Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location

Necrotizing Fasciitis Due to Streptococcus pneumoniae after Intramuscular Injection of Nonsteroidal Anti-Inflammatory Drugs: Report of 2 Cases and Review

Two cases of pneumococcal necrotizing fasciitis (NF) occurred after intramuscular injections of nonsteroidal anti-inflammatory drugs; another 5 cases reported in the literature fulfilled the criteria for NF involving Streptococcus pneumoniae. Conditions associated with alterations of immune function could be identified in 6 of the 7 cases; 2 patients died despite surgical and antimicrobial treatmen

The Effect of Ketoconazole on Amphotericin B in a Model of Disseminated Aspergillosis

The potential of ketoconazole prophylaxis to antagonize the activity of amphotericin B against aspergilli was investigated in vitro and in neutropenic mice. Exposure of Aspergillus fumigatus (six strains) and of Aspergillus flavus or Aspergillus niger to ketoconazole resulted in a uniform increase of the minimal fungicidal activity of amphotericin B, from 0.15-0.63 mg/liter to >2.5 mg/liter in a microwell assay. To test the relevance of this antagonism in vivo, we challenged neutropenic mice iv with a lethal dose of conidia from two strains of A. fumigatus and then treated the mice first with ketoconazole and then with amphotericin B or amphotericin B plus ketoconazole. Pretreatment with ketoconazole for 48 hr completely abolished the protective effect of a subsequent therapy with amphotericin B, whether ketoconazole therapy was stopped (P < .001) or not (P <.001). Ketoconazole given alone had no significant effect on survival. Our data show that ketoconazole not only antagonized the fungicidal activity of amphotericin B in vitro but also abolished in vivo the protective effect of the only drug shown to be useful in the therapy of aspergillosis. The clinical importance of this antagonism, which is not limited to Aspergilli in vitro, requires careful consideration before ketoconazole prophylaxis can be recommended for patients at high risk of developing invasive opportunistic fungal infection

Metabolic network capacity of Escherichia coli for Krebs cycle-dependent proline hydroxylation

Figure S1. Physiology of recombinant E. coli BL21(DE3)(pLysS) strains bearing pET-24a. Panel A and B show biomass formation (circles), glucose consumption (squares), acetate formation (triangles), and proline consumption (diamonds) during batch cultivation of wildtype (closed symbols) and ΔputA (open symbols) strains at 30°C in M9 medium supplemented with 5 g L−1 glucose in the absence (A) or presence (B) of 5 mM proline, respectively. Figure S2. SDS-PAGE analysis of recombinant E. coli BL21(DE3)(pLysS) (pET_p4h1of) and E. coli BL21 ΔputA (DE3) (pLysS) (pET_p4h1of) at different time points during growth in M9 medium with 5 g L−1 glucose (glc) only or with addition of 5 mM proline (pro) at 30°C. M: protein size marker. Figure S3. Physiology of recombinant E. coli BL21(DE3)(pLysS) strains bearing pET_p4h1of. Biomass formation (circles), glucose consumption (squares), acetate formation (triangles), hyp formation (stars), and proline consumption (diamonds) during batch cultivation of wildtype (closed symbols) and ΔputA (open symbols) strains are shown. Cultivation was performed at 30°C in M9 medium supplemented with 5 g L−1 glucose in the absence (panel A) or presence of 5 mM proline (panels B and C). Table S4. Mass isotopomer distribution of alanine for the wt_pET strain at 30°C in M9 medium supplemented with 5 g L−1 U-13C labeled glucose in the absence or presence of 5 mM proline. Table S5. Reactions of the central carbon metabolism generating or consuming NTP and/or redox equivalents. Table S6. Bacterial strains and plasmids used in this study. Table S7. Correlation factors between OD600 1 and cell dry weight concentration (gCDW L−1) of the strains used in this study

Calcium Dynamics in Basal Dendrites of Layer 5A and 5B Pyramidal Neurons Is Tuned to the Cell-Type Specific Physiological Action Potential Discharge

Layer 5 (L5) is a major neocortical output layer containing L5A slender-tufted (L5A-st) and L5B thick-tufted (L5B-tt) pyramidal neurons. These neuron types differ in their in vivo firing patterns, connectivity and dendritic morphology amongst other features, reflecting their specific functional role within the neocortical circuits. Here, we asked whether the active properties of the basal dendrites that receive the great majority of synaptic inputs within L5 differ between these two pyramidal neuron classes. To quantify their active properties, we measured the efficacy with which action potential (AP) firing patterns backpropagate along the basal dendrites by measuring the accompanying calcium transients using two-photon laser scanning microscopy in rat somatosensory cortex slices. For these measurements we used both “artificial” three-AP patterns and more complex physiological AP patterns that were previously recorded in anesthetized rats in L5A-st and L5B-tt neurons in response to whisker stimulation. We show that AP patterns with relatively few APs (3APs) evoke a calcium response in L5B-tt, but not L5A-st, that is dependent on the temporal pattern of the three APs. With more complex in vivo recorded AP patterns, the average calcium response was similar in the proximal dendrites but with a decay along dendrites (measured up to 100 μm) of L5B-tt but not L5A-st neurons. Interestingly however, the whisker evoked AP patterns—although very different for the two cell types—evoke similar calcium responses. In conclusion, although the effectiveness with which different AP patterns evoke calcium transients vary between L5A-st and L5B-tt cell, the calcium influx appears to be tuned such that whisker-evoked calcium transients are within the same dynamic range for both cell types

Spiritual Dryness as a Measure of a Specific Spiritual Crisis in Catholic Priests: Associations with Symptoms of Burnout and Distress

Spirituality/religiosity is recognized as a resource to cope with burdening life events and chronic illness. However, less is known about the consequences of the lack of positive spiritual feelings. Spiritual dryness in clergy has been described as spiritual lethargy, a lack of vibrant spiritual encounter with God, and an absence of spiritual resources, such as spiritual renewal practices. To operationalize experiences of ``spiritual dryness'' in terms of a specific spiritual crisis, we have developed the ``spiritual dryness scale'' (SDS). Here, we describe the validation of the instrument which was applied among other standardized questionnaires in a sample of 425 Catholic priests who professionally care for the spiritual sake of others. Feelings of ``spiritual dryness'' were experienced occasionally by up to 40%, often or even regularly by up to 13%. These experiences can explain 44% of variance in daily spiritual experiences, 30% in depressive symptoms, 22% in perceived stress, 20% in emotional exhaustion, 19% in work engagement, and 21% of variance of ascribed importance of religious activity. The SDS-5 can be used as a specific measure of spiritual crisis with good reliability and validity in further studies

Size dependent deformation of beta brass

Previous research has shown that size scale dictates materials strength, reaching into the GPa range for specimens in the (sub-) micron regime. However, the influence of crystal structure on this ‘size-effect’ is poorly understood. In the present work, the deformation behavior of beta brass, which has a CsCl (B2) crystal structure and a low thermal component to the room temperature strength, has been studied through the compression of focused ion beam manufactured pillars at room temperature. The size dependence of beta brass is found to be close to that observed in FCC metals although the deformation processes differ significantly. While its dislocation behavior resembles that of FCC metals, its slip behavior is typical of BCC metals. Furthermore, the crystal orientation dependence of the yield strength shows a shift as sample size decreases. These findings are discussed in the context of the mobility of screw dislocations as well as surface dislocation nucleation, which might promote such a change in orientation dependence