dUTPase based switch controls transfer of virulence genes in order to preserve integrity of the transferred mobile genetic elements

dUTPases ubiquitously regulate cellular dUTP levels to preserve genome integrity. Recently, several other cellular processes were reported to be controlled by dUTPases including the horizontal transfer of Staphylococcus aureus pathogenicity islands (SaPI). SaPIs are mobil genetic elements that encode virulence enhancing factors e.g. toxins. Here, phage dUTPases were proposed to counteract the repressor protein (Stl) and promote SaPI excision and transfer. A G protein-like mechanism was proposed which is unexpected in light of the kinetic mechanism of dUTPase. Here we investigate the molecular mechanism of SaPI transfer regulation, using numerous dUTPase variants and a wide range of in vitro methods (steady-state and transient kinetics, VIS and fluorescence spectroscopy, EMSA, quartz crystal microbalance, X-ray crystallography). Our results unambiguously show that Stl inhibits the enzymatic activity of dUTPase in the nM concentration range and dUTP strongly inhibits the dUTPase: Stl complexation. These results identify Stl as a highly potent dUTPase inhibitor protein and disprove the G protein-like mechanism. Importantly, our results clearly show that the dUTPase:dUTP complex is inaccessible to the Stl repressor. Unlike in small GTPases, hydrolysis of the substrate nucleoside triphosphate (dUTP in this case) is required prior to the interaction with the partner (Stl repressor in this case). We propose that dUTPase can efficiently interact with Stl and induce SaPI excision only if the cellular dUTP level is low (i.e. when dUTPase resides mainly in the apo enzyme form) while high dUTP levels would inhibit SaPI transfer. This mechanism may serve the preservation of the integrity of the transferred SaPI genes and links the well-known metabolic role of dUTPases to their newly revealed regulatory function in spread of virulence factors

Covariant description of kinetic freeze out through a finite time-like layer

The Freeze Out (FO) problem is addressed for a covariant FO probability and a finite FO layer with a time-like normal vector continuing the line of studies introduced in Ref. [1]. The resulting post FO momentum distribution functions are presented and discussed. We show that in general the post FO distributions are non-thermal and asymmetric distributions even for time-like FO situations.Comment: 10 pages, 12 figures, major rewrite with changed content, corrected typos and new references adde

Covariant description of kinetic freeze out through a finite space-like layer

The problem of Freeze Out (FO) in relativistic heavy ion reactions is addressed. We develop and analyze an idealized one-dimensional model of FO in a finite layer, based on the covariant FO probability. The resulting post FO phase-space distributions are discussed for different FO probabilities and layer thicknesses.Comment: 16 pages, 19 figures, changed content, references adde

Impact of Nucleon Mass Shift on the Freeze Out Process

The freeze out of a massive nucleon gas through a finite layer with time-like normal is studied. The impact of in-medium nucleon mass shift on the freeze out process is investigated. A considerable modification of the thermodynamical variables temperature, flow-velocity, energy density and particle density has been found. Due to the nucleon mass shift the freeze out particle distribution functions are changed noticeably in comparison with evaluations, which use vacuum nucleon mass.Comment: submitted to Physical Review

Variational and Potential Formulation for Stochastic Partial Differential Equations

There is recent interest in finding a potential formulation for Stochastic Partial Differential Equations (SPDEs). The rationale behind this idea lies in obtaining all the dynamical information of the system under study from one single expression. In this Letter we formally provide a general Lagrangian formalism for SPDEs using the Hojman et al. method. We show that it is possible to write the corresponding effective potential starting from an s-equivalent Lagrangean, and that this potential is able to reproduce all the dynamics of the system, once a special differential operator has been applied. This procedure can be used to study the complete time evolution and spatial inhomogeneities of the system under consideration, and is also suitable for the statistical mechanics description of the problem. Keywords: stochastic partial differential equations, variational formulation, effective potential. PACS: 45.20.Jj; 02.50.-r; 02.50.Ey.Comment: Letter, 4 pages, no figures; v2: references added, minor change

Differential Roles of the Two Raphe Nuclei in Amiable Social Behavior and Aggression – An Optogenetic Study

Serotonergic mechanisms hosted by raphe nuclei have important roles in affiliative and agonistic behaviors but the separate roles of the two nuclei are poorly understood. Here we studied the roles of the dorsal (DR) and median raphe region (MRR) in aggression by optogenetically stimulating the two nuclei. Mice received three 3 min-long stimulations, which were separated by non-stimulation periods of 3 min. The stimulation of the MRR decreased aggression in a phasic-like manner. Effects were rapidly expressed during stimulations, and vanished similarly fast when stimulations were halted. No carryover effects were observed in the subsequent three trials performed at 2-day intervals. No effects on social behaviors were observed. By contrast, DR stimulation rapidly and tonically promoted social behaviors: effects were present during both the stimulation and non-stimulation periods of intermittent stimulations. Aggressive behaviors were marginally diminished by acute DR stimulations, but repeated stimulations administered over 8 days considerably decreased aggression even in the absence of concurrent stimulations, indicating the emergence of carryover effects. No such effects were observed in the case of social behaviors. We also investigated stimulation-induced neurotransmitter release in the prefrontal cortex, a major site of aggression control. MRR stimulation rapidly but transiently increased serotonin release, and induced a lasting increase in glutamate levels. DR stimulation had no effect on glutamate, but elicited a lasting increase of serotonin release. Prefrontal serotonin levels remained elevated for at least 2 h subsequent to DR stimulations. The stimulation of both nuclei increased GABA release rapidly and transiently. Thus, differential behavioral effects of the two raphe nuclei were associated with differences in their neurotransmission profiles. These findings reveal a surprisingly strong behavioral task division between the two raphe nuclei, which was associated with a nucleus-specific neurotransmitter release in the prefrontal cortex

Evolutionary and socio-cultural influences on feelings and attitudes towards nature: a cross-cultural study

Mounting environmental issues have prompted reconsideration of the human–nature relationship. Accordingly, attitudes to nature, as an important dimension of human–nature interactions, have become a research focus. How feelings and attitudes towards nature are influenced by evolutionary and social-cultural constructions, and whether there is variation between different cultural groups, demands more attention. Using a survey of visitors to two very different National Parks, the New Forest National Park, England and Jiuzhaigou Scenic Area, China, this paper shows that of nationality and living environment, differences between the two nationalities were significant in respect of both attitudes and feelings. Specifically, it demonstrates that the biophilia thesis, which purports that people have an innate and a genetically inherited need for affiliation with nature, is influenced by their socio-cultural environment, in particular their national culture, but also by their current living place. The study contributes to our understanding of sustainable tourism in natural areas

Median raphe region stimulation alone generates remote, but not recent fear memory traces

The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted electric shocks with optic stimulation of MRR in C57BL/6N male mice in an optogenetic conditioning paradigm and found that stimulations produced agitation, but not fear, during the conditioning trial. Contextual fear, reflected by freezing was not present the next day, but appeared after a 7 days incubation. The optogenetic silencing of MRR during electric shocks ameliorated conditioned fear also seven, but not one day after conditioning. The optogenetic stimulation patterns (50Hz theta burst and 20Hz) used in our tests elicited serotonin release in vitro and lead to activation primarily in the periaqueductal gray examined by c-Fos immunohistochemistry. Earlier studies demonstrated that fear can be induced acutely by stimulation of several subcortical centers, which, however, do not generate persistent fear memories. Here we show that the MRR also elicits fear, but this develops slowly over time, likely by plastic changes induced by the area and its connections. These findings assign a specific role to the MRR in fear learning. Particularly, we suggest that this area is responsible for the durable sensitization of fear circuits towards aversive contexts, and by this, it contributes to the persistence of fear memories. This suggests the existence a bottom-up control of fear circuits by the MRR, which complements the top-down control exerted by the medial prefrontal cortex