Endogenous Cues Research Articles

Exploring the Space-Calorie Association: Preliminary Evidence from Reaction Time Performance.

The present study was designed to investigate the representation of calorie levels in space. Previously an association between numerical magnitude and space has been established, namely, the Spatial Numerical Association of Response Codes (SNARC) effect. The spatial-numerical association reveals representation of smaller and larger numbers by the left and right sides, respectively. In addition, previous studies showed that spatial arrangement of foods in space affects the food selection behavior. In three experiments, the presence of an association between calorie magnitude and space was tested to understand how it could potentially affect food selection behavior. Reaction times were recorded to investigate the speed of information processing. In Experiment 1, locations of low and high calorie food stimuli were (in)congruent in terms of the space-calorie association. In Experiment 2, endogenous spatial cues were used to bias attention to investigate if this bias would lead to formation of the space-calorie association. Finally, Experiment 3 investigated whether green and red colors evoke approach or avoidance behavior and prevent formation of the space-calorie association. In all experiments, results revealed lack of an association between space and calorie, that is, presenting low/high calorie items on the left/right hemispace, respectively, did not modulate the processing speed.

Perinatal development of innate immune topology.

At the transition from intrauterine to postnatal life, drastic alterations are mirrored by changes in cellular immunity. These changes are in part immune cell intrinsic, originate in the replacement of fetal cells, or result from global regulatory mechanisms and adaptation to changes in the tissue microenvironment. Overall, longer developmental trajectories are intersected by events related to mother-infant separation, birth cues, acquisition of microbiota and metabolic factors. Perinatal alterations particularly affect immune niches, where structures with discrete functions meet, the intestinal mucosa, epidermis and lung. Accordingly, the following questions will be addressed in this review:How does the preprogrammed development supported by endogenous cues, steer innate immune cell differentiation, adaptation to tissue structures, and immunity to infection?How does the transition at birth impact on tissue immune make-up including its topology?How do postnatal cues guide innate immune cell differentiation and function at immunological niches?

Temporal and spatial topography of cell proliferation in cancer.

3122 Background: Tumors are complex ecosystems where exogenous and endogenous cues are integrated to either stimulate or inhibit cancer cell proliferation. However, the nature of these complex cell cycle states, their spatial organization, response to perturbation, and implications for clinical outcomes, are poorly characterized in tumor tissues. Methods: We used multiplexed tissue imaging to develop a robust classifier of proliferation, the multivariate proliferation index (MPI), using 513 unique tumors across five cancer types. Next, we used dimensionality reduction analysis to assess how the patterns of cell cycle protein expression in tumors were altered in response to perturbation. Results: The MPI outperforms single markers, like Ki67, when classifying proliferative index across diverse tumor types and reveals the proliferative architecture of tumors in situ. We find that proliferative and non-proliferative cancer cells are organized across microscopic (cell-to-cell) and macroscopic (tissue-level) scales. Both domains are reshaped by therapy, and local clusters of proliferative and non-proliferative tumor cells preferentially neighbor distinct tumor-infiltrating immune cells. We further phenotyped non-proliferating cancer cells using markers of quiescent cancer cells, cancer stem cells, and dormant cancer cells. We found that these types of non-proliferating cancer cells can occupy distinct regions within the same primary tumor. In high-dimensional marker space, populations of proliferative cancer cells express canonical patterns of cell cycle protein markers, a property we refer to as “cell cycle coherence”. Untreated tumors exist in a continuum of coherence states, ranging from optimal coherence, akin to freely cycling cells in culture, to reduced coherence characterized by either cell cycle polarization or non-canonical marker expression. Coherence can be stereotypically altered by induction and abrogation of mitogen signaling in a HER2-driven model of breast cancer. Cell cycle coherence is modulated by neoadjuvant therapy in patients with localized breast cancer, and coherence is associated with disease-free survival after adjuvant therapy in patients with colorectal cancer, mesothelioma and glioblastoma. Conclusions: The MPI robustly defines proliferating and non-proliferating cells in tissues, with immediate implications for clinical practice and research. The coherence metrics capture the diversity of post-treatment cell cycle states directly in clinical samples, a fundamental step in advancing precision medicine. More broadly, replacing binary metrics with multivariate traits provides a quantitative framework to study temporal processes from fixed static images and to investigate the rich spatial biology of human cancers.

037 Subjective sleep and objective cognition in middle-aged and older adults: Does sex matter?

Abstract Introduction Worse sleep has been linked to cognitive dysfunction in aging populations. There are known sex differences in the prevalence and presentation of both sleep disturbance and cognitive impairment, but research investigating sex differences in the associations between sleep and objective cognition is limited and inconclusive. We examined sex as a moderator of associations between self-reported sleep and objective cognitive performance in middle-aged/older adults. Methods Sixty-four adults aged 50+ (Mage= 63.8, SD=7.7; 33 men/31 women) who were cognitively healthy (no mild cognitive impairment, dementia or neurological disorders) completed an online survey (via Qualtrics) measuring self-reported sleep (Pittsburgh Sleep Quality Index; PSQI). Participants completed online cognitive tasks (via Inquisit) measuring inhibition (Stroop task; interference reaction time scores), attentional orienting (Posner Endogenous Cueing Task; reaction time difference between invalidly cued and validly cued trials), and working memory (Sternberg task; proportion correct). Multiple regressions examined whether PSQI subscores (sleep quality, sleep duration, sleep efficiency) were independently associated with or interacted with sex in their associations with cognition, controlling for age and education. Results Sex interacted with sleep quality in the association with endogenous attentional orienting (p=.01, R-squared=.10). Specifically, worse sleep quality was associated with worse attentional orienting in women (B=22.73, SE=9.53, p=.02) but not men (p=.24). Sex interacted with PSQI-sleep duration (p=.03, R-squared=.08) and PSQI-sleep efficiency (p=.03, R-squared=.08) in the association with inhibition performance. Specifically, worse sleep duration (B=235.28, SE=77.51, p=.004) and sleep efficiency (B=211.73, SE=68.70, p=.003) were associated with worse interference scores in men but not women (ps>.05). No variables were associated with working memory. Conclusion In middle-aged and older adults, sex moderates associations between self-reported sleep and objective cognition, depending on the sleep parameter and cognitive ability assessed. Findings suggest that women are more vulnerable to the effects of poor sleep quality on spatial attention, whereas men are more vulnerable to the effects of shorter sleep duration and worse overall sleep fragmentation on ability to inhibit task-irrelevant stimuli. Future studies should investigate sex-specific associations between sleep and cognition over time in order to better understand the prospective trajectories of these processes during aging. Support (if any):

Auxin-induced AUXIN RESPONSE FACTOR4 activates APETALA1 and FRUITFULL to promote flowering in woodland strawberry

Flowering time is known to be regulated by numerous pathways, such as the autonomous, gibberellin, aging, photoperiod-mediated, and vernalization pathways. These regulatory mechanisms involve both environmental triggers and endogenous hormonal cues. Additional flowering control mechanisms mediated by other phytohormones, such as auxin, are less well understood. We found that in cultivated strawberry (Fragaria × ananassa), the expression of auxin response factor4 (FaARF4) was higher in the flowering stage than in the vegetative stage. Overexpression of FaARF4 in Arabidopsis thaliana and woodland strawberry (Fragaria vesca) resulted in transgenic plants flowering earlier than control plants. In addition, FveARF4-silenced strawberry plants showed delayed flowering compared to control plants, indicating that FaARF4 and FveARF4 function similarly in regulating flowering. Further studies showed that ARF4 can bind to the promoters of the floral meristem identity genes APETALA1 (AP1) and FRUITFULL (FUL), inducing their expression and, consequently, flowering in woodland strawberry. Our studies reveal an auxin-mediated flowering pathway in strawberry involving the induction of ARF4 expression.

Precocious sexual maturation: Unravelling the mechanisms of pubertal onset through clinical observations.

Puberty is a crucial biological process normally occurring at a specific time during the lifespan, during which sexual and somatic maturation are completed, and reproductive capacity is reached. Pubertal timing is not only determined by genetics, but also by endogenous and environmental cues, including nutritional and metabolic signals. During the last decade, we have learned much regarding the essential roles of kisspeptins and the neuropeptide pathways that converge on these neurones to modulate kisspeptin signalling, as well as neurokinin B and dynorphin, the co-transmitters of Kiss1 neurones in the arcuate nucleus, and the effects of melanocortins on puberty. Indeed, melanocortins are involved in transmitting the regulatory actions of metabolic cues on pubertal maturation. Intracellular metabolic sensors, such as the AMP-activated protein kinase and the fuel-sensing deacetylase SIRT1, have been shown to contribute to puberty. Further understanding of these signals and regulatory circuits will help uncover the intimacies of the central control of puberty, as well as how alterations in metabolic status, ranging from undernutrition to obesity, affect the pubertal process. Precocious puberty is rare and has a clear female predominance. Central precocious puberty (CPP) is diagnosed when premature activation of the hypothalamic-pituitary axis occurs. Its causes are heterogeneous, with alterations of the central nervous system being of special interest, and with environmental factors also playing a role in some cases. During the last decade, several mutations in different genes (including KISS1, KISS1R, MKRN3 and DLK1) that cause CPP have been discovered. Loss-of-function mutations in MKRN3 are the most common monogenic cause of CPP known to date. Here, we review and update what is known regarding the genotype-phenotype relationship in patients with CPP.

Repeated application of the covert shift of attention task improves endogenous but not exogenous attention in patients with unilateral visuospatial inattention

BackgroundMost neglect treatment studies focus on automatic re-orientation procedures, assuming a deficit in automatic processes. We compare an automatic- and a controlled procedure, using the endogenous and exogenous variants of Posner’s covert shift of attention task. MethodIn two experiments, neglect patients and patients with a right hemispherical stroke without neglect performed three blocks of Posner’s covert shift of attention task (Posner Task) on two days. In Study 1 we used endogenous cues, in Study 2, exogenous cues. ResultsIn the endogenous task, neglect patients improved significantly with valid left-sided cues between block 1 and 2 on Day 1, subsequently showing a plateauing. They also showed a gradual improvement on invalid trials on both days. In the exogenous condition, all participants responded only increasingly faster on trials with a long stimulus onset asynchrony. Practicing on both tasks led to fewer omissions for left-sided targets, minimally in the exogenous and clearly in the endogenous condition. ConclusionIn line with prior neuroanatomical studies, our study shows that practicing an endogenous, but not an exogenous, visuospatial attention task leads to significant improvements in neglect patients, especially for invalid trials, suggesting that neglect treatments based on top-down strategies should be given more attention.

What signals the glyoxalase pathway in plants?

Glyoxalase (GLY) system, comprising of GLYI and GLYII enzymes, has emerged as one of the primary methylglyoxal (MG) detoxification pathways with anindispensable role during abiotic and biotic stresses. MG homeostasis is indeed very closely guarded by the cell as its higher levels are cytotoxic for the organism. The dynamic responsiveness of MG-metabolizing GLY pathway to both endogenous cues such as, phytohormones, nutrient status, etc., as well as external environmental fluctuations (abiotic and biotic stresses) indicates that a tight regulation occurs in the cell to maintain physiological levels of MG in the system. Interestingly, GLY pathway is also manipulated by its substrates and reaction products. Hence, an investigation of signalling and regulatory aspects of GLY pathway would be worthwhile. Herein, we have attempted to converge all known factors acting as signals or directly regulating GLYI/II enzymes in plants. Further, we also discuss how crosstalk between these different signal molecules might facilitate the regulation of glyoxalase pathway. We believe that MG detoxification is controlled by intricate mechanisms involving a plethora of signal molecules.

Two chemically distinct root lignin barriers control solute and water balance

Lignin is a complex polymer deposited in the cell wall of specialised plant cells, where it provides essential cellular functions. Plants coordinate timing, location, abundance and composition of lignin deposition in response to endogenous and exogenous cues. In roots, a fine band of lignin, the Casparian strip encircles endodermal cells. This forms an extracellular barrier to solutes and water and plays a critical role in maintaining nutrient homeostasis. A signalling pathway senses the integrity of this diffusion barrier and can induce over-lignification to compensate for barrier defects. Here, we report that activation of this endodermal sensing mechanism triggers a transcriptional reprogramming strongly inducing the phenylpropanoid pathway and immune signaling. This leads to deposition of compensatory lignin that is chemically distinct from Casparian strip lignin. We also report that a complete loss of endodermal lignification drastically impacts mineral nutrients homeostasis and plant growth.

The BOP-type co-transcriptional regulator NODULE ROOT1 promotes stem secondary growth of the tropical Cannabaceae tree Parasponia andersonii.

SummaryTree stems undergo a massive secondary growth in which secondary xylem and phloem tissues arise from the vascular cambium. Vascular cambium activity is driven by endogenous developmental signalling cues and environmental stimuli. Current knowledge regarding the genetic regulation of cambium activity and secondary growth is still far from complete. The tropical Cannabaceae tree Parasponia andersonii is a non‐legume research model of nitrogen‐fixing root nodulation. Parasponia andersonii can be transformed efficiently, making it amenable for CRISPR‐Cas9‐mediated reverse genetics. We considered whether P. andersonii also could be used as a complementary research system to investigate tree‐related traits, including secondary growth. We established a developmental map of stem secondary growth in P. andersonii plantlets. Subsequently, we showed that the expression of the co‐transcriptional regulator PanNODULE ROOT1 (PanNOOT1) is essential for controlling this process. PanNOOT1 is orthologous to Arabidopsis thaliana BLADE‐ON‐PETIOLE1 (AtBOP1) and AtBOP2, which are involved in the meristem‐to‐organ‐boundary maintenance. Moreover, in species forming nitrogen‐fixing root nodules, NOOT1 is known to function as a key nodule identity gene. Parasponia andersonii CRISPR‐Cas9 loss‐of‐function Pannoot1 mutants are altered in the development of the xylem and phloem tissues without apparent disturbance of the cambium organization and size. Transcriptomic analysis showed that the expression of key secondary growth‐related genes is significantly down‐regulated in Pannoot1 mutants. This allows us to conclude that PanNOOT1 positively contributes to the regulation of stem secondary growth. Our work also demonstrates that P. andersonii can serve as a tree research system.

Nutations in Plant Shoots: Endogenous and Exogenous Factors in the Presence of Mechanical Deformations.

We present a three-dimensional morphoelastic rod model capable to describe the morphogenesis of growing plant shoots driven by differential growth. We discuss the evolution laws for endogenous oscillators, straightening mechanisms, and reorientations to directional cues, such as gravitropic reactions governed by the avalanche dynamics of statoliths. We use this model to investigate the role of elastic deflections due to gravity loading in circumnutating plant shoots. We show that, in the absence of endogenous cues, pendular and circular oscillations arise as a critical length is attained, thus suggesting the occurrence of an instability triggered by exogenous factors. When also oscillations due to endogenous cues are present, their weight relative to those associated with the instability varies in time as the shoot length and other biomechanical properties change. Thanks to the simultaneous occurrence of these two oscillatory mechanisms, we are able to reproduce a variety of complex behaviors, including trochoid-like patterns, which evolve into circular orbits as the shoot length increases, and the amplitude of the exogenous oscillations becomes dominant.

Limited flexibility in departure timing of migratory passerines at the East-Mediterranean flyway

The rapid pace of current global warming lead to the advancement of spring migration in the majority of long-distance migratory bird species. While data on arrival timing to breeding grounds in Europe is plentiful, information from the African departure sites are scarce. Here we analysed changes in arrival timing at a stopover site in Israel and any links to Enhanced Vegetation Index (EVI) on the species-specific African non-breeding range in three migratory passerines between 2000–2017. Differences in wing length between early and late arriving individuals were also examined as a proxy for migration distance. We found that male redstart, but not females, advanced arrival to stopover site, but interestingly, not as a response to EVI phenology. Blackcap and barred warbler did not shift arrival timing significantly, although the arrival of blackcap was dependent on EVI. Barred warbler from the early arrival phase had longer wings, suggesting different populations. Our study further supports the existence species-specific migration decisions and inter-sexual differences, which may be triggered by both exogenous (local vegetation condition) and endogenous cues. Given rapid rate of changes in environmental conditions at higher latitudes, some migrants may experience difficulty in the race to match global changes to ensure their survival.

IL-6 promotes MYC-induced B cell lymphomagenesis independent of STAT3.

The inflammatory cytokine IL-6 is known to play a causal role in the promotion of cancer, although the underlying mechanisms remain to be completely understood. Interplay between endogenous and environmental cues determines the fate of cancer development. The Eμ-myc transgenic mouse expresses elevated levels of c-Myc in the B cell lineage and develops B cell lymphomas with associated mutations in p53 or other genes linked to apoptosis. We generated Eμ-myc mice that either lacked the IL-6 gene, or lacked the STAT3 gene specifically in B cells to determine the role of the IL-6/JAK/STAT3 pathway in tumor development. Using the Eμ-myc lymphoma mouse model, we demonstrate that IL-6 is a critical tumor promoter during early stages of B cell lymphomagenesis. IL-6 is shown to inhibit the expression of tumor suppressors, notably BIM and PTEN, and this may contribute to advancing MYC-driven B cell tumorigenesis. Several miRNAs known to target BIM and PTEN are upregulated by IL-6 and likely lead to the stable suppression of pro-apoptotic pathways early during the tumorigenic process. STAT3, a classical downstream effector of IL-6, appears dispensable for Eμ-myc driven lymphomagenesis. We conclude that the growth-promoting and anti-apoptotic mechanisms activated by IL-6 are critically involved in Eμ-myc driven tumor initiation and progression, but the B cell intrinsic expression of STAT3 is not required.

Stomata: the holey grail of plant evolution

Stomata: the holey grail of plant evolution

PHOSPHATIDYLETHANOLAMINE-BINDING PROTEINS: the conductors of dual reproduction in plants with vegetative storage organs.

Geophytes, the plants that form vegetative storage organs, are characterized by a dual reproduction system, in which vegetative and sexual propagation are tightly regulated to ensure fitness in harsh climatic conditions. Recent findings highlight the role of the PEBP (PHOSPHATIDYLETHANOLAMINE-BINDING PROTEIN) gene family in geophytes as major players in the molecular cascades underlying both types of reproduction. In this review, we briefly explain the life cycle and reproduction strategies of different geophytes and what is known about the physiological aspects related to these processes. Subsequently, an in-depth overview is provided of the molecular and genetic pathways driving these processes. In the evolution of plants, the PEBP gene family has expanded, followed by neo- and subfunctionalization. Careful characterization revealed that differential expression and differential protein complex formation provide the members of this gene family with unique functions, enabling them to mediate the crosstalk between the two reproductive events in geophytes in response to environmental and endogenous cues. Taking all these studies into account, we propose to regard the PEBPs as conductors of geophyte reproductive development.

Therapeutic induction of tolerogenic dendritic cells via aryl hydrocarbon receptor signaling.

Dendritic cells (DCs) are potent antigen-presenting cells (APCs), which sample the exogenous and endogenous cues to control adaptive immunity, balancing effector and regulatory components of the immune response. Multiple subsets of DCs, such as plasmacytoid and conventional DCs, have been defined based on specific phenotypic markers, functions and regulatory transcriptional programs. Tolerogenic DCs (tolDCs) have been functionally defined based on their ability to expand the regulatory T-cell compartment and suppress immune responses. However, it is still unclear whether tolDCs represent a homogeneous population, a specific DC subset and/or a heterogeneous collection of DC activation/maturation states. The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) has been shown to control transcriptional programs associated to tolDCs. In this review, we discuss the role of AHR in the control of tolDCs, and also AHR-targeted approaches for the therapeutic induction of tolDCs in autoimmune diseases and allergy.

Auxin-Regulated Lateral Root Organogenesis.

Plant fitness is largely dependent on the root, the underground organ, which, besides its anchoring function, supplies the plant body with water and all nutrients necessary for growth and development. To exploit the soil effectively, roots must constantly integrate environmental signals and react through adjustment of growth and development. Important components of the root management strategy involve a rapid modulation of the root growth kinetics and growth direction, as well as an increase of the root system radius through formation of lateral roots (LRs). At the molecular level, such a fascinating growth and developmental flexibility of root organ requires regulatory networks that guarantee stability of the developmental program but also allows integration of various environmental inputs. The plant hormone auxin is one of the principal endogenous regulators of root system architecture by controlling primary root growth and formation of LR. In this review, we discuss recent progress in understanding molecular networks where auxin is one of the main players shaping the root system and acting as mediator between endogenous cues and environmental factors.

Single-Case Neuropsychological Assessment of a Patient with a Posterior Parietal Lesion Using Behavioral Testing and Resting-State fMRI

This study integrated functional connectivity measures using resting-state fMRI and behavioral data from a single-case observation of patient (PER) one year after right-hemispheric hemorrhage in the intraparietal sulcus and superior parietal lobule (IPS/SPL). PER showed no sign of clinical neglect. Her behavioral performance in the visuo-manual pointing task and in the letter discrimination task under conditions of endogenous and exogenous attentional cueing was compared between the left (affected) and right (unaffected/control) peripheral visual fields. The resting-state fMRI demonstrated an imbalance between the right and left hemispheric frontoparietal functional connectivity within the dorsal attentional and motor networks. Although the frontal and occipital cortices were not structurally damaged, specific fronto-occipital functional connectivity was imbalanced, which was strongly associated with the behavioral changes. First, the activity in the right frontal eye field showed weaker correlations with the activity in the right inferior occipital area compared to the correlation with the activity in the left inferior occipital area. This imbalanced fronto-occipital functional connectivity was accompanied by a specific impairment in endogenous covert attention in the left visual field. Second, the activity within M1 in both hemispheres showed weaker correlations with the activity of the right cuneus compared to the correlation with the activity in the left cuneus. The imbalanced fronto-occipital functional connectivity was associated with the impairment of the reaching movement of the left and right hands towards the left visual field (optic ataxia). Altogether, our results showed that a lesion to the posterior parietal cortex affects the relationship between distal regions underlying the sensorimotor and attentional abilities

Convergence and Divergence of Sugar and Cytokinin Signaling in Plant Development.

Plants adjust their growth and development through a sophisticated regulatory system integrating endogenous and exogenous cues. Many of them rely on intricate crosstalk between nutrients and hormones, an effective way of coupling nutritional and developmental information and ensuring plant survival. Sugars in their different forms such as sucrose, glucose, fructose and trehalose-6-P and the hormone family of cytokinins (CKs) are major regulators of the shoot and root functioning throughout the plant life cycle. While their individual roles have been extensively investigated, their combined effects have unexpectedly received little attention, resulting in many gaps in current knowledge. The present review provides an overview of the relationship between sugars and CKs signaling in the main developmental transition during the plant lifecycle, including seed development, germination, seedling establishment, root and shoot branching, leaf senescence, and flowering. These new insights highlight the diversity and the complexity of the crosstalk between sugars and CKs and raise several questions that will open onto further investigations of these regulation networks orchestrating plant growth and development.

Chemo-Mechanical Modulation of Cell Motions Using DNA Nanosprings.

Cell motions such as migration and change in cellular morphology are essential activities for multicellular organism in response to environmental stimuli. These activities are a result of coordinated clustering/declustering of integrin molecules at the cell membrane. Here, we prepared DNA origami nanosprings to modulate cell motions by targeting the clustering of integrin molecules. Each nanospring was modified with arginyl-glycyl-aspartic acid (RGD) domains with a spacing such that when the nanospring is coiled, the RGD ligands trigger the clustering of integrin molecules, which changes cell motions. The coiling or uncoiling of the nanospring is controlled, respectively, by the formation or dissolution of an i-motif structure between neighboring piers in the DNA origami nanodevice. At slightly acidic pH (<6.5), the folding of the i-motif leads to the coiling of the nanospring, which inhibits the motion of HeLa cells. At neutrality (pH 7.4), the unfolding of the i-motif allows cells to resume mechanical movement as the nanospring becomes uncoiled. We anticipate that this pH-responsive DNA nanoassembly is valuable to inhibit the migration of metastatic cancer cells in acidic extracellular environment. Such a chemo-mechanical modulation provides a new mechanism for cells to mechanically respond to endogenous chemical cues.