Burning questions for a warming and changing world: 15 unknowns in plant abiotic stress.

We present unresolved questions in plant abiotic stress biology as posed by 15 research groups with expertise spanning eco-physiology to cell and molecular biology. Common themes of these questions include the need to better understand how plants detect water availability, temperature, salinity, and rising carbon dioxide (CO2) levels; how environmental signals interface with endogenous signaling and development (e.g. circadian clock and flowering time); and how this integrated signaling controls downstream responses (e.g. stomatal regulation, proline metabolism, and growth versus defense balance). The plasma membrane comes up frequently as a site of key signaling and transport events (e.g. mechanosensing and lipid-derived signaling, aquaporins). Adaptation to water extremes and rising CO2 affects hydraulic architecture and transpiration, as well as root and shoot growth and morphology, in ways not fully understood. Environmental adaptation involves tradeoffs that limit ecological distribution and crop resilience in the face of changing and increasingly unpredictable environments. Exploration of plant diversity within and among species can help us know which of these tradeoffs represent fundamental limits and which ones can be circumvented by bringing new trait combinations together. Better defining what constitutes beneficial stress resistance in different contexts and making connections between genes and phenotypes, and between laboratory and field observations, are overarching challenges.

Root plasticity under abiotic stress.

Abiotic stresses increasingly threaten existing ecological and agricultural systems across the globe. Plant roots perceive these stresses in the soil and adapt their architecture accordingly. This review provides insights into recent discoveries showing the importance of root system architecture (RSA) and plasticity for the survival and development of plants under heat, cold, drought, salt, and flooding stress. In addition, we review the molecular regulation and hormonal pathways involved in controlling RSA plasticity, main root growth, branching and lateral root growth, root hair development, and formation of adventitious roots. Several stresses affect root anatomy by causing aerenchyma formation, lignin and suberin deposition, and Casparian strip modulation. Roots can also actively grow toward favorable soil conditions and avoid environments detrimental to their development. Recent advances in understanding the cellular mechanisms behind these different root tropisms are discussed. Understanding root plasticity will be instrumental for the development of crops that are resilient in the face of abiotic stress.

Partial Least Squares Analysis of Alzheimer's Disease Biomarkers, Modifiable Health Variables, and Cognition in Older Adults with Mild Cognitive Impairment.

OBJECTIVES: To identify novel associations between modifiable physical and health variables, Alzheimer's disease (AD) biomarkers, and cognitive function in a cohort of older adults with Mild Cognitive Impairment (MCI). METHODS: Metrics of cardiometabolic risk, stress, inflammation, neurotrophic/growth factors, AD, and cognition were assessed in 154 MCI participants (Mean age = 74.1 years) from the Alzheimer's Disease Neuroimaging Initiative. Partial Least Squares analysis was employed to examine associations among these physiological variables and cognition. RESULTS: Latent variable 1 revealed a unique combination of AD biomarkers, neurotrophic/growth factors, education, and stress that were significantly associated with specific domains of cognitive function, including episodic memory, executive function, processing speed, and language, representing 45.2% of the cross-block covariance in the data. Age, body mass index, and metrics tapping basic attention or premorbid IQ were not significant. CONCLUSIONS: Our data-driven analysis highlights the significant relationships between metrics associated with AD pathology, neuroprotection, and neuroplasticity, primarily with tasks tapping episodic memory, executive function, processing speed, and verbal fluency rather than more basic tasks that do not require mental manipulation (basic attention and vocabulary). These data also indicate that biological metrics are more strongly associated with episodic memory, executive function, and processing speed than chronological age in older adults with MCI.

Hot topic: Thermosensing in plants.

Plants alter their morphology and cellular homeostasis to promote resilience under a variety of heat regimes. Molecular processes that underlie these responses have been intensively studied and found to encompass diverse mechanisms operating across a broad range of cellular components, timescales and temperatures. This review explores recent progress throughout this landscape with a particular focus on thermosensing in the model plant Arabidopsis. Direct temperature sensors include the photosensors phytochrome B and phototropin, the clock component ELF3 and an RNA switch. In addition, there are heat-regulated processes mediated by ion channels, lipids and lipid-modifying enzymes, taking place at the plasma membrane and the chloroplast. In some cases, the mechanism of temperature perception is well understood but in others, this remains an open question. Potential novel thermosensing mechanisms are based on lipid and liquid-liquid phase separation. Finally, future research directions of high temperature perception and signalling pathways are discussed.

On the evolution of plant thermomorphogenesis.

Plants have a remarkable capacity to acclimate to their environment. Acclimation is enabled to a large degree by phenotypic plasticity, the extent of which confers a selective advantage, especially in natural habitats. Certain key events in evolution triggered adaptive bursts necessary to cope with drastic environmental changes. One such event was the colonization of land 400-500 mya. Compared to most aquatic habitats, fluctuations in abiotic parameters became more pronounced, generating significant selection pressure. To endure these harsh conditions, plants needed to adapt their physiology and morphology and to increase the range of phenotypic plasticity. In addition to drought stress and high light, high temperatures and fluctuation thereof were among the biggest challenges faced by terrestrial plants. Thermomorphogenesis research has emerged as a new sub-discipline of the plant sciences and aims to understand how plants acclimate to elevated ambient temperatures through changes in architecture. While we have begun to understand how angiosperms sense and respond to elevated ambient temperature, very little is known about thermomorphogenesis in plant lineages with less complex body plans. It is unclear when thermomorphogenesis initially evolved and how this depended on morphological complexity. In this review, we take an evolutionary-physiological perspective and generate hypotheses about the emergence of thermomorphogenesis.

Far-Red Light Detection in the Shoot Regulates Lateral Root Development through the HY5 Transcription Factor.

Plants in dense vegetation compete for resources and detect competitors through reflection of far-red (FR) light from surrounding plants. This reflection causes a reduced red (R):FR ratio, which is sensed through phytochromes. Low R:FR induces shade avoidance responses of the shoot and also changes the root system architecture, although this has received little attention so far. Here, we investigate the molecular mechanisms through which light detection in the shoot regulates root development in Arabidopsis thaliana We do so using a combination of microscopy, gene expression, and mutant study approaches in a setup that allows root imaging without exposing the roots to light treatment. We show that low R:FR perception in the shoot decreases the lateral root (LR) density by inhibiting LR emergence. This decrease in LR emergence upon shoot FR enrichment is regulated by phytochrome-dependent accumulation of the transcription factor ELONGATED HYPOCOTYL5 (HY5) in the LR primordia. HY5 regulates LR emergence by decreasing the plasma membrane abundance of PIN-FORMED3 and LIKE-AUX1 3 auxin transporters. Accordingly, FR enrichment reduces the auxin signal in the overlaying cortex cells, and this reduces LR outgrowth. This shoot-to-root communication can help plants coordinate resource partitioning under competition for light in high density fields.

Acute Effects of High-intensity Resistance Exercise on Cognitive Function.

The purpose of the present study was to examine the influence of an acute bout of high-intensity resistance exercise on measures of cognitive function. Ten men (Mean ± SD: age = 24.4 ± 3.2 yrs; body mass = 85.7 ± 11.8 kg; height = 1.78 ± 0.08 m; 1 repetition maximum (1RM) = 139.0 ± 24.1 kg) gave informed consent and performed a high-intensity 6 sets of 10 repetitions of barbell back squat exercise at 80% 1RM with 2 minutes rest between sets. The Automated Neuropsychological Assessment Metrics (ANAM) was completed to assess various cognitive domains during the familiarization period, immediately before, and immediately after the high-intensity resistance exercise bout. The repeated measures ANOVAs for throughput scores (r·m-1) demonstrated significant mean differences for the Mathematical Processing task (MTH; p < 0.001, η2p = 0.625) where post hoc pairwise comparisons demonstrated that the post-fatigue throughput (32.0 ± 8.8 r·m-1) was significantly greater than the pre-fatigue (23.8 ± 7.4 r·m-1, p = 0.003, d = 1.01) and the familiarization throughput (26.4 ± 5.3 r·m-1, p = 0.024, d = 0.77). The Coded Substitution-Delay task also demonstrated significant mean differences (CDD; p = 0.027, η2p = 0.394) with post hoc pairwise comparisons demonstrating that the post-fatigue throughput (49.3 ± 14.4 r·m-1) was significantly less than the pre-fatigue throughput (63.2 ± 9.6 r·m-1, p = 0.011, d = 1.14). The repeated measures ANOVAs for reaction time (ms) demonstrated significant mean differences for MTH (p < 0.001, η2p = 0.624) where post hoc pairwise comparisons demonstrated that the post-fatigue reaction time (1885.2 ± 582.8 ms) was significantly less than the pre-fatigue (2518.2 ± 884.8 ms, p = 0.005, d = 0.85) and familiarization (2253.7 ± 567.6 ms, p = 0.009, d = 0.64) reaction times. The Go/No-Go task demonstrated significant mean differences (GNG; p = 0.031, η2p = 0.320) with post hoc pairwise comparisons demonstrating that the post-fatigue (285.9 ± 16.3 ms) was significantly less than the pre-fatigue (298.5 ± 12.1 ms, p = 0.006, d = 0.88) reaction times. High-intensity resistance exercise may elicit domain-specific influences on cognitive function, characterized by the facilitation of simple cognitive tasks and impairments of complex cognitive tasks.

The bHLH network underlying plant shade-avoidance.

Shade is a potential threat to many plant species. When shade-intolerant plants detect neighbours, they elongate their stems and leaves in an effort to maximise their light capture. This developmental programme, known as 'shade-avoidance' is tightly controlled by specialised photoreceptors and a suite of transcriptional regulators. The basic helix-loop-helix (bHLH) family of transcription factors are particularly important for shade-induced elongation. In recent years, it has become apparent that many members of this family heterodimerise and that together they form a complex regulatory network. This review summarises recent work into the structure of the bHLH network and how it regulates elongation growth. In addition to this, we highlight how photoreceptors modulate the function of the network via direct interaction with transcription factors. It is hoped that the information integrated in this review will provide a useful theoretical framework for future studies on the molecular basis of shade-avoidance in plants.

Hippocampal contributions to value-based learning: Converging evidence from fMRI and amnesia.

Recent evidence suggests that the human hippocampus-known primarily for its involvement in episodic memory-plays a role in a host of motivationally relevant behaviors, including some forms of value-based decision-making. However, less is known about the role of the hippocampus in value-based learning. Such learning is typically associated with a striatal system, yet a small number of studies, both in human and nonhuman species, suggest hippocampal engagement. It is not clear, however, whether this engagement is necessary for such learning. In the present study, we used both functional MRI (fMRI) and lesion-based neuropsychological methods to clarify hippocampal contributions to value-based learning. In Experiment 1, healthy participants were scanned while learning value-based contingencies (whether players in a "game" win money) in the context of a probabilistic learning task. Here, we observed recruitment of the hippocampus, in addition to the expected ventral striatal (nucleus accumbens) activation that typically accompanies such learning. In Experiment 2, we administered this task to amnesic patients with medial temporal lobe damage and to healthy controls. Amnesic patients, including those with damage circumscribed to the hippocampus, failed to acquire value-based contingencies, thus confirming that hippocampal engagement is necessary for task performance. Control experiments established that this impairment was not due to perceptual demands or memory load. Future research is needed to clarify the mechanisms by which the hippocampus contributes to value-based learning, but these findings point to a broader role for the hippocampus in goal-directed behaviors than previously appreciated.

Three Auxin Response Factors Promote Hypocotyl Elongation.

The hormone auxin regulates growth largely by affecting gene expression. By studying Arabidopsis (Arabidopsis thaliana) mutants deficient in AUXIN RESPONSE FACTORS (ARFs), we have identified three ARF proteins that are required for auxin-responsive hypocotyl elongation. Plants deficient in these factors have reduced responses to environmental conditions that increase auxin levels, including far-red-enriched light and high temperature. Despite having decreased auxin responses, the ARF-deficient plants responded to brassinosteroid and gibberellin, indicating that different hormones can act partially independently. Aux/IAA proteins, encoded by IAA genes, interact with ARF proteins to repress auxin response. Silencing expression of multiple IAA genes increased hypocotyl elongation, suggesting that Aux/IAA proteins modulate ARF activity in hypocotyls in a potential negative feedback loop.

Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer's disease.

Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease.

Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults.

Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO2), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy.

COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume.

BACKGROUND: Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. METHODS: Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. RESULTS: We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. LIMITATIONS: The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. CONCLUSION: Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.

UV-B detected by the UVR8 photoreceptor antagonizes auxin signaling and plant shade avoidance.

Plants detect different facets of their radiation environment via specific photoreceptors to modulate growth and development. UV-B is perceived by the photoreceptor UV RESISTANCE LOCUS 8 (UVR8). The molecular mechanisms linking UVR8 activation to plant growth are not fully understood, however. When grown in close proximity to neighboring vegetation, shade-intolerant plants initiate dramatic stem elongation to overtop competitors. Here we show that UV-B, detected by UVR8, provides an unambiguous sunlight signal that inhibits shade avoidance responses in Arabidopsis thaliana by antagonizing the phytohormones auxin and gibberellin. UV-B triggers degradation of the transcription factors PHYTOCHROME INTERACTING FACTOR 4 and PHYTOCHROME INTERACTING FACTOR 5 and stabilizes growth-repressing DELLA proteins, inhibiting auxin biosynthesis via a dual mechanism. Our findings show that UVR8 signaling is closely integrated with other photoreceptor pathways to regulate auxin signaling and plant growth in sunlight.

The Effectiveness of Remote Facilitation in Simulation-Based Pediatric Resuscitation Training for Medical Students.

OBJECTIVES: To assess the effectiveness of pediatric simulation by remote facilitation. We hypothesized that simulation by remote facilitation is more effective compared to simulation by an on-site facilitator. We defined remote facilitation as a facilitator remotely (1) introduces simulation-based learning and simulation environment, (2) runs scenarios, and (3) performs debriefing with an on-site facilitator. METHODS: A remote simulation program for medical students during pediatric rotation was implemented. Groups were allocated to either remote or on-site facilitation depending on the availability of telemedicine technology. Both groups had identical 1-hour simulation sessions with 2 scenarios and debriefing. Their team performance was assessed with behavioral assessment tool by a trained rater. Perception by students was evaluated with Likert scale (1-7). RESULTS: Fifteen groups with 89 students participated in a simulation by remote facilitation, and 8 groups with 47 students participated in a simulation by on-site facilitation. Participant demographics and previous simulation experience were similar. Both groups improved their performance from first to second scenario: groups by remote simulation (first [8.5 ± 4.2] vs second [13.2 ± 6.2], P = 0.003), and groups by on-site simulation (first [6.9 ± 4.1] vs second [12.4 ± 6.4], P = 0.056). The performance improvement was not significantly different between the 2 groups (P = 0.94). Faculty evaluation by students was equally high in both groups (7 vs 7; P = 0.65). CONCLUSIONS: A pediatric acute care simulation by remote facilitation significantly improved students' performance. In this pilot study, remote facilitation seems as effective as a traditional, locally facilitated simulation. The remote simulation can be a strong alternative method, especially where experienced facilitators are limited.

Less wiring, more firing: low-performing older adults compensate for impaired white matter with greater neural activity.

The reliable neuroimaging finding that older adults often show greater activity (over-recruitment) than younger adults is typically attributed to compensation. Yet, the neural mechanisms of over-recruitment in older adults (OAs) are largely unknown. Rodent electrophysiology studies have shown that as number of afferent fibers within a circuit decreases with age, the fibers that remain show higher synaptic field potentials (less wiring, more firing). Extrapolating to system-level measures in humans, we proposed and tested the hypothesis that greater activity in OAs compensates for impaired white-matter connectivity. Using a neuropsychological test battery, we measured individual differences in executive functions associated with the prefrontal cortex (PFC) and memory functions associated with the medial temporal lobes (MTLs). Using event-related functional magnetic resonance imaging, we compared activity for successful versus unsuccessful trials during a source memory task. Finally, we measured white-matter integrity using diffusion tensor imaging. The study yielded 3 main findings. First, low-executive OAs showed greater success-related activity in the PFC, whereas low-memory OAs showed greater success-related activity in the MTLs. Second, low-executive OAs displayed white-matter deficits in the PFC, whereas low-memory OAs displayed white-matter deficits in the MTLs. Finally, in both prefrontal and MTL regions, white-matter decline and success-related activations occurred in close proximity and were negatively correlated. This finding supports the less-wiring-more-firing hypothesis, which provides a testable account of compensatory over-recruitment in OAs.

Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis.

Sensory abnormalities such as numbness and paresthesias are often the earliest symptoms in neuroinflammatory diseases including multiple sclerosis. The increased production of various cytokines occurs in the early stages of neuroinflammation and could have detrimental effects on the central nervous system, thereby contributing to sensory and cognitive deficits. However, it remains unknown whether and when elevation of cytokines causes changes in brain structure and function under inflammatory conditions. To address this question, we used a mouse model for experimental autoimmune encephalomyelitis (EAE) to examine the effect of inflammation and cytokine elevation on synaptic connections in the primary somatosensory cortex. Using in vivo two-photon microscopy, we found that the elimination and formation rates of dendritic spines and axonal boutons increased within 7 d of EAE induction--several days before the onset of paralysis--and continued to rise during the course of the disease. This synaptic instability occurred before T-cell infiltration and microglial activation in the central nervous system and was in conjunction with peripheral, but not central, production of TNF-α. Peripheral administration of a soluble TNF inhibitor prevented abnormal turnover of dendritic spines and axonal boutons in presymptomatic EAE mice. These findings indicate that peripheral production of TNF-α is a key mediator of synaptic instability in the primary somatosensory cortex and may contribute to sensory and cognitive deficits seen in autoimmune diseases.