The effects of nonlocality on the evolution of higher order fluxes in non-equilibrium thermodynamics

The role of gradient dependent constitutive spaces is investigated on the example of Extended Thermodynamics of rigid heat conductors. Different levels of nonlocality are developed and the different versions of extended thermodynamics are classified. The local form of the entropy density plays a crucial role in the investigations. The entropy inequality is solved under suitable constitutive assumptions. Balance form of evolution equations is obtained in special cases. Closure relations are derived on a phenomenological level.Comment: 16 pages, 1 figur

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

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

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

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event