פרסומים

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor alpha (VEGF-alpha) by a minor subset of activated EpCAM(+)CD59(+)Ly-6D(+) cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guerin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.

A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient's leg did not have to be amputated and he is undergoing rehabilitation.

Given that causative linguistic constructions are divisible into three parts: i) a cause (c); ii) an effect (e); and iii) the dependency (D) between (c) and (e), in studying the nature of (D), one should examine whether a one, all-encompassing, causative meaning component underlying the diverse linguistic phenomena is a justifiable position, or rather different ones should be distinguished for the various causative constructions. Only recently several philosophers argued in favor of theories of causal pluralism, allowing the co-existence of different notions of causation; some cognitive studies also indicate that people have a pluralistic conception of causation, similarly it has been proposed that the semantic content of (D) is different in various constructions, tracing whether the main verb encodes a necessary or a sufficient condition. This paper expands on this latter line of thought by focusing on the types of dependencies encoded within three verbal constructions in Hebrew, considering crucially whether these dependencies are asserted and/or presupposed. It argues, therefore, in favor of a non-unified semantic analysis for (D) denoted by the three verbal causative constructions to be passed under review here: overt causatives, verbs of change of state and caused activity verbs. According to the current proposal: Overt causatives assert necessary conditions;  change of states causatives assert necessary conditions and presuppose potential sufficient conditions; and Caused activities only presuppose potential sufficient conditions.

Controlling Ae. aegypti populations and the prevention of mosquito bites includes the development of monitoring, repelling and attract-and-kill strategies that are based on understanding the chemical ecology of these pests. Olfactory-mediated attraction to mammals has recently been linked to the mosquito Aedes aegypti odorant receptor Or4, which is activated by animal-released 6-Methyl-5-hepten-2-one (sulcatone). This odorant is also a major component of flower scents and may play a role outside animal-host seeking. To explore the role of this chemical cue, we looked at the interaction between sulcatone and an Or4 homolog expressed in the antennae of the strict nectar-feeding mosquito Toxorhynchites amboinensis. Using the two-electrode voltage clamp of Xenopus oocytes as a heterologous expression system, we show that this receptor is a high intensity sulcatone receptor comparable to its Aedes counterparts. We also show that OR4 is activated by other aliphatic ketones and is inhibited by DEET. This pharmacological characterization suggests that sulcatone may be operating in more than one context in the Culicidae family.

A sulfation-controlled binding of heavy metal ions to glycans was realized using electrochemical analysis. The artwork presents glassy carbon electrodes modified by a series of hyaluronans with similar sizes but different sulfation patterns. The binding of heavy metal ions to these surfaces resulted in changes of the layer density that produced impedimetric response. The impedimetric response revealed that the selectivity of the hyaluronans to a specific metal ion depends on their sulfation pattern. More information can be found in the Full Paper by J. Rademann, S. Yitzchaik, M. Hurevich, et al. (DOI: 10.1002/chem.201901538).

 

Volatile and gas phase organic sulfur compounds (VOSCs) are important components in subsurface reservoir fluids and despite their relatively low concentrations, can provide important information about organic matter origin, diagenetic transformation, thermal maturation, and oil and gas generation, expulsion, and migration. We present an approach for the utilization of VOSC concentration and compound specific S isotopes ratio (δ34S) data as a new geochemical tool to study natural gas origin and formation. We studied the formation pathways of VOSCs, their δ34S values, and interaction with an organic-rich sedimentary rock (or ‘source rock’) from the Ghareb Formation (Type II-S kerogen) deposited in an upwelling marine environment. The immature source rock was subjected to laboratory controlled thermal maturation. We used a semi-open, non-isothermal pyrolysis system heated between 200 and 440 °C, and analyzed the molecular composition and compound specific δ34S values of the evolved gases at various thermal maturity stages. Formation of VOSCs commenced at 206 °C, a temperature generally associated with less thermally mature systems, and typically before the onset of oil generation for similar organic-rich source rocks, allowing study of low thermal maturity conditions (∼0.3 %Roeq). Overall, the VOSCs obtained had δ34S values similar to the bulk kerogen values (mostly within 4‰). However, thiol (or mercaptan) δ34S values closely followed those of H2S (Δ34Sthiols-H2S = −1 ± 1‰) throughout the experiment. Ab-initio calculations for the S isotopic exchange between H2S and thiols were close to the experimental observations. This suggests that thiols rapidly attained equilibrium with H2S despite their very short residence time in the system (minutes to hours). Furthermore, throughout the experiment, the concentrations of the six different thiols were found to be proportional to the coexisting, concentration ratio of [H2]/[H2S]. The proportionality factors of the 6 different thiols strongly correlate with reported heats of formation (ΔHf°), further supporting the notion that the generation of thiols in the system rapidly reached equilibrium. At pyrolysis temperatures up to 350 °C, δ34S and concentration values of other VOSCs produced in the gas phase, including sulfides and thiophenes, probably represent generation from S-containing moieties in kerogen and bitumen with limited interaction with co-existing H2S. The reaction of hydrocarbons and H2S to produce VOSCs is inversely correlated with thermal stability, i.e. thiols > sulfides > thiophenes. Therefore, the δ34S values, concentrations and distributions of VOSCs can be utilized as a proxy for reaction extent and formation mechanism of petroleum and H2S, including primary generation by thermal maturation, or potentially other processes such as migration and thermochemical sulfate reduction. This work demonstrates a novel and useful geochemical tool to study the source and fate of natural gas in the subsurface. © 2019 Elsevier Ltd

The Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV) took place in Madrid, Spain from May 13th to 16th 2018. Again, presentations on new medical devices and neuromodulation and discussions on device-related regulatory aspects were included in the programme. The virtual special issue on "neuromodulation" summarises the presentations focusing firstly, on the pre-clinical developments and the difficulties of clinical trial designs for neuromodulatory therapies, including vagus nerve stimulation (VNS) and Brain-Responsive Neurostimulation (RNS), and the use of transcutaneous vagus nerve stimulation (tVNS) as a potential screening tool for determining the efficacy of neuromodulatory treatments in individual patients; secondly, on wearable devices for seizure monitoring through indices of peripheral sympathetic nervous activity, the use of such devices in combination with biofeedback for the treatment of epilepsy, and its potential for improving epilepsy specialist services, particularly in remote areas.

Mosquitoes exhibit highly diverse and fast evolving odorant receptors. The indole-sensitive odorant receptor gene clade, comprised of Or2 and Or10 is a notable exception on account of its conservation in both mosquito subfamilies. This group of paralogous genes exhibits a complex developmental expression pattern in Aedes aegypti: AaegOr2 is expressed in both adults and larvae, AaegOr10 is adult-specific and a third member named AaegOr9 is larva-specific. OR2 and OR10 have been deorphanized and are selectively activated by indole and skatole, respectively. Using the two-electrode voltage clamp of Xenopus oocytes expressing Ae. aegypti ORs, we show that AaegOR9 is supersensitive and narrowly tuned to skatole. Our findings suggest that Ae. aegypti has evolved two distinct molecular strategies to detect skatole in aquatic and terrestrial environments, highlighting the central ecological roles of indolic compounds in the evolutionary and life histories of these insects.

The initiation of contact between liquid and a dry solid is of great fundamental and practical importance. We experimentally probe the dynamics of wetting that occur when an impacting drop first contacts a dry surface. We show that, initially, wetting is mediated by the formation and growth of nanoscale liquid bridges, binding the liquid to the solid across a thin film of air. As the liquid bridge expands, air accumulates and deforms the liquid-air interface, and a capillary wave forms ahead of the advancing wetting front. This capillary wave regularizes the pressure at the advancing wetting front and explains the anomalously low wetting velocities observed. As the liquid viscosity increases, the wetting front velocity decreases; we propose a phenomenological scaling for the observed decrease of the wetting velocity with liquid viscosity.

Enterococcus faecalis is the most commonly recovered species from failed root canal treatments. In this study, we tested the capability of a novel intracanal sustained-release filler (SRF) containing cetylpyridinium chloride (CPC) to disinfect dentinal tubules of segmented human tooth specimens. Human dental root specimens were infected with E. faecalis V583 for 3 weeks in a static environment. The tested intracanal medicaments were SRF-CPC and calcium hydroxide (CH). Each medicament was introduced into the canal of the dental specimen and incubated for 7 days. The bacteriological samples were taken by shaving the dentine surrounding the root canal with dental burs ranging in size from ISO 014-020. The obtained dentine powder was collected in test tubes containing phosphate-buffered saline, sonicated, and plated on agar plates. Colony-forming units were counted after 48 h of incubation. Random specimens were also examined under confocal laser scanning microscopy and scanning electron microscopy. A statistical difference was found in the bacterial counts obtained from all layers of infected dentin between the control and the SRF-CPC groups. CH reduced bacterial viability significantly only in the first layer of the infected dentin, up to 150 $μ$m into the dentinal tubules. CLSM images showed that SRF-CPC killed most bacteria throughout the infected dentin up to 700 $μ$m of penetration. SEM images demonstrated the adhesion ability of SRF-CPC to the dentinal wall. In conclusion, SRF-CPC is a potential intracanal medicament for disinfecting dentinal tubules.

Microbial associations are widespread across the insects. In the olive fruit fly Bactrocera oleae (Diptera: Tephritidae), vertically transmitted gut symbionts contribute to larval development inside the olive host, and to adult nutrition. Nevertheless, their effect on behavioural decisions of adults is unknown. In this study, we show that symbiotic bacteria affect oviposition behaviour in B. oleae. We studied the effect of different fruits as hosts and different gut-bacteria as gut-symbionts on oviposition attempts and fly development in B. oleae. Untreated flies that had native gut-symbionts attempted oviposition significantly more times than axenic flies as well as flies treated with medfly-associated Pantoea or Klebsiella bacteria. Axenic flies provided with a diet containing the homogenized gut of symbiotic flies recovered the same number of oviposition attempts as their symbiotic counterparts. As for as the different hosts, green olives (unripe) and grapes were preferred while black olives (ripe) elicited the least number of oviposition attempts, with an interactive effect of host and bacterial treatments. It appears that both the host attributes and the native gut-symbionts drive oviposition preference towards green olives in B. oleae. Moreover, both bacterial treatments and hosts significantly affected the development of B. oleae larvae. Though grapes elicited as many oviposition attempts as green olives, they yielded no pupae. Taken together, our results suggest that the intimate association between B. oleae and their gut-microbes, extends beyond nutritional support to behaviour.