a cancer cell membrane resulted in the uniformly covered C3-ZIF(cell membrane type). Incubation of C3-ZIFMCF with MCF-7, HeLa, HDFn, and aTC cell lines showed the highest uptake by MCF-7 cells and negligible uptake by the healthy cells (i.e., HDFn and aTC). As to genome editing, a 3-fold repression in the EGFP expression was observed when MCF-7 were transfected with C3-ZIFMCF compared to 1-fold repression in the EGFP expression when MCF-7 were transfected with C3-ZIFHELA. In vivo testing confirmed the selectivity of C3-ZIFMCF to accumulate in MCF-7 tumor cells. This supports the ability of this biomimetic approach to match the needs of cell-specific targeting, which is unquestionably the most critical step in the future translation of genome editing technologies.
Beyond its remarkable genome editing ability, the CRISPR/Cas9 effector has also been utilized in biosensing applications. The recent discovery of the collateral RNA cleavage activity of the Cas13a ...effector has sparked even greater interest in developing novel biosensing technologies for nucleic acid detection and promised significant advances in CRISPR diagnostics. Now, along with the discovery of Cas12 collateral cleavage activities on single-stranded DNA (ssDNA), several CRISPR/Cas systems have been established for detecting various targets, including bacteria, viruses, cancer mutations, and others. Based on key Cas effectors, we provide a detailed classification of CRISPR/Cas biosensing systems and propose their future utility. As the field continues to mature, CRISPR/Cas systems have the potential to become promising candidates for next-generation diagnostic biosensing platforms.
CRISPR/Cas biosensing systems transfer the sequence information of target nucleic acids to detectable signals such as fluorescence and colorimetric values.
CRISPR/Cas biosensing systems are versatile platforms for nucleic acid detection that can be used for pathogen detection and genotyping, cancer mutation detection, and single nucleotide polymorphism (SNP) identification.
The biosensing methods employing these Cas effectors rely on the collateral cleavage activities of Cas13 and Cas12.
CRISPR/Cas biosensing allows highly sensitive, specific, rapid, cost-efficient, and multiplex detection of target nucleic acids, and support point-of-care use without the need for technical expertise and complicated equipment.
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