Femtosecond laser microdissection for isolation of regenerating C. elegans neurons for single-cell RNA sequencing.

Our understanding of nerve regeneration can be enhanced by delineating its underlying molecular activities at single-neuron resolution in model organisms such as Caenorhabditis elegans. Existing cell isolation techniques cannot isolate neurons with specific regeneration phenotypes from C. elegans. We present femtosecond laser microdissection (fs-LM), a single-cell isolation method that dissects specific cells directly from living tissue by leveraging the micrometer-scale precision of fs-laser ablation. We show that fs-LM facilitates sensitive and specific gene expression profiling by single-cell RNA sequencing (scRNA-seq), while mitigating the stress-related transcriptional artifacts induced by tissue dissociation. scRNA-seq of fs-LM isolated regenerating neurons revealed transcriptional programs that are correlated with either successful or failed regeneration in wild-type and dlk-1 (0) animals, respectively. This method also allowed studying heterogeneity displayed by the same type of neuron and found gene modules with expression patterns correlated with axon regrowth rate. Our results establish fs-LM as a spatially resolved single-cell isolation method for phenotype-to-genotype mapping.

Prosocial motives underlie scientific censorship by scientists: A perspective and research agenda.

Science is among humanity's greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions.

A smartphone intervention that enhances real-world memory and promotes differentiation of hippocampal activity in older adults.

The act of remembering an everyday experience influences how we interpret the world, how we think about the future, and how we perceive ourselves. It also enhances long-term retention of the recalled content, increasing the likelihood that it will be recalled again. Unfortunately, the ability to recollect event-specific details and reexperience the past tends to decline with age. This decline in recollection may reflect a corresponding decrease in the distinctiveness of hippocampal memory representations. Despite these well-established changes, there are few effective cognitive behavioral interventions that target real-world episodic memory. We addressed this gap by developing a smartphone-based application called HippoCamera that allows participants to record labeled videos of everyday events and subsequently replay, high-fidelity autobiographical memory cues. In two experiments, we found that older adults were able to easily integrate this noninvasive intervention into their daily lives. Using HippoCamera to repeatedly reactivate memories for real-world events improved episodic recollection and it evoked more positive autobiographical sentiment at the time of retrieval. In both experiments, these benefits were observed shortly after the intervention and again after a 3-mo delay. Moreover, more detailed recollection was associated with more differentiated memory signals in the hippocampus. Thus, using this smartphone application to systematically reactivate memories for recent real-world experiences can help to maintain a bridge between the present and past in older adults.

Toward a coordinated understanding of hydro-biogeochemical root functions in tropical forests for application in vegetation models.

Tropical forest root characteristics and resource acquisition strategies are underrepresented in vegetation and global models, hampering the prediction of forest-climate feedbacks for these carbon-rich ecosystems. Lowland tropical forests often have globally unique combinations of high taxonomic and functional biodiversity, rainfall seasonality, and strongly weathered infertile soils, giving rise to distinct patterns in root traits and functions compared with higher latitude ecosystems. We provide a roadmap for integrating recent advances in our understanding of tropical forest belowground function into vegetation models, focusing on water and nutrient acquisition. We offer comparisons of recent advances in empirical and model understanding of root characteristics that represent important functional processes in tropical forests. We focus on: (1) fine-root strategies for soil resource exploration, (2) coupling and trade-offs in fine-root water vs nutrient acquisition, and (3) aboveground-belowground linkages in plant resource acquisition and use. We suggest avenues for representing these extremely diverse plant communities in computationally manageable and ecologically meaningful groups in models for linked aboveground-belowground hydro-nutrient functions. Tropical forests are undergoing warming, shifting rainfall regimes, and exacerbation of soil nutrient scarcity caused by elevated atmospheric CO2. The accurate model representation of tropical forest functions is crucial for understanding the interactions of this biome with the climate.

Las características de las raíces de los bosques tropicales y las estrategias de adquisición de recursos están subrepresentadas en modelos de vegetación, lo que dificulta la predicción del efecto de cambio de clima para estos ecosistemas ricos en carbono. Los bosques tropicales a menudo tienen combinaciones únicas a nivel mundial de alta biodiversidad taxonómica y funcional, estacionalidad de precipitación, y suelos infértiles, dando lugar a patrones distintos en los rasgos y funciones de las raíces en comparación con los ecosistemas de latitudes más altas. Integramos los avances recientes en nuestra comprensión de la función subterránea de los bosques tropicales en modelos de vegetación, centrándonos en la adquisición de agua y nutrientes. Ofrecemos comparaciones de avances recientes en la comprensión empírica y de modelos de las características de las raíces que representan procesos funcionales importantes en los bosques tropicales. Nos centramos en: (1) estrategias de raíces finas para adquisición de recursos del suelo, (2) acoplamiento y compensaciones entre adquisición del agua y de nutrientes, y (3) vínculos entre funciones sobre tierra y debajo del superficie en bosques tropicales. Sugerimos vías para representar estas comunidades de plantas extremadamente diversas en grupos computacionalmente manejables y ecológicamente significativos en modelos. Los bosques tropicales se están calentando, tienen cambios en los regímenes de lluvias, y tienen una exacerbación de la escasez de nutrientes del suelo causada por el elevado CO2 atmosférico. La representación precisa de las funciones de los bosques tropicales en modelos es crucial para comprender las interacciones de este bioma con el clima.

Spatial context scaffolds long-term episodic richness of weaker real-world autobiographical memories in both older and younger adults.

Remembering life experiences involves recalling not only what occurred (episodic details), but also where an event took place (spatial context), both of which decline with age. Although spatial context can cue episodic detail recollection, it is unknown whether initially recalling an event alongside greater reinstatement of spatial context protects memory for episodic details in the long term, and whether this is affected by age. Here, we analysed 1079 personally-experienced, real-world events from 29 older adults and 12 younger adults. Events were recalled first on average 6 weeks after they occurred and then again on average 24 weeks after they occurred. We developed a novel scoring protocol to quantify spatial contextual details and used the established Autobiographical Interview to quantify episodic details. We found improved recall of episodic details after a delay if those details had initially been recalled situated in greater spatial context. Notably, for both older and younger adults, this preservation was observed for memories initially recalled with low, but not high, numbers of episodic details, suggesting that spatial context aided episodic retrieval for memories that required more support. This work supports the notion that spatial context scaffolds detail-rich event recollection and inspires memory interventions that leverage this spatial scaffold.

Resolving Cross-modal Semantic Interference among Object Concepts Requires Medial Temporal Lobe Cortex.

The ability to flexibly categorize object concepts is essential to semantic cognition because the features that make two objects similar in one context may be irrelevant and even constitute interference in another. Thus, adaptive behavior in complex and dynamic environments requires the resolution of feature-based interference. In the current case study, we placed visual and functional semantic features in opposition across object concepts in two categorization tasks. Successful performance required the resolution of functional interference in a visual categorization task and the resolution of visual interference in a functional categorization task. In Experiment 1, we found that patient D. A., an individual with bilateral temporal lobe lesions, was unable to categorize object concepts in a context-dependent manner. His impairment was characterized by an increased tendency to incorrectly group objects that were similar on the task-irrelevant dimension, revealing an inability to resolve cross-modal semantic interference. In Experiment 2, D. A.'s categorization accuracy was comparable to controls when lures were removed, indicating that his impairment is unique to contexts that involve cross-modal interference. In Experiment 3, he again performed as well as controls when categorizing simple concepts, suggesting that his impairment is specific to categorization of complex object concepts. These results advance our understanding of the anterior temporal lobe as a system that represents object concepts in a manner that enables flexible semantic cognition. Specifically, they reveal a dissociation between semantic representations that contribute to the resolution of cross-modal interference and those that contribute to the resolution of interference within a given modality.

Hydraulic variability of tropical forests is largely independent of water availability.

Tropical rainforest woody plants have been thought to have uniformly low resistance to hydraulic failure and to function near the edge of their hydraulic safety margin (HSM), making these ecosystems vulnerable to drought; however, this may not be the case. Using data collected at 30 tropical forest sites for three key traits associated with drought tolerance, we show that site-level hydraulic diversity of leaf turgor loss point, resistance to embolism (P50 ), and HSMs is high across tropical forests and largely independent of water availability. Species with high HSMs (>1 MPa) and low P50 values (< -2 MPa) are common across the wet and dry tropics. This high site-level hydraulic diversity, largely decoupled from water stress, could influence which species are favoured and become dominant under a drying climate. High hydraulic diversity could also make these ecosystems more resilient to variable rainfall regimes.

No gesture too small: An investigation into the ability of gestural information to mislead eyewitness accounts by 5- to 8-year-olds.

The accuracy of eyewitness interviews has legal and clinical implications within the criminal justice system. Leading verbal suggestions have been shown to give rise to false memories and inaccurate testimonies in children, but only a small body of research exists regarding non-verbal communication. The present study examined whether 5- to 8-year-olds in the UK could be misled about their memory of an event through exposure to leading gestural information, which suggested an incorrect response, using a variety of question and gesture types. Results showed that leading gestures significantly corrupted participants' memory compared to the control group (MD = 0.60, p < 0.001), with participants being misled by at least one question nearly three-quarters of the time. Questions about peripheral details, and gestures that were more visible and expressive, increased false memory further, with even subtle gestures demonstrating a strong misleading influence. We discuss the implications of these findings for the guidelines governing eyewitness interviews.

Involuntary memory signals in the medial temporal lobe.

We highlight recent progress in neuroimaging and neuropsychological research on memory mechanisms in the medial temporal lobe that speaks to the involuntary nature of memory retrieval processes. We suggest that evidence form these studies supports Barzykowski and Moulin's proposal that memory signals involved in experiences of familiarity and déjà vu can be generated in the absence of retrieval intentionality.

Leaf habit affects the distribution of drought sensitivity but not water transport efficiency in the tropics.

Considering the global intensification of aridity in tropical biomes due to climate change, we need to understand what shapes the distribution of drought sensitivity in tropical plants. We conducted a pantropical data synthesis representing 1117 species to test whether xylem-specific hydraulic conductivity (KS ), water potential at leaf turgor loss (ΨTLP ) and water potential at 50% loss of KS (ΨP50 ) varied along climate gradients. The ΨTLP and ΨP50 increased with climatic moisture only for evergreen species, but KS did not. Species with high ΨTLP and ΨP50 values were associated with both dry and wet environments. However, drought-deciduous species showed high ΨTLP and ΨP50 values regardless of water availability, whereas evergreen species only in wet environments. All three traits showed a weak phylogenetic signal and a short half-life. These results suggest strong environmental controls on trait variance, which in turn is modulated by leaf habit along climatic moisture gradients in the tropics.

Hurricanes increase tropical forest vulnerability to drought.

Rapid changes in climate and disturbance regimes, including droughts and hurricanes, are likely to influence tropical forests, but our understanding of the compound effects of disturbances on forest ecosystems is extremely limited. Filling this knowledge gap is necessary to elucidate the future of these ecosystems under a changing climate. We examined the relationship between hurricane response (damage, mortality, and resilience) and four hydraulic traits of 13 dominant woody species in a wet tropical forest subject to periodic hurricanes. Species with high resistance to embolisms (low P50 values) and higher safety margins ( SMP50 ) were more resistant to immediate hurricane mortality and breakage, whereas species with higher hurricane resilience (rapid post-hurricane growth) had high capacitance and P50 values and low SMP50 . During 26 yr of post-hurricane recovery, we found a decrease in community-weighted mean values for traits associated with greater drought resistance (leaf turgor loss point, P50 , SMP50 ) and an increase in capacitance, which has been linked with lower drought resistance. Hurricane damage favors slow-growing, drought-tolerant species, whereas post-hurricane high resource conditions favor acquisitive, fast-growing but drought-vulnerable species, increasing forest productivity at the expense of drought tolerance and leading to higher overall forest vulnerability to drought.

Relationship between déjà vu experiences and recognition-memory impairments in temporal-lobe epilepsy.

Déjà vu is characterised by feelings of familiarity and concurrent awareness that this familiarity is wrong. Previous neuropsychological research has linked déjà vu during seizures in individuals with unilateral temporal-lobe epilepsy (uTLE) to rhinal-cortex abnormalities, and to recognition-memory deficits that selectively affect familiarity assessment. Here, we examined whether bilateral TLE patients with déjà vu (bTLE) show a similar pattern of performance. Using two experimental tasks, we found that bTLE patients exhibit deficits not only for familiarity but also for recollection. Relative to uTLE, this broader impairment also involved hippocampal abnormalities. Our findings confirm rhinal-cortex contributions to the generation of false familiarity in déjà vu that parallel its contributions to familiarity on recognition-memory tasks. While they do not rule out a role for recollection in identifying this familiarity as wrong, the deficits observed in bTLE patients weigh against the notion that any such role is necessary for déjà vu to occur.

Allometric scaling laws linking biomass and rooting depth vary across ontogeny and functional groups in tropical dry forest lianas and trees.

There are two theories about how allocation of metabolic products occurs. The allometric biomass partitioning theory (APT) suggests that all plants follow common allometric scaling rules. The optimal partitioning theory (OPT) predicts that plants allocate more biomass to the organ capturing the most limiting resource. Whole-plant harvests of mature and juvenile tropical deciduous trees, evergreen trees, and lianas and model simulations were used to address the following knowledge gaps: (1) Do mature lianas comply with the APT scaling laws or do they invest less biomass in stems compared to trees? (2) Do juveniles follow the same allocation patterns as mature individuals? (3) Is either leaf phenology or life form a predictor of rooting depth? It was found that: (1) mature lianas followed the same allometric scaling laws as trees; (2) juveniles and mature individuals do not follow the same allocation patterns; and (3) mature lianas had shallowest coarse roots and evergreen trees had the deepest. It was demonstrated that: (1) mature lianas invested proportionally similar biomass to stems as trees and not less, as expected; (2) lianas were not deeper-rooted than trees as had been previously proposed; and (3) evergreen trees had the deepest roots, which is necessary to maintain canopy during simulated dry seasons.

A catastrophic tropical drought kills hydraulically vulnerable tree species.

Drought-related tree mortality is now a widespread phenomenon predicted to increase in magnitude with climate change. However, the patterns of which species and trees are most vulnerable to drought, and the underlying mechanisms have remained elusive, in part due to the lack of relevant data and difficulty of predicting the location of catastrophic drought years in advance. We used long-term demographic records and extensive databases of functional traits and distribution patterns to understand the responses of 20-53 species to an extreme drought in a seasonally dry tropical forest in Costa Rica, which occurred during the 2015 El Niño Southern Oscillation event. Overall, species-specific mortality rates during the drought ranged from 0% to 34%, and varied little as a function of tree size. By contrast, hydraulic safety margins correlated well with probability of mortality among species, while morphological or leaf economics spectrum traits did not. This firmly suggests hydraulic traits as targets for future research.

Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy.

Optogenetic strategies to restore vision in patients who are blind from end-stage retinal degenerations aim to render remaining retinal cells light sensitive once photoreceptors are lost. Here, we assessed long-term functional outcomes following subretinal delivery of the human melanopsin gene (OPN4) in the rd1 mouse model of retinal degeneration using an adeno-associated viral vector. Ectopic expression of OPN4 using a ubiquitous promoter resulted in cellular depolarization and ganglion cell action potential firing. Restoration of the pupil light reflex, behavioral light avoidance, and the ability to perform a task requiring basic image recognition were restored up to 13 mo following injection. These data suggest that melanopsin gene therapy via a subretinal route may be a viable and stable therapeutic option for the treatment of end-stage retinal degeneration in humans.

Follow-up observation of patients with obstructive sleep apnea treated by maxillomandibular advancement.

INTRODUCTION: This study aimed to evaluate the follow-up observation of patients with obstructive sleep apnea treated with maxillomandibular advancement (MMA) procedure with or without genial tubercle advancement (GTA). METHODS: A total of 25 patients (mean age 37.1 ± 17.3 years) were included in the study. Cone-beam computed tomography scans were taken before treatment; after presurgical orthodontic treatment; immediately after MMA procedure; and follow-up visit. All Digital Imaging and Communications in Medicine files were analyzed using the Dolphin 3D Imaging software program (Dolphin Imaging and Management Solutions, Chatsworth, Calif) to determine the total airway volume (TAV), airway area (AA), and minimal cross-sectional area (MCA). Dolphin 3D voxel-based superimposition was used to determine the amount of skeletal advancement with MMA and changes after surgery. RESULTS: Significant increase in TAV, AA, and MCA was found with MMA treatment (40.6%, 28.8%, and 56.4%, respectively, P <0.0001). Smaller but significant decrease in TAV, AA, and MCA was found during a follow-up visit (20.0%, 9.7%, and 26.8%, respectively, P <0.0001) giving a net increase of TAV, AA and MCA (35.8%, 27.1%, and 45.9%, respectively). No significant differences were found in any of the airway measurements with or without the GTA procedure. The average forward movements of the maxilla, mandible, and chin were 6.6 mm, 8.2 mm, and 11.4 mm, respectively. A relapse of less than 1 mm was found in each of the variables during the follow-up period. No correlation was found between the magnitudes of skeletal advancement and the change in oropharyngeal airway space (OPAS). CONCLUSIONS: Significant increase in OPAS can be expected with MMA surgery with or without GTA procedure in patients diagnosed with obstructive sleep apnea. A partial loss in OPAS was found during the follow-up visit. The surgical movements were found to be stable, with less than 1 mm of relapse during the follow-up period, which was not clinically significant.

High Socioeconomic Status Predicts Substance Use and Alcohol Consumption in U.S. Undergraduates.

BACKGROUND: In health sociology, the prevailing consensus is that socioeconomic status (SES) lowers illness risk. This model neglects the fact that unhealthful consumption patterns may covary with affluence. The current study examines consumption of drugs and alcohol among affluent U.S. college students. OBJECTIVES: The article tests the hypothesis that undergraduate students from high-SES households have higher rates and levels of drug and alcohol consumption than their peers. METHODS: The study used self-report data from 18,611 18- to 24-year-old undergraduates across 23 public and private U.S. institutions from the Healthy Minds 2016 dataset. RESULTS: I found that high-SES undergraduates were more likely than peers to use marijuana, choose varied drugs, consume alcohol frequently, and use alcohol and substances to cope with stress. The first three results were robust after controlling for gender, race, residence type, and relationship status. Marital status and race were stronger predictors than SES. Asians and married students were the least likely to use alcohol and drugs. Conclusions/Importance: Findings supported the main hypotheses, and the effects were robust to controls. Consumption of illicit drugs and alcohol may be one hitherto neglected reason for downward mobility among economically privileged college students.

A Critical Role for Astrocytes in Hypercapnic Vasodilation in Brain.

Cerebral blood flow (CBF) is controlled by arterial blood pressure, arterial CO2, arterial O2, and brain activity and is largely constant in the awake state. Although small changes in arterial CO2 are particularly potent to change CBF (1 mmHg variation in arterial CO2 changes CBF by 3%-4%), the coupling mechanism is incompletely understood. We tested the hypothesis that astrocytic prostaglandin E2 (PgE2) plays a key role for cerebrovascular CO2 reactivity, and that preserved synthesis of glutathione is essential for the full development of this response. We combined two-photon imaging microscopy in brain slices with in vivo work in rats and C57BL/6J mice to examine the hemodynamic responses to CO2 and somatosensory stimulation before and after inhibition of astrocytic glutathione and PgE2 synthesis. We demonstrate that hypercapnia (increased CO2) evokes an increase in astrocyte [Ca2+]i and stimulates COX-1 activity. The enzyme downstream of COX-1 that synthesizes PgE2 (microsomal prostaglandin E synthase-1) depends critically for its vasodilator activity on the level of glutathione in the brain. We show that, when glutathione levels are reduced, astrocyte calcium-evoked release of PgE2 is decreased and vasodilation triggered by increased astrocyte [Ca2+]iin vitro and by hypercapnia in vivo is inhibited. Astrocyte synthetic pathways, dependent on glutathione, are involved in cerebrovascular reactivity to CO2 Reductions in glutathione levels in aging, stroke, or schizophrenia could lead to dysfunctional regulation of CBF and subsequent neuronal damage.SIGNIFICANCE STATEMENT Neuronal activity leads to the generation of CO2, which has previously been shown to evoke cerebral blood flow (CBF) increases via the release of the vasodilator PgE2 We demonstrate that hypercapnia (increased CO2) evokes increases in astrocyte calcium signaling, which in turn stimulates COX-1 activity and generates downstream PgE2 production. We demonstrate that astrocyte calcium-evoked production of the vasodilator PgE2 is critically dependent on brain levels of the antioxidant glutathione. These data suggest a novel role for astrocytes in the regulation of CO2-evoked CBF responses. Furthermore, these results suggest that depleted glutathione levels, which occur in aging and stroke, will give rise to dysfunctional CBF regulation and may result in subsequent neuronal damage.