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A pure culture of the complete nitrifier Nitrospira inopinata shows a high affinity for ammonia, low maximum rate of ammonia oxidation, high growth yield compared to canonical nitrifiers and genomic potential for alternative metabolisms, probably reflecting an important role in nitrification in oligotrophic environments. Nutrient-starved nitrification Nitrospira inopinata was the first bacterium identified that is capable of catalysing complete ammonia oxidization (referred to as comammox). Holger Daims and colleagues now report a pure culture of this organism, which enabled a characterization of its physiology. The authors find that N. inopinata has a high affinity for ammonia, a low maximum rate of ammonia oxidation, a high growth yield compared to canonical nitrifiers, and the genomic potential for alternative metabolisms. The team compare the nitrification kinetics of N. inopinata to that of four ammonia-oxidizing archaea. The results suggest that N. inopinata is likely to have an important role in nitrification, especially in oligotrophic environments. Nitrification, the oxidation of ammonia (NH 3 ) via nitrite (NO 2 − ) to nitrate (NO 3 − ), is a key process of the biogeochemical nitrogen cycle. For decades, ammonia and nitrite oxidation were thought to be separately catalysed by ammonia-oxidizing bacteria (AOB) and archaea (AOA), and by nitrite-oxidizing bacteria (NOB). The recent discovery of complete ammonia oxidizers (comammox) in the NOB genus Nitrospira 1 , 2 , which alone convert ammonia to nitrate, raised questions about the ecological niches in which comammox Nitrospira successfully compete with canonical nitrifiers. Here we isolate a pure culture of a comammox bacterium, Nitrospira inopinata , and show that it is adapted to slow growth in oligotrophic and dynamic habitats on the basis of a high affinity for ammonia, low maximum rate of ammonia oxidation, high growth yield compared to canonical nitrifiers, and genomic potential for alternative metabolisms. The nitrification kinetics of four AOA from soil and hot springs were determined for comparison. Their surprisingly poor substrate affinities and lower growth yields reveal that, in contrast to earlier assumptions, AOA are not necessarily the most competitive ammonia oxidizers present in strongly oligotrophic environments and that N. inopinata has the highest substrate affinity of all analysed ammonia oxidizer isolates except the marine AOA Nitrosopumilus maritimus SCM1 (ref. 3 ). These results suggest a role for comammox organisms in nitrification under oligotrophic and dynamic conditions.

Nitrification, the oxidation of ammonia via nitrite to nitrate, has always been considered to be a two-step process catalysed by chemolithoautotrophic microorganisms oxidizing either ammonia or nitrite. No known nitrifier carries out both steps, although complete nitrification should be energetically advantageous. This functional separation has puzzled microbiologists for a century. Here we report on the discovery and cultivation of a completely nitrifying bacterium from the genus Nitrospira , a globally distributed group of nitrite oxidizers. The genome of this chemolithoautotrophic organism encodes the pathways both for ammonia and nitrite oxidation, which are concomitantly activated during growth by ammonia oxidation to nitrate. Genes affiliated with the phylogenetically distinct ammonia monooxygenase and hydroxylamine dehydrogenase genes of Nitrospira are present in many environments and were retrieved on Nitrospira -contigs in new metagenomes from engineered systems. These findings fundamentally change our picture of nitrification and point to completely nitrifying Nitrospira as key components of nitrogen-cycling microbial communities. Until now, the oxidation steps necessary for complete nitrification have always been observed to occur in two separate microorganisms in a cross-feeding interaction; here, together with the study by van Kessel et al ., Daims et al . report the enrichment and characterization of Nitrospira species that encode all of the enzymes necessary to catalyse complete nitrification, a phenotype referred to as “comammox” (for complete ammonia oxidation). Time to rethink nitrification Two groups this week report the enrichment and characterization of Nitrospira species that encode all of the enzymes necessary to catalyse complete nitrification, a phenotype referred to as 'comammox' (for complete ammonia oxidation). Until now, this two-step reaction was thought to involve two organisms in a cross-feeding interaction. Phylogenetic analyses suggest that comammox Nitrospira are present in a number of diverse environments, so these findings have the potential to fundamentally change our view of the nitrogen cycle and open a new frontier in nitrification research.

The discovery of ammonia-oxidizing archaea (AOA) of the phylum Thaumarchaeota and the high abundance of archaeal ammonia monooxygenase subunit A encoding gene sequences in many environments have extended our perception of nitrifying microbial communities. Moreover, AOA are the only aerobic ammonia oxidizers known to be active in geothermal environments. Molecular data indicate that in many globally distributed terrestrial high-temperature habits a thaumarchaeotal lineage within the Nitrosopumilus cluster (also called \"marine\" group I.1a) thrives, but these microbes have neither been isolated from these systems nor functionally characterized in situ yet. In this study, we report on the enrichment and genomic characterization of a representative of this lineage from a thermal spring in Kamchatka. This thaumarchaeote, provisionally classified as \"Candidatus Nitrosotenuis uzonensis\", is a moderately thermophilic, non-halophilic, chemolithoautotrophic ammonia oxidizer. The nearly complete genome sequence (assembled into a single scaffold) of this AOA confirmed the presence of the typical thaumarchaeotal pathways for ammonia oxidation and carbon fixation, and indicated its ability to produce coenzyme F420 and to chemotactically react to its environment. Interestingly, like members of the genus Nitrosoarchaeum, \"Candidatus N. uzonensis\" also possesses a putative artubulin-encoding gene. Genome comparisons to related AOA with available genome sequences confirmed that the newly cultured AOA has an average nucleotide identity far below the species threshold and revealed a substantial degree of genomic plasticity with unique genomic regions in \"Ca. N. uzonensis\", which potentially include genetic determinants of ecological niche differentiation.

The recent discovery of ammonia-oxidizing archaea (AOA) dramatically changed our perception of the diversity and evolutionary history of microbes involved in nitrification. In this study, a moderately thermophilic (46°C) ammonia-oxidizing enrichment culture, which had been seeded with biomass from a hot spring, was screened for ammonia oxidizers. Although gene sequences for crenarchaeotal 16S rRNA and two subunits of the ammonia monooxygenase (amoA and amoB) were detected via PCR, no hints for known ammonia-oxidizing bacteria were obtained. Comparative sequence analyses of these gene fragments demonstrated the presence of a single operational taxonomic unit and thus enabled the assignment of the amoA and amoB sequences to the respective 16S rRNA phylotype, which belongs to the widely distributed group I.1b (soil group) of the CRENARCHAEOTA: Catalyzed reporter deposition (CARD)-FISH combined with microautoradiography (MAR) demonstrated metabolic activity of this archaeon in the presence of ammonium. This finding was corroborated by the detection of amoA gene transcripts in the enrichment. CARD-FISH/MAR showed that the moderately thermophilic AOA is highly active at 0.14 and 0.79 mM ammonium and is partially inhibited by a concentration of 3.08 mM. The enriched AOA, which is provisionally classified as \"Candidatus Nitrososphaera gargensis,\" is the first described thermophilic ammonia oxidizer and the first member of the crenarchaeotal group I.1b for which ammonium oxidation has been verified on a cellular level. Its preference for thermophilic conditions reinvigorates the debate on the thermophilic ancestry of AOA.

We propose a memristive interface consisting of two FitzHugh–Nagumo electronic neurons connected via a metal–oxide (Au/Zr/ZrO2(Y)/TiN/Ti) memristive synaptic device. We create a hardware–software complex based on a commercial data acquisition system, which records a signal generated by a presynaptic electronic neuron and transmits it to a postsynaptic neuron through the memristive device. We demonstrate, numerically and experimentally, complex dynamics, including chaos and different types of neural synchronization. The main advantages of our system over similar devices are its simplicity and real-time performance. A change in the amplitude of the presynaptic neurogenerator leads to the potentiation of the memristive device due to the self-tuning of its parameters. This provides an adaptive modulation of the postsynaptic neuron output. The developed memristive interface, due to its stochastic nature, simulates a real synaptic connection, which is very promising for neuroprosthetic applications.

The effects of chronic alcohol consumption on the bowel flora and the potential therapeutic role of probiotics in alcohol-induced liver injury have not previously been evaluated. In this study, 66 adult Russian males admitted to a psychiatric hospital with a diagnosis of alcoholic psychosis were enrolled in a prospective, randomized, clinical trial to study the effects of alcohol and probiotics on the bowel flora and alcohol-induced liver injury. Patients were randomized to receive 5 days of Bifidobacterium bifidum and Lactobacillus plantarum 8PA3 versus standard therapy alone (abstinence plus vitamins). Stool cultures and liver enzymes were performed at baseline and again after therapy. Results were compared between groups and with 24 healthy, matched controls who did not consume alcohol. Compared to healthy controls, alcoholic patients had significantly reduced numbers of bifidobacteria (6.3 vs. 7.5 log colony-forming unit [CFU]/g), lactobacilli (3.15 vs. 4.59 log CFU/g), and enterococci (4.43 vs. 5.5 log CFU/g). The mean baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT) activities were significantly elevated in the alcoholic group compared to the healthy control group (AST: 104.1 vs. 29.15 U/L; ALT: 50.49 vs. 22.96 U/L; GGT 161.5 vs. 51.88 U/L), indicating that these patients did have mild alcohol-induced liver injury. After 5 days of probiotic therapy, alcoholic patients had significantly increased numbers of both bifidobacteria (7.9 vs. 6.81 log CFU/g) and lactobacilli (4.2 vs. 3.2 log CFU/g) compared to the standard therapy arm. Despite similar values at study initiation, patients treated with probiotics had significantly lower AST and ALT activity at the end of treatment than those treated with standard therapy alone (AST: 54.67 vs. 76.43 U/L; ALT 36.69 vs. 51.26 U/L). In a subgroup of 26 subjects with well-characterized mild alcoholic hepatitis (defined as AST and ALT greater than 30 U/L with AST-to-ALT ratio greater than one), probiotic therapy was associated with a significant end of treatment reduction in ALT, AST, GGT, lactate dehydrogenase, and total bilirubin. In this subgroup, there was a significant end of treatment mean ALT reduction in the probiotic arm versus the standard therapy arm. In conclusion, patients with alcohol-induced liver injury have altered bowel flora compared to healthy controls. Short-term oral supplementation with B. bifidum and L. plantarum 8PA3 was associated with restoration of the bowel flora and greater improvement in alcohol-induced liver injury than standard therapy alone.

We present a novel closed-loop system designed to integrate biological and artificial neurons of the oscillatory type into a unified circuit. The system comprises an electronic circuit based on the FitzHugh-Nagumo model, which provides stimulation to living neurons in acute hippocampal mouse brain slices. The local field potentials generated by the living neurons trigger a transition in the FitzHugh–Nagumo circuit from an excitable state to an oscillatory mode, and in turn, the spikes produced by the electronic circuit synchronize with the living-neuron spikes. The key advantage of this hybrid electrobiological autogenerator lies in its capability to control biological neuron signals, which holds significant promise for diverse neuromorphic applications.

An underlying mechanism for multi drug resistance (MDR) is up-regulation of the transmembrane ATP-binding cassette (ABC) transporter proteins. ABC transporters also determine the general fate and effect of pharmaceutical agents in the body. The three major types of ABC transporters are MDR1 (P-gp, P-glycoprotein, ABCB1), MRP1/2 (ABCC1/2) and BCRP/MXR (ABCG2) proteins. Flow cytometry (FCM) allows determination of the functional expression levels of ABC transporters in live cells, but most dyes used as indicators (rhodamine 123, DiOC(2)(3), calcein-AM) have limited applicability as they do not detect all three major types of ABC transporters. Dyes with broad coverage (such as doxorubicin, daunorubicin and mitoxantrone) lack sensitivity due to overall dimness and thus may yield a significant percentage of false negative results. We describe two novel fluorescent probes that are substrates for all three common types of ABC transporters and can serve as indicators of MDR in flow cytometry assays using live cells. The probes exhibit fast internalization, favorable uptake/efflux kinetics and high sensitivity of MDR detection, as established by multidrug resistance activity factor (MAF) values and Kolmogorov-Smirnov statistical analysis. Used in combination with general or specific inhibitors of ABC transporters, both dyes readily identify functional efflux and are capable of detecting small levels of efflux as well as defining the type of multidrug resistance. The assay can be applied to the screening of putative modulators of ABC transporters, facilitating rapid, reproducible, specific and relatively simple functional detection of ABC transporter activity, and ready implementation on widely available instruments.

A new sorption material (GS) was obtained by the modification of heulandite zeolite (G) with N,N′-bis-(3-triethoxysilylpropyl)thiocarbamide (S). The composition, structure, and surface morphology of the GS material were confirmed using elemental analysis, IR-, NMR-spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), elemental mapping, and nitrogen adsorption/desorption (BET). The potential of GS as a sorbent for the removal of Cu(II) and Ni(II) ions from concentrated solutions was demonstrated. The nature of the adsorption of Cu(II) and Ni(II) ions was investigated using the Langmuir, Freundlich, and Dubinin–Radushkevich models. The adsorption value of Cu(II) and Ni(II) ions by the GS sorbent was found to be 1.7 and 2.1 times higher than that of heulandite, amounting to 0.128 mmol/g (8.1 mg/g) and 0.214 mmol/g (12.6 mg/g), respectively. The free energy of adsorption E for the adsorption of Cu(II) and Ni(II) ions was determined to be 12.5 and 16.2 kJ/mol, respectively. Calculations of changes in Gibbs energy based on quantum chemical modeling results (ΔG2980 = −38.5 kJ/mol for Ni and ΔG2980 = −56.5 kJ/mol for Cu) confirmed that adsorption of heavy metal ions onto the GS sample occurs through the formation of metal ion coordination complexes with the sorbent’s functional groups (chemosorption). The proposed method of obtaining new sorption materials based on natural heulandite is straightforward and cost-effective, enabling the production of high-capacity sorption products.

We propose an optoelectronic system for stimulation of living neurons. The system consists of an electronic circuit based on the FitzHugh-Nagumo model, an optical fiber, and a photoelectrical converter. We used this system for electrical stimulation of hippocampal living neurons in acute hippocampal brain slices (350-μm thick) obtained from a 20-28 days old C57BL/6 mouse or a Wistar rat. The main advantage of our system over other similar stimulators is that it contains an optical fiber for signal transmission instead of metallic wires. The fiber is placed between the electronic circuit and stimulated neurons and provides galvanic isolation from external electrical and magnetic fields. The use of the optical fiber allows avoiding electromagnetic noise and current flows which could affect metallic wires. Furthermore, it gives us the possibility to simulate \"synaptic plasticity\" by adaptive signal transfer through optical fiber. The proposed optoelectronic system (hybrid neural circuit) provides a very high efficiency in stimulating hippocampus neurons and can be used for restoring brain activity in particular regions or replacing brain parts (neuroprosthetics) damaged due to a trauma or neurodegenerative diseases.