Selectivity of adaptation in single units: implications for FMRI experiments

Understanding the neural basis of adaptation (repetition suppression) is critical for interpreting fMRI-adaptation experiments. Sawamura and colleagues provide a critical stepping-stone by elucidating the relation between neural adaptation and response selectivity. They find some cross-adaptation by two different stimuli that activate the same neuron.     

Seeing invisible motion: a human FMRI study

A common view about visual consciousness is that it could arise when and where activity reaches some higher level of processing along the cortical hierarchy. Reports showing that activity in striate cortex can be dissociated from awareness , whereas the latter modulates activity in higher areas , point in this direction. In the specific case of visual motion, a central, "perceptual" role has been assigned to area V5: several human and monkey studies have shown V5 activity to correlate with the motion percept. Here we show that activity in this and other higher cortical areas can be also dissociated from perception and follow the physical stimulus instead. The motion information in a peripheral grating modulated fMRI responses, despite being invisible to human volunteers: under crowding conditions , areas V3A, V5, and parietal cortex still showed increased activity when the grating was moving compared to when it was flickering. We conclude that stimulus-specific activation of higher cortical areas does not necessarily result in awareness of the underlying stimulus.     

Hydrophobic interaction chromatography selectivity changes among three stable proteins: conformation does not play a major role

Interesting retention and selectivity changes have been noted for a number of proteins in hydrophobic interaction chromatography (HIC). In this study, we investigated the degree to which conformational changes may be responsible for selectivity changes of stable proteins. Hydrogen-deuterium isotope exchange detected by mass spectrometry was used to investigate changes in solvent accessibility during adsorption on HIC media. Lysozyme was determined to exhibit EX2 hydrogen exchange kinetics both in solution and adsorbed to Butyl Sepharose 4 Fast Flow and Phenyl Sepharose 6 Fast Flow high sub surfaces. A small, but significant, increase in solvent accessibility was observed upon adsorption. Similar approaches were used to analyze solvent accessibility of three stable proteins with melting temperatures above 50 degrees C exhibiting significant selectivity changes on Butyl Sepharose and Toyopearl Butyl 650M. While all three proteins (lysozyme, chymotrypsinogen A, and ovalbumin) exhibited enhanced exchange while adsorbed, no differences in solvent accessibility on the different adsorbents were observed. More detailed studies of lysozyme showed no significant changes in labeling prior or during elution. These results demonstrate that HIC surfaces examined here do not dramatically alter the structure of these stable proteins and that differences in conformation are not responsible for the selectivity changes observed. Thus, other factors such as different preferred binding orientations or variations between the media pore structure, size, and/or surface chemistry must be responsible.     

Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study

IntroductionVagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarce. Transvenous VNS (tVNS) is a newly developed and less invasive method to stimulate the vagus nerve. In the present study, we determined whether tVNS is a feasible and safe procedure and investigated its putative anti-inflammatory effects during experimental human endotoxemia.MethodsWe performed a randomized double-blind sham-controlled study in healthy male volunteers. A stimulation catheter was inserted in the left internal jugular vein at spinal level C5–C7, adjacent to the vagus nerve. In the tVNS group (n = 10), stimulation was continuously performed for 30 minutes (0–10 V, 1 ms, 20 Hz), starting 10 minutes before intravenous administration of 2 ng kg⁻¹Escherichia coli lipopolysaccharide (LPS). Sham-instrumented subjects (n = 10) received no electrical stimulation.ResultsNo serious adverse events occurred throughout the study. In the tVNS group, stimulation of the vagus nerve was achieved as indicated by laryngeal vibration. Endotoxemia resulted in fever, flu-like symptoms, and hemodynamic changes that were unaffected by tVNS. Furthermore, plasma levels of inflammatory cytokines increased sharply during endotoxemia, but responses were similar between groups. Finally, cytokine production by leukocytes stimulated with LPS ex vivo, as well as neutrophil phagocytosis capacity, were not influenced by tVNS.ConclusionstVNS is feasible and safe, but does not modulate the innate immune response in humans in vivo during experimental human endotoxemia.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01944228","term_id":"NCT01944228"}}NCT01944228. Registered 12 September 2013.     

Abnormal FMRI adaptation to unfamiliar faces in a case of developmental prosopamnesia

In rare cases, damage to the temporal lobe causes a selective impairment in the ability to learn new faces, a condition known as prosopamnesia [1]. Here we present the case of an individual with prosopamnesia in the absence of any acquired structural lesion. "C" shows intact processing of simple and complex nonface objects, but her ability to learn new faces is severely impaired. We used a neural marker of perceptual learning known as repetition suppression to examine functioning within C's fusiform face area (FFA), a region of cortex involved in face perception [2]. For comparison, we examined repetition suppression in the scene-selective parahippocampal place area (PPA) [3]. As expected, normal controls showed significant region-specific attenuation of neural activity across repetitions of each stimulus class. C also showed normal attenuation within the PPA to familiar and unfamiliar scenes, and within the FFA to familiar faces. Critically, however, she failed to show any adaptive change within the FFA for repeated unfamiliar faces, despite a face-specific blood-oxygen-dependent response (BOLD) response in her FFA during viewing of face stimuli. Our findings suggest that in developmental prosopamnesia, the FFA cannot maintain stable representations of new faces for subsequent recall or recognition.     

Vasopressin does not enhance memory processes: a study in human twins

Behavioral effects of lysin-vasopressin (LVP) were investigated applying two paradigms from human experimental psychology. The first task was designed to simulate amnesic symptoms in normals. The second task addressed the emotional value of the items to be processed. Additionally, EEG recordings were used as indicators of the central nervous system effectiveness of LVP. Blood pressure and heart rate measured peripheral arousal. The co-twin control method was employed to increase experimental power. Contrary to the prediction of the vasopressin memory hypothesis none of the specific memory parameters was improved by LVP treatment. Changes in the electrical activity of the brain, but not in blood pressure and heart rate indicated central nervous system actions of LVP. However, interpretation of LVP effects in terms of memory processing seems not to be justified.     

Role of spike-frequency adaptation in shaping neuronal response to dynamic stimuli

Spike-frequency adaptation is the reduction of a neuron’s firing rate to a stimulus of constant intensity. In the locust, the Lobula Giant Movement Detector (LGMD) is a visual interneuron that exhibits rapid adaptation to both current injection and visual stimuli. Here, a reduced compartmental model of the LGMD is employed to explore adaptation’s role in selectivity for stimuli whose intensity changes with time. We show that supralinearly increasing current injection stimuli are best at driving a high spike count in the response, while linearly increasing current injection stimuli (i.e., ramps) are best at attaining large firing rate changes in an adapting neuron. This result is extended with in vivo experiments showing that the LGMD’s response to translating stimuli having a supralinear velocity profile is larger than the response to constant or linearly increasing velocity translation. Furthermore, we show that the LGMD’s preference for approaching versus receding stimuli can partly be accounted for by adaptation. Finally, we show that the LGMD’s adaptation mechanism appears well tuned to minimize sensitivity for the level of basal input. This article is part of a special issue on Neuronal Dynamics of Sensory Coding.     

Fast adaptation in mouse olfactory sensory neurons does not require the activity of phosphodiesterase

Vertebrate olfactory sensory neurons rapidly adapt to repetitive odorant stimuli. Previous studies have shown that the principal molecular mechanisms for odorant adaptation take place after the odorant-induced production of cAMP, and that one important mechanism is the negative feedback modulation by Ca2+-calmodulin (Ca2+-CaM) of the cyclic nucleotide-gated (CNG) channel. However, the physiological role of the Ca2+-dependent activity of phosphodiesterase (PDE) in adaptation has not been investigated yet. We used the whole-cell voltage-clamp technique to record currents in mouse olfactory sensory neurons elicited by photorelease of 8-Br-cAMP, an analogue of cAMP commonly used as a hydrolysis-resistant compound and known to be a potent agonist of the olfactory CNG channel. We measured currents in response to repetitive photoreleases of cAMP or of 8-Br-cAMP and we observed similar adaptation in response to the second stimulus. Control experiments were conducted in the presence of the PDE inhibitor IBMX, confirming that an increase in PDE activity was not involved in the response decrease. Since the total current activated by 8-Br-cAMP, as well as that physiologically induced by odorants, is composed not only of current carried by Na+ and Ca2+ through CNG channels, but also by a Ca2+-activated Cl- current, we performed control experiments in which the reversal potential of Cl- was set, by ion substitution, at the same value of the holding potential, -50 mV. Adaptation was measured also in these conditions of diminished Ca2+-activated Cl- current. Furthermore, by producing repetitive increases of ciliary's Ca2+ with flash photolysis of caged Ca2+, we showed that Ca2+-activated Cl- channels do not adapt and that there is no Cl- depletion in the cilia. All together, these results indicate that the activity of ciliary PDE is not required for fast adaptation to repetitive stimuli in mouse olfactory sensory neurons.     

High larval density does not induce a prophylactic immune response in a butterfly

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Obesity does not aggravate vitrification injury in mouse embryos: a prospective study

ABSTRACT: BACKGROUND: Obesity is associated with poor reproductive outcomes, but few reports have examined thawed embryo transfer in obese women. Many studies have shown that increased lipid accumulation aggravates vitrification injury in porcine and bovine embryos, but oocytes of these species have high lipid contents (63 ng and 161 ng, respectively). Almost nothing is known about lipids in human oocytes except that these cells are anecdotally known to be relatively lipid poor. In this regard, human oocytes are considered to be similar to those of the mouse, which contain approximately 4 ng total lipids/oocyte. To date, no available data show the impact of obesity on vitrification in mouse embryos. The aim of this study was to establish a murine model of maternal diet-induced obesity and to characterize the effect of obesity on vitrification by investigating the survival rate and embryo developmental competence after thawing. METHODS: Prospective comparisons were performed between six--eight-cell embryos from obese and normal-weight mice and between fresh and vitrified embryos. Female C57BL/6 mice were fed standard rodent chow (normal-weight group) or a high-fat diet (obese group) for 6 weeks. The mice were mated, zygotes were collected from oviducts and cultured for 3 days, and six--eight-cell embryos were then selected to assess lipid content in fresh embryos and to evaluate differences in apoptosis, survival, and development rates in response to vitrification. RESULTS: In fresh embryos from obese mice, the lipid content (0.044 vs 0.030, P<0.01) and apoptosis rate (15.1% vs.9.3%, P<0.05)were significantly higher, the survival rate (83.1% vs. 93.1%, P<0.01) on day 5 was significantly lower, and embryo development was notably delayed on days 3--5 compared with the normal-weight group. After vitrification, no significant difference was found between thawed embryos from obese and normal-weight mice in apoptosis, survival, and development rates on days 4 and 5. In both groups, pre- and post-vitrification embryo apoptosis, survival, and development rates were similar. CONCLUSIONS: This study demonstrated that differences in survival and developmental rates between embryos from obese and normal-weight mice were eliminated after vitrification. Thus, maternal obesity does not aggravate vitrification injury, but obesity alone greatly impairs pre-implantation embryo survival and development.     

Prolactin stress response does not predict brood desertion in a polyandrous shorebird

One of the fundamental principles of the life-history theory is that parents need to balance their resources between current and future offspring. Deserting the dependent young is a radical life-history decision that saves resources for future reproduction but that may cause the current brood to fail. Despite the importance of desertion for reproductive success, and thus fitness, the neuroendocrine mechanisms of brood desertion are largely unknown. We investigated two candidate hormones that may influence brood desertion in the Kentish plover Charadrius alexandrinus: prolactin ('parental hormone') and corticosterone ('stress hormone'). Kentish plovers exhibit an unusually diverse mating and parental care system: brood desertion occurs naturally since either parent (the male or the female) may desert the brood after the chicks hatch and mate with a new partner shortly after. We measured the hormone levels of parents at hatching using the standard capture and restraint protocol. We subsequently followed the broods to determine whether a parent deserted the chicks. We found no evidence that either baseline or stress-induced prolactin levels of male or female parents predicted brood desertion. Although stress-induced corticosterone levels were generally higher in females compared with males, individual corticosterone levels did not explain the probability of brood desertion. We suggest that, in this species, low prolactin levels do not trigger brood desertion. In general, we propose that the prolactin stress response does not reflect overall parental investment in a species where different parts of the breeding cycle are characterized by contrasting individual investment strategies.     

Translation during cold adaptation does not involve mRNA-rRNA base pairing through the downstream box

The downstream box (DB) has been proposed to enhance translation of several mRNAs and to be a key element controlling the expression of cold-shocked mRNAs. However, the proposal that the DB exerts its effects through a base pairing interaction with the complementary anti-downstream box (antiDB) sequence (nt 1469-1483) located in the penultimate stem (helix 44) of 16S rRNA remains controversial. The existence of this interaction during initiation of protein synthesis under cold-shock conditions has been investigated in the present work using an Escherichia coli strain whose ribosomes lack the potential to base pair with mRNA because of a 12 bp inversion of the antiDB sequence in helix 44. Our results show that this strain is capable of cold acclimation, withstands cold shock, and its ribosomes translate mRNAs that contain or lack DB sequences with similar efficiency, comparable to that of the wild type. The structure of helix 44 in 30S ribosomal subunits from cells grown at 37 degrees C and from cells subjected to cold shock was also analyzed by binding a 32P-labeled oligonucleotide complementary to the antiDB region and by chemical probing with DMS and kethoxal. Both approaches clearly indicate that this region is in a double-stranded conformation and therefore not available for base pairing with mRNA.     

Staphylococcus aureus DsbA does not have a destabilizing disulfide. A new paradigm for bacterial oxidative folding

In Gram-negative bacteria, the introduction of disulfide bonds into folding proteins occurs in the periplasm and is catalyzed by donation of an energetically unstable disulfide from DsbA, which is subsequently re-oxidized through interaction with DsbB. Gram-positive bacteria lack a classic periplasm but nonetheless encode Dsb-like proteins. Staphylococcus aureus encodes just one Dsb protein, a DsbA, and no DsbB. Here we report the crystal structure of S. aureus DsbA (SaDsbA), which incorporates a thioredoxin fold with an inserted helical domain, like its Escherichia coli counterpart EcDsbA, but it lacks the characteristic hydrophobic patch and has a truncated binding groove near the active site. These findings suggest that SaDsbA has a different substrate specificity than EcDsbA. Thermodynamic studies indicate that the oxidized and reduced forms of SaDsbA are energetically equivalent, in contrast to the energetically unstable disulfide form of EcDsbA. Further, the partial complementation of EcDsbA by SaDsbA is independent of EcDsbB and biochemical assays show that SaDsbA does not interact with EcDsbB. The identical stabilities of oxidized and reduced SaDsbA may facilitate direct re-oxidation of the protein by extracellular oxidants, without the need for DsbB.     

Frequency of radiation-induced micronuclei in neuronal cells does not correlate with clonogenic survival

It is generally assumed that radiation-induced micronuclei (MN) in cytokinesis-blocked cells are an expression of cellular radiosensitivity. Therefore, radiosensitive cells should have a high frequency of MN and radioresistant cells should show lower levels. We have irradiated cells of a panel of 13 neuronal cell lines of widely differing radiosensitivity [human neuroblastomas: N2alpha, SHSY5Y, SK-N-SH, KELLY and SK-N-BE(2c); murine neuroblastomas: OP-6 and OP-27; human glioblastomas: G120, G60, G28, G112, G44 and G62] and compared their radiation response using the micronucleus and standard clonogenic assays. It was found that micronucleus frequency was much higher in some of the radioresistant cell lines (N2alpha, G28, G120 and G44; SF2 >/= 0.60). These cell lines showed a high frequency of more than 0.32 MN per gray of (60)Co gamma radiation per binucleated cell. On the other hand, the more radiosensitive cell lines (OP-27 and SK-N-SH, SF2 相似文献   

Timing the start of division in E. coli: a single-cell study

We monitor the shape dynamics of individual E. coli cells using time-lapse microscopy together with accurate image analysis. This allows measuring the dynamics of single-cell parameters throughout the cell cycle. In previous work, we have used this approach to characterize the main features of single-cell morphogenesis between successive divisions. Here, we focus on the behavior of the parameters that are related to cell division and study their variation over a population of 30 cells. In particular, we show that the single-cell data for the constriction width dynamics collapse onto a unique curve following appropriate rescaling of the corresponding variables. This suggests the presence of an underlying time scale that determines the rate at which the cell cycle advances in each individual cell. For the case of cell length dynamics a similar rescaling of variables emphasizes the presence of a breakpoint in the growth rate at the time when division starts, tau(c). We also find that the tau(c) of individual cells is correlated with their generation time, tau(g), and inversely correlated with the corresponding length at birth, L(0). Moreover, the extent of the T-period, tau(g) - tau(c), is apparently independent of tau(g). The relations between tau(c), tau(g) and L(0) indicate possible compensation mechanisms that maintain cell length variability at about 10%. Similar behavior was observed for both fast-growing cells in a rich medium (LB) and for slower growth in a minimal medium (M9-glucose). To reveal the molecular mechanisms that lead to the observed organization of the cell cycle, we should further extend our approach to monitor the formation of the divisome.     

Gluconeogenic pathway does not display metabolic cold adaptation in liver of Antarctic notothenioid fish

Antarctic notothenioid fish display specializations related to cope with their chronically cold environment, such as high triacylglycerol (TAG) content in tissues. The metabolic fate of glycerol, a product of TAG mobilization, has not been studied in Antarctic fish. To assess the importance of glycerol as a substrate for gluconeogenesis and to determine whether this pathway is metabolically cold adapted (MCA), key hepatic enzyme activities were measured in Antarctic (Notothenia coriiceps, Gobionotothen gibberifrons, and Chionodraco rastrospinosus) and non-Antarctic (Dissostichus eleginoides, Patagonotothen ramsayi, and Eleginops maclovinus) notothenioid fish. Fructose 1,6-biphosphatase (FBP), phosphoenolpyruvate carboxykinase (PEPCK), and glycerol kinase (GK) activities were similar in both groups at common temperatures (1, 6, 11, or 21 °C). In particular, thermal sensitivity for the reactions catalyzed by FBP and PEPCK was analogous between Antarctic and non-Antarctic species, reflected by similar values for Arrhenius energy of activation (E _a) and Q₁₀. Additionally, hepatic glycerol, glucose, and glycogen contents together with plasma glycerol and glucose concentrations were similar for all of the species studied. Our results do not support the concept of MCA in hepatic gluconeogenesis and may indicate that the use of glycerol as a precursor for glucose synthesis by this pathway is of low physiological importance in Antarctic fish.