Survival strategies of aerobic methanotrophs under hypoxia in methanogenic lake sediments.

Background: Microbial methane oxidation, methanotrophy, plays a crucial role in mitigating the release of the potent greenhouse gas methane from aquatic systems. While aerobic methanotrophy is a well-established process in oxygen-rich environments, emerging evidence suggests their activity in hypoxic conditions. However, the adaptability of these methanotrophs to such environments has remained poorly understood.

Exposure-response relationship between work-related hand-arm vibration exposure and musculoskeletal disorders of the upper extremities: the German hand-arm vibration study.

To quantify the exposure-response relationship between hand-arm vibration exposure and the risk of musculoskeletal disorders of the upper extremities (UMSDs), a case-control study was carried out among workers in the construction, mining, metal and woodworking industries. . In total, 209 male cases and 614 controls were recruited.

Aerobic methanotrophy increases the net iron reduction in methanogenic lake sediments.

In methane (CH) generating sediments, methane oxidation coupled with iron reduction was suggested to be catalyzed by archaea and bacterial methanotrophs of the order Methylococcales. However, the co-existence of these aerobic and anaerobic microbes, the link between the processes, and the oxygen requirement for the bacterial methanotrophs have remained unclear. Here, we show how stimulation of aerobic methane oxidation at an energetically low experimental environment influences net iron reduction, accompanied by distinct microbial community changes and lipid biomarker patterns.

Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties.

The α6β4 nicotinic acetylcholine receptor (nAChR) is enriched in dorsal root ganglia neurons and is an attractive non-opioid therapeutic target for pain. However, difficulty expressing human α6β4 receptors in recombinant systems has precluded drug discovery. Here, genome-wide screening identified accessory proteins that enable reconstitution of human α6β4 nAChRs.

Selective inhibition of peripheral cathepsin S reverses tactile allodynia following peripheral nerve injury in mouse.

Cathepsin S (CatS) is a cysteine protease found in lysosomes of hematopoietic and microglial cells and in secreted form in the extracellular space. While CatS has been shown to contribute significantly to neuropathic pain, the precise mechanisms remain unclear. In this report, we describe JNJ-39641160, a novel non-covalent, potent, selective and orally-available CatS inhibitor that is peripherally restricted (non-CNS penetrant) and may represent an innovative class of immunosuppressive and analgesic compounds and tools useful toward investigating peripheral mechanisms of CatS in neuropathic pain.

Aquatic and terrestrial cyanobacteria produce methane.

Evidence is accumulating to challenge the paradigm that biogenic methanogenesis, considered a strictly anaerobic process, is exclusive to archaea. We demonstrate that cyanobacteria living in marine, freshwater, and terrestrial environments produce methane at substantial rates under light, dark, oxic, and anoxic conditions, linking methane production with light-driven primary productivity in a globally relevant and ancient group of photoautotrophs. Methane production, attributed to cyanobacteria using stable isotope labeling techniques, was enhanced during oxygenic photosynthesis.

Iron-Coupled Anaerobic Oxidation of Methane Performed by a Mixed Bacterial-Archaeal Community Based on Poorly Reactive Minerals.

Anaerobic oxidation of methane (AOM) was shown to reduce methane emissions by over 50% in freshwater systems, its main natural contributor to the atmosphere. In these environments iron oxides can become main agents for AOM, but the underlying mechanism for this process has remained enigmatic. By conducting anoxic slurry incubations with lake sediments amended with C-labeled methane and naturally abundant iron oxides the process was evidenced by significant C-enrichment of the dissolved inorganic carbon pool and most pronounced when poorly reactive iron minerals such as magnetite and hematite were applied.

Co-existence of Methanogenesis and Sulfate Reduction with Common Substrates in Sulfate-Rich Estuarine Sediments.

The competition between sulfate reducing bacteria and methanogens over common substrates has been proposed as a critical control for methane production. In this study, we examined the co-existence of methanogenesis and sulfate reduction with shared substrates over a large range of sulfate concentrations and rates of sulfate reduction in estuarine systems, where these processes are the key terminal sink for organic carbon. Incubation experiments were carried out with sediment samples from the sulfate-methane transition zone of the Yarqon (Israel) estuary with different substrates and inhibitors along a sulfate concentrations gradient from 1 to 10 mM.

Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor.

Pain places a devastating burden on patients and society and current pain therapeutics exhibit limitations in efficacy, unwanted side effects and the potential for drug abuse and diversion. Although genetic evidence has clearly demonstrated that the voltage-gated sodium channel, Nav1.7, is critical to pain sensation in mammals, pharmacological inhibitors of Nav1.

The discovery and preclinical characterization of 6-chloro-N-(2-(4,4-difluoropiperidin-1-yl)-2-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)quinoline-5-carboxamide based P2X7 antagonists.

The synthesis, SAR and preclinical characterization of a series of 6-chloro-N-(2-(4,4-difluoropiperidin-1-yl)-2-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)quinoline-5-carboxamide based P2X7 antagonists is described herein. The lead compounds are potent inhibitors in Ca(2+) flux and whole blood IL-1β P2X7 release assays at both human and mouse isoforms. Compound 1e showed a robust reduction of IL-1β release in a mouse ex vivo model with a 50mg/kg oral dose.

Redox stability regulates community structure of active microbes at the sediment-water interface.

Changes in redox conditions occur in a wide range of microbial habitats, in particular at the sediment-water interface (SWI) of aquatic systems. A mesocosm study using intact sediment cores from Lake Stechlin (Germany) was performed to investigate the impact of redox changes on microbial communities at the SWI. The SWI was exposed to permanent oxic (OX) or anoxic (ANOX) or to variable (VR) redox conditions, and for molecular analysis sediment samples were taken at the start and after seven days of the treatment.

Microbial Response to Experimentally Controlled Redox Transitions at the Sediment Water Interface.

The sediment-water interface of freshwater lakes is characterized by sharp chemical gradients, shaped by the interplay between physical, chemical and microbial processes. As dissolved oxygen is depleted in the uppermost sediment, the availability of alternative electron acceptors, e.g.

GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine.

GPR139 is an orphan G-protein-coupled receptor expressed in the central nervous system. To identify its physiologic ligand, we measured GPR139 receptor activity from recombinant cells after treatment with amino acids, orphan ligands, serum, and tissue extracts. GPR139 activity was measured using guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding, calcium mobilization, and extracellular signal-regulated kinases phosphorylation assays.

Annual sulfur cycle in a warm monomictic lake with sub-millimolar sulfate concentrations.

Background: We studied the annual variability of the concentration and isotopic composition of main sulfur species and sulfide oxidation intermediates in the water column of monomictic fresh-water Lake Kinneret. Sulfate concentrations in the lake are <1 mM and similar to concentrations that are proposed to have existed in the Paleoproterozoic ocean. The main goal of this research was to explore biogeochemical constrains of sulfur cycling in the modern low-sulfate fresh-water lake and to identify which processes may be responsible for the isotopic composition of sulfur species in the Precambrian sedimentary rocks.

Aspen shaving versus chip bedding: effects on breeding and behavior.

The choice of laboratory cage bedding material is often based on both practical and husbandry issues, whereas behavioral outcomes rarely appear to be considered. It has been noted that a breeding success difference appears to be associated with the differential use of aspen chip and aspen shaving bedding in our facility; therefore, we sought to analyze breeding records maintained over a 20-month period. In fact, in all four mouse strains analyzed, shaving bedding was associated with a significant increase in average weanlings per litter relative to chip bedding.

Toxicant induced changes on delayed fluorescence decay kinetics of cyanobacteria and green algae: a rapid and sensitive biotest.

Algal tests have developed into routine tools for testing toxicity of pollutants in aquatic environments. Meanwhile, in addition to algal growth rates, an increasing number of fluorescence based methods are used for rapid and sensitive toxicity measures. The present study stresses the suitability of delayed fluorescence (DF) as a promising parameter for biotests.

Microbial methane production in oxygenated water column of an oligotrophic lake.

The prevailing paradigm in aquatic science is that microbial methanogenesis happens primarily in anoxic environments. Here, we used multiple complementary approaches to show that microbial methane production could and did occur in the well-oxygenated water column of an oligotrophic lake (Lake Stechlin, Germany). Oversaturation of methane was repeatedly recorded in the well-oxygenated upper 10 m of the water column, and the methane maxima coincided with oxygen oversaturation at 6 m.

Discovery of a novel series of selective HCN1 blockers.

The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubstituted indane derivatives, which had moderate selectivity and potency at HCN1.

Characterization of 2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(4-trifluoromethyl-phenyl)-amine (JNJ-39729209) as a novel TRPV1 antagonist.

As an integrator of multiple nociceptive and/or inflammatory stimuli, TRPV1 is an attractive therapeutic target for the treatment of various painful disorders. Several TRPV1 antagonists have been advanced into clinical trials and the initial observations suggest that TRPV1 antagonism may be associated with mild hyperthermia and thermal insensitivity in man. However, no clinical efficacy studies have been described to date, making an assessment of risk:benefit impossible.

Rodent models of persistent pain in drug discovery and development.

The increasing debate regarding the predictiveness of rodent persistent pain models for clinical efficacy has spurred rapidly evolving numbers and types of novel models from which to choose. While several excellent reviews of these models have been published in recent years, few focus on their specific applications and particular challenges with the use of these models in the setting of drug discovery. Thus, in this review, how models of persistent pain may be used to: 1) screen molecules for in vivo efficacy, 2) advance lead compounds and 3) guide decision making for clinical trial design is discussed.

Recent advances in the biology and medicinal chemistry of TRPA1.

The transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is a nonselective cation channel that is highly expressed in small-diameter sensory neurons, where it functions as a polymodal receptor, responsible for detecting potentially harmful chemicals, mechanical forces and temperatures. TRPA1 is also activated and/or sensitized by multiple endogenous inflammatory mediators. As such, TRPA1 likely mediates the pain and neurogenic inflammation caused by exposure to reactive chemicals.

Exploitation and destabilization of a warm, freshwater ecosystem through engineered hydrological change.

Exploitation of freshwater resources is having catastrophic effects on the ecological dynamics, stability, and quality of those water resources on a global scale, especially in arid and semiarid regions. Lake Kinneret, Israel (the Biblical Sea of Galilee), the only major natural freshwater lake in the Middle East, has been transformed functionally into a reservoir over the course of approximately 70 years of hydrological alterations aimed mostly at producing electrical power and increasing domestic and agricultural water supply. Historical changes in lake chemistry and biology were reconstructed using analysis of sedimentary nutrient content, stable and radioisotope composition, biochemical and morphological fossils from algae, remains of aquatic invertebrates, and chemical indices of past light regimes.

Precise and simple optical alignment method for double-sided lithography.

A method for aligning a photolithographic mask at the top of a transparent wafer that has a pattern on its bottom side is presented. The method is based on optical self-imaging of special alignment marks and provides submicrometer accuracy. The method is simple and robust and can conveniently be implemented on laboratory mask aligners for contact or proximity printing.

Compact planar-integrated optical correlator for spatially incoherent signals.

A new, to our knowledge, approach for the planar integration of optical correlators is demonstrated. A VanderLugt-type architecture was used to allow the processing of the spatially incoherent signals of active optoelectronic smart-pixel-device arrays. In a folded optical system all passive components were implemented as a single multiple-phase-level element.