Indole contributes to tetracycline resistance via the outer membrane protein OmpN in Vibrio splendidus

As an interspecies and interkingdom signaling molecule, indole has recently received attention for its diverse effects on the physiology of both bacteria and hosts. In this study, indole increased the tetracycline resistance of Vibrio splendidus. The minimal inhibitory concentration of tetracycline was 10 mu g/mL, and the OD600 of V. splendidus decreased by 94.5% in the presence of 20 mu g/mL tetracycline; however, the OD600 of V. splendidus with a mixture of 20 mu g/mL tetracycline and 125 mu M indole was 10- or 4.5-fold higher than that with only 20 mu g/mL tetracycline at different time points. The percentage of cells resistant to 10 mu g/mL tetracycline was 600-fold higher in the culture with an OD600 of approximately 2.0 (higher level of indole) than that in the culture with an OD600 of 0.5, which also meant that the level of indole was correlated to the tetracycline resistance of V. splendidus. Furthermore, one differentially expressed protein, which was identified as the outer membrane porin OmpN using SDS-PAGE combined with MALDI-TOF/TOF MS, was upregulated. Consequently, the expression of the ompN gene in the presence of either tetracycline or indole and simultaneously in the presence of indole and tetracycline was upregulated by 1.8-, 2.54-, and 6.01-fold, respectively, compared to the control samples. The combined results demonstrated that indole enhanced the tetracycline resistance of V. splendidus, and this resistance was probably due to upregulation of the outer membrane porin OmpN

The development and molecular characterization of muscle spindles from wildtype and mutant mice

Muscle spindles are complex stretch-sensitive mechanoreceptors that consist of 4-12 specialized muscle fibers. These intrafusal muscle fibers are innervated in the central (equatorial) region by an afferent sensory axon and in both peripheral (polar) regions by efferent γ-motoneurons. Until now little is known about muscle spindle development at the molecular level, especially about the development of cholinergic specializations. My study shows that nicotinic acetylcholine receptors (AChR) are concentrated at the γ-motoneuron endplate as well as in the equatorial region. Moreover, enzymes required for the synthesis and removal of acetylcholine, including choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), as well as vesicular acetylcholine transporter (VAChT) and the AChR-associated protein rapsyn are all concentrated at the polar γ-motoneuron endplate and (with the exception of AChE) also at the equatorial region. Finally, the presynaptic protein bassoon, involved in synaptic vesicle exocytosis, is also present at the γ-motoneuron endplate and at the annulospiral sensory nerve ending. During postnatal development, the AChR subunit composition at the γ-motoneuron endplate changes from the γ-subunit containing fetal AChR to the ε-subunit containing adult AChR. This is similar to the postnatal change at the neuromuscular junction. In the equatorial region the ε-subunit expression starts around postnatal week two; however the γ-subunit persists in the central region despite the onset of the ε-subunit expression. Therefore, the γ- and ε-subunits are simultaneously present in the equatorial region. This result was confirmed using a mouse line in which the AChR γ-subunit was genetically labelled by green fluorescence protein (GFP). In this mouse, the GFP-labelled AChR γ-subunits are concentrated at the contact site of the intrafusal fiber with the sensory nerve ending. This result indicates different AChR maturation occurs within two areas of the same intrafusal fiber. I also show that agrin and the agrin receptor complex (consisting of LRP4 and MuSK) are present in muscle spindles in the region of the sensory and motor innervation. Moreover, agrin, MuSK, and LRP4 are expressed by proprioceptive neurons in dorsal root ganglia but only agrin and LRP4 were detected in the cell body of γ-motoneurons in the spinal cord. In mice with a targeted deletion of agrin, AChR aggregates are absent from the polar region and γ-motoneuron endplates do not form. By contrast, AChR aggregates remain detectable in the central part of intrafusal fibers. Moreover, muscle-specific re-expression of mini-agrin is sufficient to restore the formation of synaptic specializations at γ-motoneuron endplates. These results show an unusual AChR maturation at the annulospiral endings and confirm that agrin is a major determinant for the formation of γ-motoneuron endplates. Agrin on the other hand appears dispensable for the aggregation of AChRs in the central region of intrafusal fibers.Muskelspindeln sind komplexe, dehnungsempfindliche Mechanorezeptoren, die aus vier bis zwölf spezialisierten Muskelfasern bestehen. Diese intrafusalen Muskelfasern werden im zentralen (äquatorialen) Bereich durch afferente Axone und in beiden peripheren (polaren) Regionen von efferenten γ-Motoneuronen innerviert. Über die Entwicklung von Muskelspindeln auf molekularer Ebene ist kaum etwas bekannt, vor allem was cholinerge Spezialisierung angeht. In meiner Doktorarbeit konnte ich zeigen, dass nikotinische Azetylcholinrezeptoren (AChR) an der neuromusklären Endplatte von γ-Motoneuronen sowie in der äquatorialen Region konzentriert sind. Auch die Enzyme, die für die Synthese, den Transport und den Abbau von Acetylcholin verantwortlich sind, (Cholinazetyltransferase (ChAT), Azetylcholinesterase (AChE) und vesikuläre Azetylcholintransporter (VAChT) wurden in der polaren und der äquatorialen Region gefunden. Diese Ergebnisse zeigen, dass sowohl die sensorischen afferenten- als auch die motorischen efferenten Neurone im Bereich des Kontaktes mit den Intrafusalfasern cholinerg spezialisiert sind. Während der postnatalen Entwicklung der neuromuskulären Endplatte verändert sich die Zusammensetzung der AChR Untereinheiten. Aus den γ-Untereinheit enthaltenden embryonalen AChRen werden ε-Untereinheit enthaltende adulte AChRen gebildet. Vergleichbare postnatale Veränderungen findet man auch an der neuromuskulären Endplatte der Extrafusalfasern. Im Gegensatz zu diesen Synapsen bleibt in den Intrafusalfasern die Expression der γ-Untereinheit im zentralen Bereich der Nervenfaser neben der Expression der ε-Untereinheit während der postnatalen Entwicklung erhalten. Diese fehlende gamma-zu-epsilon-Umschaltung wurde mit Hilfe von transgenen Mäusen bestätigt, bei denen die AChR γ-Untereinheiten mittels GFP genetisch markiert waren. Diese Ergebnisse zeigen, dass AChR γ-Untereinheiten in adulten intrafusalen Fasern dort konzentriert sind, wo sie Kontakt zu sensorischen Nervenendigungen haben. Agrin und der Agrin Rezeptor-Komplex - bestehend aus MuSK und LRP4 (LDL Rezeptor-beziehend Protein) - konnten in Muskelspindeln im Bereich der sensorischen und motorischen Innervation nachgewiesen werden. Außerdem sind Agrin und sein Rezeptor-Komplex in propriozeptiven Neuronen der Spinalganglien exprimiert, während nur Agrin und LRP4 in γ-Motoneuronen im Rückenmark zu finden sind. In Agrin knock-out Mäusen ist keine AChR Aggregation in der Polarregion zu finden, was zu Defekten in der Ausbildung der gamma-Motoeneuronen Endplatten führt. Im Gegensatz dazu sind die AChR Aggregate im zentralen Teil der intrafusalen Fasern nicht betroffen. Muskelspezifische Überexpression von Mini-Agrin reicht aus, um die Bildung von synaptischen Spezialisierungen in den Endplatten von γ-Motoneuronen wiederherzustellen. Diese Ergebnisse zeigen eine ungewöhnliche AChR Reifung an den annulospiralen sensorischen Endigungen und bestätigen, dass Agrin, ein essenzieller Faktor für die Bildung der Endplatten von γ-Motoneuronen ist, während er nicht notwendig für die Aggregation von AChRs in der zentralen Region von intrafusalen Fasern zu sein scheint

Oxytocin promotes coordinated out-group attack during intergroup conflict in humans

Intergroup conflict contributes to human discrimination and violence, but persists because individuals make costly contributions to their group's fighting capacity. Yet, how group members effectively coordinate their contributions during intergroup conflict remains poorly understood. Here, we examine the role of oxytocin for (the coordination of) contributions to group attack or defense in multi-round, real-time feedback intergroup contests. In a double-blind placebo-controlled study with N = 480 males in Intergroup Attacker-Defender Contests, we found that oxytocin reduced contributions to attack and over time increased attacker's within-group coordination of contributions. However, rather than becoming peaceful, attackers given oxytocin better tracked their rival's historical defense and coordinated their contributions into well-timed and hence more profitable attacks. Our results reveal coordination of contributions as a critical component of successful attacks and subscribe to the possibility that oxytocin enables individuals to contribute to in-group efficiency and prosperity even when doing so implies outsiders are excluded or harmed. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). Keywords: collective contribution; group coordination; human; intergroup conflict; neuroscience; out-group attack; oxytocin

Culture Condition Effect on Bioflocculant Production and Actual Wastewater Treatment Application by Different Types of Bioflocculants

The effect of culture condition on different types of bioflocculant production and its application on actual wastewater treatment were studied in this chapter. The advantages of mixed strain HXJ-1 were as follows: directly using acidic wine wastewater, adapting to wastewater at high concentrations and the presence of less nitrogen. HXJ-1 achieved good flocculating rate when the chemical oxygen demand (COD) was 12,000 mg/L, C/N 20:1. Three kinds of bioflocculants had some good treatment results on starch wastewater, printing and dyeing wastewater and landfill leachate. The treatment effect of XJBF-1 (produced by mixed strain HXJ-1) on the starch wastewater was better than that of traditional polyacrylamide and other bioflocculants produced by a single bacterial (X15BF-1) and yeast strain (J1BF-1). XJBF-1 had better treatment results on three types of wastewater. It also had good removal rate of chromaticity, especially on the starch wastewater , the printing and dyeing wastewater; the removal rate was up to 88%, and the starch wastewater COD removal rate was up to 86%

The anti-tumor histone deacetylase inhibitor SAHA and the natural flavonoid curcumin exhibit synergistic neuroprotection against amyloid-beta toxicity

With the trend of an increasing aged population worldwide, Alzheimer’s disease (AD), an age-related neurodegenerative disorder, as one of the major causes of dementia in elderly people is of growing concern. Despite the many hard efforts attempted during the past several decades in trying to elucidate the pathological mechanisms underlying AD and putting forward potential therapeutic strategies, there is still a lack of effective treatments for AD. The efficacy of many potential therapeutic drugs for AD is of main concern in clinical practice. For example, large bodies of evidence show that the antitumor histone deacetylase (HDAC) inhibitor, suberoylanilidehydroxamic acid (SAHA), may be of benefit for the treatment of AD; however, its extensive inhibition of HDACs makes it a poor therapeutic. Moreover, the natural flavonoid, curcumin, may also have a potential therapeutic benefit against AD; however, it is plagued by low bioavailability. Therefore, the integrative effects of SAHA and curcumin were investigated as a protection against amyloid-beta neurotoxicity in vitro. We hypothesized that at low doses their synergistic effect would improve therapeutic selectivity, based on experiments that showed that at low concentrations SAHA and curcumin could provide comprehensive protection against Ab25–35-induced neuronal damage in PC12 cells, strongly implying potent synergism. Furthermore, network analysis suggested that the possible mechanism underlying their synergistic action might be derived from restoration of the damaged functional link between Akt and the CBP/p300 pathway, which plays a crucial role in the pathological development of AD. Thus, our findings provided a feasible avenue for the application of a synergistic drug combination, SAHA and curcumin, in the treatment of AD