The importance of air quality for underground spaces: An international survey of public attitudes.

Space is a resource that is constantly being depleted, especially in mega-cities. Underground workspaces (UGS) are increasingly being included in urban plans and have emerged as an essential component of vertical cities. While progress had been made on the engineering aspects associated with the development of high-quality UGS, public attitudes toward UGS as work environments (ie, the public's design concerns with UGS) are relatively unknown. Here, we present the first large-scale study examining preferences and attitudes toward UGS, surveying close to 2000 participants from four cities in three continents (Singapore, Shanghai, London, and Montreal). Contrary to previous beliefs, air quality (and not lack of windows) is the major concern of prospective occupants. Windows, temperature, and lighting emerged as additional important building performance aspects for UGS. Early adopters (ie, individuals more willing to accept UGS and thus more likely to be the first occupants) across all cities prioritized air quality. Present results suggest that (perceived) air quality is a key building performance aspect for UGS that needs to be communicated to prospective occupants as this will improve their attitudes and views toward UGS. This study highlights the importance of indoor air quality for the public.

Long-term habituation of the C-start escape response in zebrafish larvae.

The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory.

Processing of Phonemic Consonant Length: Semantic and Fragment Priming Evidence from Bengali.

Six cross-modal lexical decision tasks with priming probed listeners' processing of the geminate-singleton contrast in Bengali, where duration alone leads to phonemic contrast ([pata] 'leaf' vs. [pat:a] 'whereabouts'), in order to investigate the phonological representation of consonantal duration in the lexicon. Four form-priming experiments (auditory fragment primes and visual targets) were designed to investigate listeners' sensitivity to segments of conflicting duration. Each prime derived from a real word ([k(h)[symbol: see text]m]/[g(h)en:]) was matched with a mispronunciation of the opposite duration (*[k(h)[symbol: see text]m:]/*[g(h)en]) and both were used to prime the full words [k(h)[symbol: see text]ma] ('forgiveness') and [g(h)en:a] ('disgust') respectively. Although all fragments led to priming, the results showed an asymmetric pattern. The fragments of words with singletons mispronounced as geminates led to equal priming, while those with geminates mispronounced as singletons showed a difference. The priming effect of the real-word geminate fragment was significantly greater than that of its corresponding nonword singleton fragment. In two subsequent semantic priming tasks with full-word primes a stronger asymmetry was found: nonword geminates (*[k(h)[symbol: see text]m:a]) primed semantically related words ([marjona] 'forgiveness') but singleton nonword primes (*[ghena]) did not show priming. This overall asymmetry in the tolerance of geminate nonwords in place of singleton words is attributed to a representational mismatch and points towards a moraic representation of duration. While geminates require a mora which cannot be derived from singleton input, the additional information in geminate nonwords does not create a similar mismatch.

Presynaptic NMDA receptor mechanisms for enhancing spontaneous neurotransmitter release.

NMDA receptors (NMDARs) are required for experience-driven plasticity during formative periods of brain development and are critical for neurotransmission throughout postnatal life. Most NMDAR functions have been ascribed to postsynaptic sites of action, but there is now an appreciation that presynaptic NMDARs (preNMDARs) can modulate neurotransmitter release in many brain regions, including the neocortex. Despite these advances, the cellular mechanisms by which preNMDARs can affect neurotransmitter release are largely unknown. Here we interrogated preNMDAR functions pharmacologically to determine how these receptors promote spontaneous neurotransmitter release in mouse primary visual cortex. Our results provide three new insights into the mechanisms by which preNMDARs can function. First, preNMDARs can enhance spontaneous neurotransmitter release tonically with minimal extracellular Ca(2+) or with major sources of intracellular Ca(2+) blocked. Second, lowering extracellular Na(+) levels reduces the contribution of preNMDARs to spontaneous transmitter release significantly. Third, preNMDAR enhance transmitter release in part through protein kinase C signaling. These data demonstrate that preNMDARs can act through novel pathways to promote neurotransmitter release in the absence of action potentials.

Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.

SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Small microdeletions and point mutations in SHANK3 have been identified in a small subgroup of individuals with autism spectrum disorder (ASD) and intellectual disability. SHANK3 also plays a key role in the chromosome 22q13.3 microdeletion syndrome (Phelan-McDermid syndrome), which includes ASD and cognitive dysfunction as major clinical features. To evaluate the role of Shank3 in vivo, we disrupted major isoforms of the gene in mice by deleting exons 4-9. Isoform-specific Shank3(e4-9) homozygous mutant mice display abnormal social behaviors, communication patterns, repetitive behaviors and learning and memory. Shank3(e4-9) male mice display more severe impairments than females in motor coordination. Shank3(e4-9) mice have reduced levels of Homer1b/c, GKAP and GluA1 at the PSD, and show attenuated activity-dependent redistribution of GluA1-containing AMPA receptors. Subtle morphological alterations in dendritic spines are also observed. Although synaptic transmission is normal in CA1 hippocampus, long-term potentiation is deficient in Shank3(e4-9) mice. We conclude that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations.

Bisphenol A Exposure Induces Sensory Processing Deficits in Larval Zebrafish during Neurodevelopment.

Because of their ex utero development, relatively simple nervous system, translucency, and availability of tools to investigate neural function, larval zebrafish are an exceptional model for understanding neurodevelopmental disorders and the consequences of environmental toxins. Furthermore, early in development, zebrafish larvae easily absorb chemicals from water, a significant advantage over methods required to expose developing organisms to chemical agents in utero Bisphenol A (BPA) and BPA analogs are ubiquitous environmental toxins with known molecular consequences. All humans have measurable quantities of BPA in their bodies. Most concerning, the level of BPA exposure is correlated with neurodevelopmental difficulties in people. Given the importance of understanding the health-related effects of this common toxin, we have exploited the experimental advantages of the larval zebrafish model system to investigate the behavioral and anatomic effects of BPA exposure. We discovered that BPA exposure early in development leads to deficits in the processing of sensory information, as indicated by BPA's effects on prepulse inhibition (PPI) and short-term habituation (STH) of the C-start reflex. We observed no changes in locomotion, thigmotaxis, and repetitive behaviors (circling). Despite changes in sensory processing, we detected no regional or whole-brain volume changes. Our results show that early BPA exposure can induce sensory processing deficits, as revealed by alterations in simple behaviors that are mediated by a well-defined neural circuit.

Induction of Short-Term Sensitization by an Aversive Chemical Stimulus in Zebrafish Larvae.

Larval zebrafish possess a number of molecular and genetic advantages for rigorous biological analyses of learning and memory. These advantages have motivated the search for novel forms of memory in these animals that can be exploited for understanding the cellular and molecular bases of vertebrate memory formation and consolidation. Here, we report a new form of behavioral sensitization in zebrafish larvae that is elicited by an aversive chemical stimulus [allyl isothiocyanate (AITC)] and that persists for ≥30 min. This form of sensitization is expressed as enhanced locomotion and thigmotaxis, as well as elevated heart rate. To characterize the neural basis of this nonassociative memory, we used transgenic zebrafish expressing the fluorescent calcium indicator GCaMP6 (Chen et al., 2013); because of the transparency of larval zebrafish, we could optically monitor neural activity in the brain of intact transgenic zebrafish before and after the induction of sensitization. We found a distinct brain area, previously linked to locomotion, that exhibited persistently enhanced neural activity following washout of AITC; this enhanced neural activity correlated with the behavioral sensitization. These results establish a novel form of memory in larval zebrafish and begin to unravel the neural basis of this memory.

Developmental regulation of the NMDA receptor subunits, NR3A and NR1, in human prefrontal cortex.

Subunit composition of N-methyl-D-aspartate-type glutamate receptors (NMDARs) dictates their function, yet the ontogenic profiles of human NMDAR subunits from gestation to adulthood have not been determined. We examined NMDAR mRNA and protein development in human dorsolateral prefrontal cortex (DLPFC), an area in which NMDARs are critical for higher cognitive processing and NMDAR hypofunction is hypothesized in schizophrenia. Using quantitative reverse transcriptase-polymerase chain reaction and western blotting, we found NR1 expression begins low prenatally, peaks in adolescence, yet remains high throughout life, suggesting lifelong importance of NMDAR function. In contrast, NR3A levels are low during gestation, surge soon after birth, and decline progressively through adolescence and into adulthood. Because NR3A subunits uniquely attenuate NMDAR-mediated currents, limit calcium influx, and suppress dendritic spine formation, high levels during early childhood may be important for regulating neuroprotection and activity-dependent sculpting of synapses. We also examined whether subunit changes underlie reduced NMDAR activity in schizophrenia. Our results reveal normal NR1 and NR3A protein levels in DLPFC from schizophrenic patients, indicating that NMDAR hypofunction is unlikely to be maintained by gross changes in NR3A-containing NMDARs or overall NMDAR numbers. These data provide insights into NMDAR functions in the developing CNS and will contribute to designing pharmacotherapies for neurological disorders.

Assessing the suitability of virtual reality for psychological testing.

Virtual reality (VR) is rapidly becoming an inexpensive, mainstream technology. VR technology is superambulatory as it allows participants to be examined under standardized environments and tests anywhere. In addition, it can test participants in different virtual spaces, including environments that are unsafe, inaccessible, costly or difficult to set up, or even nonexistent. We summarize the benefits and potential problems of VR technology, but we also move beyond theoretical approaches and present a customizable, open-source VR system (PSY-VR) that allows scalable psychological testing in modifiable VR environments. This system allows users to modify the environment using a simple graphical interface, without programming expertise. Moreover, as a proof-of-concept, we compare responses in a typical Flanker task between a real laboratory and a painstakingly matched virtual laboratory. Results indicate that the VR responses are comparable to real life testing, demonstrating the utility of VR for psychological assessment studies. The predicted rapid advancement of VR immersive technologies, as well the ease of their integration with physiological metrics ensures that VR-based assessment will be the modus operandi of psychological assessment in the future. This will allow controllable, low-cost assessment on a global scale. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Rapid habituation of a touch-induced escape response in Zebrafish (Danio rerio) Larvae.

Zebrafish larvae have several biological features that make them useful for cellular investigations of the mechanisms underlying learning and memory. Of particular interest in this regard is a rapid escape, or startle, reflex possessed by zebrafish larvae; this reflex, the C-start, is mediated by a relatively simple neuronal circuit and exhibits habituation, a non-associative form of learning. Here we demonstrate a rapid form of habituation of the C-start to touch that resembles the previously reported rapid habituation induced by auditory or vibrational stimuli. We also show that touch-induced habituation exhibits input specificity. This work sets the stage for in vivo optical investigations of the cellular sites of plasticity that mediate habituation of the C-start in the larval zebrafish.

Health Effects of Underground Workspaces cohort: study design and baseline characteristics.

The development of underground workspaces is a strategic effort towards healthy urban growth in cities with ever-increasing land scarcity. Despite the growth in underground workspaces, there is limited information regarding the impact of this environment on workers' health. The Health Effects of Underground Workspaces (HEUW) study is a cohort study that was set up to examine the health effects of working in underground workspaces. In this paper, we describe the rationale for the study, study design, data collection, and baseline characteristics of participants. The HEUW study recruited 464 participants at baseline, of whom 424 (91.4%) were followed-up at 3 months and 334 (72.0%) at 12 months from baseline. We used standardized and validated questionnaires to collect information on socio-demographic and lifestyle characteristics, medical history, family history of chronic diseases, sleep quality, health-related quality of life, chronotype, psychological distress, occupational factors, and comfort levels with indoor environmental quality parameters. Clinical and anthropometric parameters including blood pressure, spirometry, height, weight, and waist and hip circumference were also measured. Biochemical tests of participants' blood and urine samples were conducted to measure levels of glucose, lipids, and melatonin. We also conducted objective measurements of individuals' workplace environment, assessing air quality, light intensity, temperature, thermal comfort, and bacterial and fungal counts. The findings this study will help to identify modifiable lifestyle and environmental parameters that are negatively affecting workers' health. The findings may be used to guide the development of more health-promoting workspaces that attempt to negate any potential deleterious health effects from working in underground workspaces.

Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia.

Previously, we reported that long-term memory (LTM) in Aplysia can be reinstated by truncated (partial) training following its disruption by reconsolidation blockade and inhibition of PKM (Chen et al., 2014). Here, we report that LTM can be induced by partial training after disruption of original consolidation by protein synthesis inhibition (PSI) begun shortly after training. But when PSI occurs during training, partial training cannot subsequently establish LTM. Furthermore, we find that inhibition of DNA methyltransferase (DNMT), whether during training or shortly afterwards, blocks consolidation of LTM and prevents its subsequent induction by truncated training; moreover, later inhibition of DNMT eliminates consolidated LTM. Thus, the consolidation of LTM depends on two functionally distinct phases of protein synthesis: an early phase that appears to prime LTM; and a later phase whose successful completion is necessary for the normal expression of LTM. Both the consolidation and maintenance of LTM depend on DNA methylation.

A Psychosocial Approach to Understanding Underground Spaces.

With a growing need for usable land in urban areas, subterranean development has been gaining attention. While construction of large underground complexes is not a new concept, our understanding of various socio-cultural aspects of staying underground is still at a premature stage. With projected emergence of underground built environments, future populations may spend much more of their working, transit, and recreational time in underground spaces. Therefore, it is essential to understand the challenges and advantages that such environments have to improve the future welfare of users of underground spaces. The current paper discusses various psycho-social aspects of underground spaces, the impact they can have on the culture shared among the occupants, and possible solutions to overcome some of these challenges.

Synaptic facilitation and behavioral dishabituation in Aplysia: dependence on release of Ca2+ from postsynaptic intracellular stores, postsynaptic exocytosis, and modulation of postsynaptic AMPA receptor efficacy.

Sensitization and dishabituation of the defensive withdrawal reflex in Aplysia have been ascribed to presynaptic mechanisms, particularly presynaptic facilitation of transmission at sensorimotor synapses in the CNS of Aplysia. Here, we show that facilitation of sensorimotor synapses in cell culture during and after serotonin (5-HT) exposure depends on a rise in postsynaptic intracellular Ca(2+) and release of Ca(2+) from postsynaptic stores. We also provide support for the idea that postsynaptic AMPA receptor insertion mediates a component of synaptic facilitation by showing that facilitation after 5-HT offset is blocked by injecting botulinum toxin, an exocytotic inhibitor, into motor neurons before application of 5-HT. Using a reduced preparation, we extend our results to synaptic facilitation in the abdominal ganglion. We show that tail nerve shock-induced facilitation of siphon sensorimotor synapses also depends on elevated postsynaptic Ca(2+) and release of Ca(2+) from postsynaptic stores and recruits a late phase of facilitation that involves selective enhancement of the AMPA receptor-mediated synaptic response. To examine the potential role of postsynaptic exocytosis of AMPA receptors in learning in Aplysia, we test the effect of injecting botulinum toxin into siphon motor neurons on dishabituation of the siphon-withdrawal reflex. We find that postsynaptic injections of the toxin block dishabituation resulting from tail shock. Our results indicate that postsynaptic mechanisms, particularly Ca(2+)-dependent modulation of AMPA receptor trafficking, play a critical role in synaptic facilitation as well as in dishabituation and sensitization in Aplysia.

Learning in Aplysia: looking at synaptic plasticity from both sides.

Until recently, learning and memory in invertebrate organisms was believed to be mediated by relatively simple presynaptic mechanisms. By contrast, learning and memory in vertebrate organisms is generally thought to be mediated, at least in part, by postsynaptic mechanisms. But new experimental evidence from research using a model invertebrate organism, the marine snail Aplysia, indicates that this apparent distinction between invertebrate and vertebrate synaptic mechanisms of learning is invalid: learning in Aplysia cannot be explained in terms of exclusively presynaptic mechanisms. NMDA-receptor-dependent LTP appears to be necessary for classical conditioning in Aplysia. Furthermore, modulation of trafficking of postsynaptic ionotropic glutamate receptors underlies behavioral sensitization in this snail. Exclusively presynaptic processes appear to support only relatively brief memory in Aplysia. More persistent memory is likely to be mediated by postsynaptic processes, or by presynaptic processes whose expression depends upon retrograde signals.

Hematological and blood viscosity changes in tail-suspended rats.

BACKGROUND: Fluid shifts during exposure to microgravity result in a decrease in plasma volume which can lead to a transient increase in hematocrit. This transient increase in hematocrit could result in an increased blood viscosity. Yet, hematocrit returns to near normal values within a matter of hours of microgravity exposure as a result of a reduction in red blood cell mass. Rat tail-suspension models mimic the fluid shifts and hematological changes associated with microgravity exposure. METHODS: Tail-suspended rats were monitored for hematological and hemorheological changes over 4, 24, 72, and 168 h of tail suspension. Additionally, hematological and hemorheological changes were followed during recovery periods of 48, 120, and 192 h following 168 h of tail suspension. RESULTS: Although hematocrit increased significantly by 4 h of suspension, blood viscosity did not differ from controls. However, blood viscosity was significantly greater in the 72-, 168-, and 168/48-h suspension groups relative to controls despite no significant differences in hematocrits between groups. Theoretical calculations of blood viscosity at hematocrits of 50 and 60% (values intended to mimic hematocrits that would occur if red blood cell mass did not decrease) show a significant increase relative to the blood viscosities determined for the actual hematocrits in the experimental groups. CONCLUSIONS: The lowering of hematocrit associated with spaceflight may substantially reduce blood viscosity and thereby maintain the hematocrit at an optimal level for oxygen delivery to tissues.

Asymmetric processing of durational differences - electrophysiological investigations in Bengali.

Duration is used contrastively in many languages to distinguish word meaning (e.g. in Bengali, [pata] 'leaf' vs. [pat:a] 'whereabouts'). While there is a large body of research on other contrasts in speech perception (e.g. vowel contrasts and consonantal place features), little work has been done on how durational information is used in speech processing. In non-linguistic studies of low-level processing, such as visual and non-linguistic acoustic pop-out tasks, an asymmetry is found where additional information is more readily detected than missing information. In this study, event-related potentials were recorded during two cross-modal auditory-visual semantic priming studies, where nonword mispronunciations of spoken prime words were created by changing the duration of a medial consonant (real word [dana] 'seed'>nonword [dan:a]). N400 amplitudes showed an opposite asymmetric pattern of results, where increases in consonantal duration were tolerated and led to priming of the visual target, but decreases in consonantal duration were not accepted. This asymmetrical pattern of acceptability is attributed to the fact that a longer consonant includes all essential information for the recognition of the original word with a short medial consonant (a possible default category) and any additional information can be ignored. However, when a consonant is shortened, it lacks the required durational information to activate the word with the original long consonant.

Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.

Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories.

Learning and memory in zebrafish larvae.

Larval zebrafish possess several experimental advantages for investigating the molecular and neural bases of learning and memory. Despite this, neuroscientists have only recently begun to use these animals to study memory. However, in a relatively short period of time a number of forms of learning have been described in zebrafish larvae, and significant progress has been made toward their understanding. Here we provide a comprehensive review of this progress; we also describe several promising new experimental technologies currently being used in larval zebrafish that are likely to contribute major insights into the processes that underlie learning and memory.