67 research outputs found
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
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