Etiology of Sarcoidosis: Does Infection Play a Role?

Sarcoidosis is a granulomatous inflammatory disorder of unclear etiology, which is known to affect multiple organ systems including the lungs, heart, skin, central nervous system, and eyes, among others. For this reason, sarcoidosis represents a systemic medical disorder that is clinically relevant to multiple medical sub-specialties. Despite extensive research, the etiology of sarcoidosis has yet to be elucidated, although most evidence supports that the pathogenetic mechanism of sarcoidosis is an aberrant immune response, driven by an unidentified antigen (or antigens) in genetically susceptible individuals. Multiple candidate etiologic agents, including microbial organisms and environmental agents, have been investigated, but study results are inconclusive. In this review, we describe the known histologic and immunologic features of sarcoidosis and discuss the evidence supporting a role for infectious processes in the pathogenesis of sarcoidosis.     

Does Sleep Really Influence Face Recognition Memory?

Mounting evidence implicates sleep in the consolidation of various kinds of memories. We investigated the effect of sleep on memory for face identity, a declarative form of memory that is indispensable for nearly all social interaction. In the acquisition phase, observers viewed faces that they were required to remember over a variable retention period (0–36 hours). In the test phase, observers viewed intermixed old and new faces and judged seeing each before. Participants were classified according to acquisition and test times into seven groups. Memory strength (d′) and response bias (c) were evaluated. Substantial time spent awake (12 hours or more) during the retention period impaired face recognition memory evaluated at test, whereas sleep per se during the retention period did little to enhance the memory. Wakefulness during retention also led to a tightening of the decision criterion. Our findings suggest that sleep passively and transiently shelters face recognition memory from waking interference (exposure) but does not actively aid in its long-term consolidation.     

Does Auxin Play a Role in the Release of Apical Dominance by Shoot Inversion in Ipomoea nil?

According to the auxin-inhibition hypothesis of apical dominance,apically produced auxin moves down the stem and inhibits axillarybud outgrowth, either directly or indirectly. This hypothesishas been examined further by monitoring changes in basipetalauxin transport and endogenous auxin concentration in Ipomoeanil caused by shoot inversion, a stimulus that releases apicaldominance. The results indicate that inversion reduces auxintransport in the main stem. In upright shoots of intact plants,a 16-h pretreatment with [³H]IAA 4 cm below the apex resultsin downward movement of label and accumulation in nodes, especiallythe cotyledonary node. Label does not accumulate in the lateralbuds. GC-MS determinations of endogenous free auxin level inthe fourth node, where a lateral bud grows out following inversionof the upper part of the shoot, show no changes at 3 and 8 hafter inversion, the range of times for inversion-induced budrelease, or at 24 h, when bud outgrowth is continuing. However,inversion did cause a just-detectable decrease (approx. 10%)in the IAA level of the shoot's elongation region. Althoughauxin transport in segments of the main stem is partially inhibitedby inversion over a period shorter than the latent time of budrelease, thus providing a means for the expected depletion ofauxin in the fourth node, no depletion could be detected there.These results suggest that either a decrease in IAA level inthe main stem is not causal of bud release or that the decreasedIAA pool responsible for bud release is compartmented and cannotbe measured in whole-tissue extracts.Copyright 1993, 1999 AcademicPress Apical dominance, auxin content, auxin transport, axillary bud release, GC-MS, Ipomoea nil, Pharbitis nil, shoot inversion     

Does Recall after Sleep-Dependent Memory Consolidation Reinstate Sensitivity to Retroactive Interference?

Previous studies have shown that newly encoded memories are more resistant to retroactive interference when participants are allowed to sleep after learning the original material, suggesting a sleep-related strengthening of memories. In the present study, we investigated delayed, long-term effects of sleep vs. sleep deprivation (SD) on the first post-training night on memory consolidation and resistance to interference. On day 1, participants learned a list of unrelated word pairs (AB), either in the morning or in the evening, then spent the post-training night in a sleep or sleep deprivation condition, in a within-subject paradigm. On day 4, at the same time of day, they learned a novel list of word pairs (AC) in which 50% of the word pairs stemmed with the same word than in the AB list, resulting in retroactive interference. Participants had then to recall items from the AB list upon presentation of the “A” stem. Recall was marginally improved in the evening, as compared to the morning learning group. Most importantly, retroactive interference effects were found in the sleep evening group only, contrary to the hypothesis that sleep exerts a protective role against intrusion by novel but similar learning. We tentatively suggest that these results can be explained in the framework of the memory reconsolidation theory, stating that exposure to similar information sets back consolidated items in a labile form again sensitive to retroactive interference. In this context, sleep might not protect against interference but would promote an update of existing episodic memories while preventing saturation of the memory network due to the accumulation of dual traces.     

Does Phospholipid Methylation Play a Role in the Primary Mechanism of Action of Nerve Growth Factor?

Nerve growth factor (NGF)-untreated (naive) and neurite-bearing NGF-treated ("primed") PC12 rat pheochromocytoma cells were used as model system to study the role of phospholipid methylation in the NGF mechanism of action. The neurite-bearing cultures were deprived of NGF for 3 h before experimentation. Under both experimental conditions, the cells were labelled with [methyl-3H]methionine and then challenged with NGF for time periods ranging from 5 s to 30 min. Methylated phospholipids were extracted and then resolved and identified by TLC as phosphatidyl mono-, di-, and trimethyl ethanolamine. Quantification of the amount of radioactivity incorporated into each of the phospholipids indicated that NGF does not significantly alter phospholipid methylation either in naive or in neurite-bearing cells. Furthermore, using a methyltransferase inhibitor, it was found that neurite outgrowth still occurs when phospholipid methylation is almost completely blocked. These results indicate that phospholipid methylation does not play a primary role in the mechanism of action of NGF.     

Ganglion Cell Adaptability: Does the Coupling of Horizontal Cells Play a Role?

Background

The visual system can adjust itself to different visual environments. One of the most well known examples of this is the shift in spatial tuning that occurs in retinal ganglion cells with the change from night to day vision. This shift is thought to be produced by a change in the ganglion cell receptive field surround, mediated by a decrease in the coupling of horizontal cells.

Methodology/Principal Findings

To test this hypothesis, we used a transgenic mouse line, a connexin57-deficient line, in which horizontal cell coupling was abolished. Measurements, both at the ganglion cell level and the level of behavioral performance, showed no differences between wild-type retinas and retinas with decoupled horizontal cells from connexin57-deficient mice.

Conclusion/Significance

This analysis showed that the coupling and uncoupling of horizontal cells does not play a dominant role in spatial tuning and its adjustability to night and day light conditions. Instead, our data suggest that another mechanism, likely arising in the inner retina, must be responsible.     

Does Ethylene Play a Role in the Release of Lateral Buds (Tillers) from Apical Dominance in Oats?

The growth of lateral buds (tillers), which are undergoing release from apical dominance, was measured in upright and gravistimulated intact Avena sativa L. cv. `Victory' (oat) shoots as well as in isolated Avena stem segments treated with kinetin and sucrose. During release, the tiller bud initially shows a slow rate of elongation accompanied by swelling. It is followed by a more rapid rate of elongation. Ethylene (C₂H₄) production in shoot segments containing a tiller bud was found to occur at the onset of tiller swelling during gravistimulation as well as during inflorescence emergence. Exogenous application of indoleacetic acid or C₂H₄ inhibits kinetin-induced tiller bud swelling and elongation. However, stem segments pulsed for 24 hours in C₂H₄ or the C₂H₄ biosynthesis precursor, 1-amino-cyclopropane-1-carboxylic acid (ACC) and then transferred to kinetin and sucrose, showed a significant increase in swelling elongation as compared with segments maintained under the same conditions but without C₂H₄ or ACC in the pulse. Segments pulsed for 24 hours with kinetin and sucrose plus the ACC biosynthesis inhibitor, aminoethoxyvinylglycine, or the C₂H₄ action inhibitor, CO₂, then transferred to kinetin and sucrose medium, showed inhibition of tiller swelling during the pulse and of subsequent elongation. These results indicate that C₂H₄ plays a role in promoting tiller swelling during the onset of tiller release from apical dominance and may act as a modulator hormone in promoting tiller elongation in the presence of cytokinin.     

Female Gender and Differences in Outcome after Isolated Coronary Artery Bypass Graft Surgery: Does Age Play a Role?

Introduction

Female gender is a known risk factor for early and late mortality after coronary artery bypass graft surgery (CABG). Higher age of women at operation may influence outcome, since age per se is also an important risk factor. The purpose of our study was to analyze possible gender differences in outcome after isolated CABG in different age groups to delineate the impact of female gender and age.

Methods

All patients over 60 years of age undergoing isolated CABG at our department during 2001 and 2011 were included and categorized by age into sexagenarians (2266, 16.6% women), septuagenarians (2332, 25.4% women) and octogenarians (374, 32% women) and assessed by gender for 30-day and 180-day mortality.

Results

Thirty-day mortality was significantly higher in women only amongst septuagenarians (7.1 vs. 4.7%, p = 0.033). Same differences apply for 180-day mortality (12.3 vs. 8.2%, p = 0.033) and estimated one-year survival (81.6 ± 4.2 vs. 86.9 ± 2.2%, p = 0.001). Predictive factors for 30-day mortality of septuagenarian were logistic EuroSCORE (ES) (p = 0.003), perioperative myocardial infarction (MI) (p<0.001), pneumonia (p<0.001), abnormal LV-function (p<0.04) and use of LIMA graft (p<0.001), but not female gender. However, female gender was found to be an independent predictor for 180-day mortality (HR 1.632, p = 0.001) in addition to ES, use of LIMA graft, perioperative MI, pneumonia and abnormal LV function (HR 1.013, p = 0.004; HR 0.523, p<0.001; HR 2.710, p<0.001; HR 3.238, p<0.001; HR 2.013, p<0.001).

Conclusion

Women have a higher observed probability of early death after CABG in septuagenarians. However, female gender was not found to be an independent risk factor for 30-day, but for 180-day survival. Therefore, reduction of high impact risk factors such as perioperative MI and enhancement of LIMA use should be future goals. In view of our findings, decision for surgical revascularization should not be based on gender.     

Does Sleep Improve Your Grammar? Preferential Consolidation of Arbitrary Components of New Linguistic Knowledge

We examined the role of sleep-related memory consolidation processes in learning new form-meaning mappings. Specifically, we examined a Complementary Learning Systems account, which implies that sleep-related consolidation should be more beneficial for new hippocampally dependent arbitrary mappings (e.g. new vocabulary items) relative to new systematic mappings (e.g. grammatical regularities), which can be better encoded neocortically. The hypothesis was tested using a novel language with an artificial grammatical gender system. Stem-referent mappings implemented arbitrary aspects of the new language, and determiner/suffix+natural gender mappings implemented systematic aspects (e.g. tib scoiffesh + ballerina, tib mofeem + bride; ked jorool + cowboy, ked heefaff + priest). Importantly, the determiner-gender and the suffix-gender mappings varied in complexity and salience, thus providing a range of opportunities to detect beneficial effects of sleep for this type of mapping. Participants were trained on the new language using a word-picture matching task, and were tested after a 2-hour delay which included sleep or wakefulness. Participants in the sleep group outperformed participants in the wake group on tests assessing memory for the arbitrary aspects of the new mappings (individual vocabulary items), whereas we saw no evidence of a sleep benefit in any of the tests assessing memory for the systematic aspects of the new mappings: Participants in both groups extracted the salient determiner-natural gender mapping, but not the more complex suffix-natural gender mapping. The data support the predictions of the complementary systems account and highlight the importance of the arbitrariness/systematicity dimension in the consolidation process for declarative memories.