Integration Hub Research Articles

SLU7: A New Hub of Gene Expression Regulation-From Epigenetics to Protein Stability in Health and Disease.

SLU7 (Splicing factor synergistic lethal with U5 snRNA 7) was first identified as a splicing factor necessary for the correct selection of 3' splice sites, strongly impacting on the diversity of gene transcripts in a cell. More recent studies have uncovered new and non-redundant roles of SLU7 as an integrative hub of different levels of gene expression regulation, including epigenetic DNA remodeling, modulation of transcription and protein stability. Here we review those findings, the multiple factors and mechanisms implicated as well as the cellular functions affected. For instance, SLU7 is essential to secure liver differentiation, genome integrity acting at different levels and a correct cell cycle progression. Accordingly, the aberrant expression of SLU7 could be associated with human diseases including cancer, although strikingly, it is an essential survival factor for cancer cells. Finally, we discuss the implications of SLU7 in pathophysiology, with particular emphasis on the progression of liver disease and its possible role as a therapeutic target in human cancer.

A Functional Genomics View of Gibberellin Metabolism in the Cnidarian Symbiont Breviolum minutum.

Dinoflagellate inhabitants of the reef-building corals exchange nutrients and signals with host cells, which often benefit the growth of both partners. Phytohormones serve as central hubs for signal integration between symbiotic microbes and their hosts, allowing appropriate modulation of plant growth and defense in response to various stresses. However, the presence and function of phytohormones in photosynthetic dinoflagellates and their function in the holobionts remain elusive. We hypothesized that endosymbiotic dinoflagellates may produce and employ phytohormones for stress responses. Using the endosymbiont of reef corals Breviolum minutum as model, this study aims to exam whether the alga employ analogous signaling systems by an integrated multiomics approach. We show that key gibberellin (GA) biosynthetic genes are widely present in the genomes of the selected dinoflagellate algae. The non-13-hydroxylation pathway is the predominant route for GA biosynthesis and the multifunctional GA dioxygenase in B. minutum has distinct substrate preference from high plants. GA biosynthesis is modulated by the investigated bleaching-stimulating stresses at both transcriptional and metabolic levels and the exogenously applied GAs improve the thermal tolerance of the dinoflagellate. Our results demonstrate the innate ability of a selected Symbiodiniaceae to produce the important phytohormone and the active involvement of GAs in the coordination and the integration of the stress response.

Light, chromatin, action: nuclear events regulating light signaling in Arabidopsis.

The plant nucleus provides a major hub for environmental signal integration at the chromatin level. Multiple light signaling pathways operate and exchange information by regulating a large repertoire of gene targets that shape plant responses to a changing environment. In addition to the established role of transcription factors in triggering photoregulated changes in gene expression, there are eminent reports on the significance of chromatin regulators and nuclear scaffold dynamics in promoting light-induced plant responses. Here, we report and discuss recent advances in chromatin-regulatory mechanisms modulating plant architecture and development in response to light, including the molecular and physiological roles of key modifications such as DNA, RNA and histone methylation, and/or acetylation. The significance of the formation of biomolecular condensates of key light signaling components is discussed and potential applications to agricultural practices overviewed.

A Distributed Network for Multimodal Experiential Representation of Concepts.

Neuroimaging, neuropsychological, and psychophysical evidence indicate that concept retrieval selectively engages specific sensory and motor brain systems involved in the acquisition of the retrieved concept. However, it remains unclear which supramodal cortical regions contribute to this process and what kind of information they represent. Here, we used representational similarity analysis of two large fMRI datasets with a searchlight approach to generate a detailed map of human brain regions where the semantic similarity structure across individual lexical concepts can be reliably detected. We hypothesized that heteromodal cortical areas typically associated with the default mode network encode multimodal experiential information about concepts, consistent with their proposed role as cortical integration hubs. In two studies involving different sets of concepts and different participants (both sexes), we found a distributed, bihemispheric network engaged in concept representation, composed of high-level association areas in the anterior, lateral, and ventral temporal lobe; inferior parietal lobule; posterior cingulate gyrus and precuneus; and medial, dorsal, ventrolateral, and orbital prefrontal cortex. In both studies, a multimodal model combining sensory, motor, affective, and other types of experiential information explained significant variance in the neural similarity structure observed in these regions that was not explained by unimodal experiential models or by distributional semantics (i.e., word2vec similarity). These results indicate that during concept retrieval, lexical concepts are represented across a vast expanse of high-level cortical regions, especially in the areas that make up the default mode network, and that these regions encode multimodal experiential information.SIGNIFICANCE STATEMENT Conceptual knowledge includes information acquired through various modalities of experience, such as visual, auditory, tactile, and emotional information. We investigated which brain regions encode mental representations that combine information from multiple modalities when participants think about the meaning of a word. We found that such representations are encoded across a widely distributed network of cortical areas in both hemispheres, including temporal, parietal, limbic, and prefrontal association areas. Several areas not traditionally associated with semantic cognition were also implicated. Our results indicate that the retrieval of conceptual knowledge during word comprehension relies on a much larger portion of the cerebral cortex than previously thought and that multimodal experiential information is represented throughout the entire network.

Proteolytic control in ciliogenesis: Temporal restriction or early initiation?

Cellular processes are highly dependent on a dynamic proteome that undergoes structural and functional rearrangements to allow swift conversion between different cellular states. By inducing proteasomal degradation of inhibitory or stimulating factors, ubiquitylation is particularly well suited to trigger such transitions. One prominent example is the remodelling of the centrosome upon cell cycle exit, which is required for the formation of primary cilia - antenna-like structures on the surface of most cells that act as integrative hubs for various extracellular signals. Over the last decade, many reports on ubiquitin-related events involved in the regulation of ciliogenesis have emerged. Very often, these processes are considered to be initiated ad hoc, that is, directly before its effect on cilia biogenesis becomes evident. While such a temporal restriction may hold true for the majority of events, there is evidence that some of them are initiated earlier during the cell cycle. Here, we provide an overview of ubiquitin-dependent processes in ciliogenesis and discuss available data that indicate such an early onset of proteolytic regulation within preceding cell cycle stages.

Do Integrated Hub Models of Care Improve Mental Health Outcomes for Children Experiencing Adversity? A Systematic Review.

This review assesses the effectiveness of integrated primary health and social care hubs on mental health outcomes for children experiencing adversity and describes common integration dimensions of effective hubs.PubMed, OVID Medline and PyschINFO databases were systematically searched for relevant articles between 2006–2020 that met the inclusion criteria: (i) interventional studies, (ii) an integrated approach to mental health within a primary health care setting, (iii) validated measures of child mental health outcomes, and (iv) in English language.Of 5961 retrieved references, four studies involving children aged 0–12 years experiencing one or more adversities were included. Most children were male (mean: 60.5%), and Hispanic or African American (82.5%).Three studies with low-moderate risk of bias reported improvements in mental health outcomes for children experiencing adversity receiving integrated care. The only RCT in this review did not show significant improvements.The most common dimensions of effective integrated hubs based on the Rainbow Model of Integrated Care were clinical integration (including case management, patient-centred care, patient education, and continuity of care), professional integration, and organisational integration including co-location.These results suggest hubs incorporating effective integration dimensions could improve mental health outcomes for children experiencing adversity; however, further robust studies are required.Registered with Prospero: CRD42020206015.

As Data Flows Surge Data Infrastructure Groans

As Data Flows Surge Data Infrastructure Groans

Functional (ir)Relevance of Posterior Parietal Cortex during Audiovisual Change Detection.

The posterior parietal cortex (PPC) plays a key role in integrating sensory inputs from different modalities to support adaptive behavior. Neuronal activity in PPC reflects perceptual decision-making across behavioral tasks, but the mechanistic involvement of PPC is unclear. In an audiovisual change detection task, we tested the hypothesis that PPC is required to arbitrate between the noisy inputs from the two different modalities and help decide in which modality a sensory change occurred. In trained male mice, we found extensive single-neuron and population-level encoding of task-relevant visual and auditory stimuli, trial history, as well as upcoming behavioral responses. However, despite these rich neural correlates, which would theoretically be sufficient to solve the task, optogenetic inactivation of PPC did not affect visual or auditory performance. Thus, despite neural correlates faithfully tracking sensory variables and predicting behavioral responses, PPC was not relevant for audiovisual change detection. This functional dissociation questions the role of sensory- and task-related activity in parietal associative circuits during audiovisual change detection. Furthermore, our results highlight the necessity to dissociate functional correlates from mechanistic involvement when exploring the neural basis of perception and behavior.SIGNIFICANCE STATEMENT The posterior parietal cortex (PPC) is active during many daily tasks, but capturing its function has remained challenging. Specifically, it is proposed to function as an integration hub for multisensory inputs. Here, we tested the hypothesis that, rather than classical cue integration, mouse PPC is involved in the segregation and discrimination of sensory modalities. Surprisingly, although neural activity tracked current and past sensory stimuli and reflected the ongoing decision-making process, optogenetic inactivation did not affect task performance. Thus, we show an apparent redundancy of sensory and task-related activity in mouse PPC. These results narrow down the function of parietal circuits, as well as direct the search for those neural dynamics that causally drive perceptual decision-making.

Stochastic Optimal Operation Framework of an Integrated Methane-Based Zero-CO2 Energy Hub in Energy Markets

Energy hubs (EHs) are couplers between different energy carriers in smart grids. The optimal participation of these actors in energy markets (EMs) as active and helpful actors is essential. This paper presents a new structure of methane-based EH considering biomass fuel to participate in the EMs of electricity, heat, and natural gas (NG). For this purpose, we propose an optimal bidding framework for the EH as a MILP stochastic optimization problem. The EH does not inject any CO2 pollution into the air (zero-CO2) and converts it into valuable methane (CH4) fuel using the CH4 production unit. To model uncertain parameters, electricity market price, wind speed, and solar radiation, an LSTM-based model of deep learning is proposed for scenario generation. Moreover, the Kantorovich distance matrix method reduces the generated scenarios. Since the proposed EH structure is compatible with Finland's infrastructure, simulation studies using actual data of this country are performed on selected days. The results show that in addition to profitable operation, high flexibility, environmental friendliness, and high accuracy of uncertainty modeling, the EH has no dependence on the purchase of energy carriers.

5-HT7 receptors expressed in the mouse parafacial region are not required for respiratory chemosensitivity.

A brainstem homeostatic system senses CO2/H+ to regulate ventilation, blood gases and acid–base balance. Neurons of the retrotrapezoid nucleus (RTN) and medullary raphe are both implicated in this mechanism as respiratory chemosensors, but recent pharmacological work suggested that the CO2/H+ sensitivity of RTN neurons is mediated indirectly, by raphe‐derived serotonin acting on 5‐HT7 receptors. To investigate this further, we characterized Htr7 transcript expression in phenotypically identified RTN neurons using multiplex single cell qRT‐PCR and RNAscope. Although present in multiple neurons in the parafacial region of the ventrolateral medulla, Htr7 expression was undetectable in most RTN neurons (Nmb +/Phox2b+) concentrated in the densely packed cell group ventrolateral to the facial nucleus. Where detected, Htr7 expression was modest and often associated with RTN neurons that extend dorsolaterally to partially encircle the facial nucleus. These dorsolateral Nmb +/Htr7 + neurons tended to express Nmb at high levels and the intrinsic RTN proton detectors Gpr4 and Kcnk5 at low levels. In mouse brainstem slices, CO2‐stimulated firing in RTN neurons was mostly unaffected by a 5‐HT7 receptor antagonist, SB269970 (n = 11/13). At the whole animal level, microinjection of SB269970 into the RTN of conscious mice blocked respiratory stimulation by co‐injected LP‐44, a 5‐HT7 receptor agonist, but had no effect on CO2‐stimulated breathing in those same mice. We conclude that Htr7 is expressed by a minor subset of RTN neurons with a molecular profile distinct from the established chemoreceptors and that 5‐HT7 receptors have negligible effects on CO2‐evoked firing activity in RTN neurons or on CO2‐stimulated breathing in mice.Key points Neurons of the retrotrapezoid nucleus (RTN) are intrinsic CO2/H+ chemosensors and serve as an integrative excitatory hub for control of breathing.Serotonin can activate RTN neurons, in part via 5‐HT7 receptors, and those effects have been implicated in conferring an indirect CO2 sensitivity.Multiple single cell molecular approaches revealed low levels of 5‐HT7 receptor transcript expression restricted to a limited population of RTN neurons.Pharmacological experiments showed that 5‐HT7 receptors in RTN are not required for CO2/H+‐stimulation of RTN neuronal activity or CO2‐stimulated breathing.These data do not support a role for 5‐HT7 receptors in respiratory chemosensitivity mediated by RTN neurons.

Network Reconstruction and Modelling Made Reproducible with moped.

Mathematical modeling of metabolic networks is a powerful approach to investigate the underlying principles of metabolism and growth. Such approaches include, among others, differential-equation-based modeling of metabolic systems, constraint-based modeling and metabolic network expansion of metabolic networks. Most of these methods are well established and are implemented in numerous software packages, but these are scattered between different programming languages, packages and syntaxes. This complicates establishing straight forward pipelines integrating model construction and simulation. We present a Python package moped that serves as an integrative hub for reproducible construction, modification, curation and analysis of metabolic models. moped supports draft reconstruction of models directly from genome/proteome sequences and pathway/genome databases utilizing GPR annotations, providing a completely reproducible model construction and curation process within executable Python scripts. Alternatively, existing models published in SBML format can be easily imported. Models are represented as Python objects, for which a wide spectrum of easy-to-use modification and analysis methods exist. The model structure can be manually altered by adding, removing or modifying reactions, and gap-filling reactions can be found and inspected. This greatly supports the development of draft models, as well as the curation and testing of models. Moreover, moped provides several analysis methods, in particular including the calculation of biosynthetic capacities using metabolic network expansion. The integration with other Python-based tools is facilitated through various model export options. For example, a model can be directly converted into a CobraPy object for constraint-based analyses. moped is a fully documented and expandable Python package. We demonstrate the capability to serve as a hub for integrating reproducible model construction and curation, database import, metabolic network expansion and export for constraint-based analyses.

DC Energy Hubs for Integration of Community DERs, EVs, and Subway Systems

In this paper, a DC microgrid solution is proposed to mitigate the high penetration levels of distributed energy resources (DERs) and electric vehicles (EVs). The microgrid is designed to integrate the regenerative energy available as a result of trains braking at adjacent subway lines. Therefore, the proposed configuration not only helps the distribution network accommodate more renewable energy, but also reduces the energy consumption and peak demand associated with the nearby electrified transportation system. A framework for DC microgrid control has been developed and evaluated using a case study. The results prove the validity and effectiveness of the proposed control framework.

Fragmentation and performance dialogues in public management

PurposeLack of knowledge and performance information sharing between actors is one manifestation of fragmentation in public performance management. This study aims to understand what managerial means are used for connecting performance dialogues and how these means affect fragmentation in performance management.Design/methodology/approachIn this cross-sectional research design, the authors reviewed documents, interviewed public managers, observed workshops and held thematic discussions with public managers in one Finnish municipality. To analyze the empirical data, the authors used thematic analysis and both inductive and deductive research approaches.FindingsThe analysis revealed nine managerial means that public managers use for connecting performance dialogues to decrease fragmentation. These were (1) defining the division of labor between different dialogues, (2) assigning resources for performance dialogues, (3) generating convincing narratives for promoting collaboration, (4) providing the same performance information to collaborators, (5) building joint information systems, (6) establishing integrative performance dialogue hubs, (7) naming the gatekeepers, (8) offering training for dialogues and (9) synchronizing performance dialogues. Based on our findings, most of these means can preserve, increase or decrease fragmentation depending on their design.Originality/valueThe results of the study are valuable because the performance management literature has not investigated what managerial means are used to connect performance dialogues and how these means can preserve, increase or decrease fragmentation.

A Survey on the Usage and Evaluation of Exercise mhAPP among Urban Residents and Opinions of Relative Industry Experts over mhAPP Service in China-Residents and Experts in Guangzhou, Foshan and Changchun as Survey Respondents

Exercise mobile health application (mhAPP) is the integration hub of exercise and medical care, and a new health management tool. It can monitor the key physiological health indicators of the human body in exercise/quiet state, provide fitness courses, fitness/diet planning, and latest fitness consultation, etc., and has great potential value for the promotion of "Healthy China". In order to examine the current status of mhAPP services and the possible future application of mhAPP in big health services, this study investigated the acceptance, usage rate, brand selection and quality evaluation of mhAPP among Chinese urban residents, and the views of industry experts (doctors, fitness trainers, insurance managers and mhAPP developers) on the participation of mhAPP in industry services, aiming to provide a theoretical basis for mhAPP-mediated big health services in China.

An Integration Hub of Exercise and Medical Care – Mobile Health Application's Service Construction and Regulations Navigation in "Health China"

Exercise mobile health application (mhAPP) is the integration hub of exercise and medical care, a new health management tool. It can facilitate the monitoring of some physiological health indicators of the human body during exercise/quiet state, collect information on exercise and diet behavior, and even medical history, and quickly generate a "health portrait" of a group or an individual, which is of great significance for China's big health services. Based on China's market service demand, data exchange theory, Internet information security law, APP industry decree and regulation, and borrowing from the U.S. APP information management system, this study constructs a theoretical model of China's big health service system with mhAPP as data source, government-regulated cloud platform as data manager, and hospitals, CDCs, shopping malls, restaurants and other organizations as third-party data users, and designed ordinances and regulations to support its operation.

Arcuate Angiotensin II Increases Arterial Pressure via Coordinated Increases in Sympathetic Nerve Activity and Vasopressin Secretion.

The arcuate nucleus (ArcN) is an integrative hub for the regulation of energy balance, reproduction, and arterial pressure (AP), all of which are influenced by Angiotensin II (AngII); however, the cellular mechanisms and downstream neurocircuitry are unclear. Here, we show that ArcN AngII increases AP in female rats via two phases, both of which are mediated via activation of AngII type 1 receptors (AT1aRs): initial vasopressin-induced vasoconstriction, followed by slowly developing increases in sympathetic nerve activity (SNA) and heart rate (HR). In male rats, ArcN AngII evoked a similarly slow increase in SNA, but the initial pressor response was variable. In females, the effects of ArcN AngII varied during the estrous cycle, with significant increases in SNA, HR, and AP occurring during diestrus and estrus, but only increased AP during proestrus. Pregnancy markedly increased the expression of AT1aR in the ArcN with parallel substantial AngII-induced increases in SNA and MAP. In both sexes, the sympathoexcitation relied on suppression of tonic ArcN sympathoinhibitory neuropeptide Y (NPY) inputs, and activation of proopiomelanocortin (POMC) projections, to the paraventricular nucleus (PVN). Few or no NPY or POMC neurons expressed the AT1aR, suggesting that AngII increases AP and SNA at least in part indirectly via local interneurons, which express tyrosine hydroxylase (TH) and VGat (i.e., GABAergic). ArcN TH neurons release GABA locally, and central AT1aR and TH neurons mediate stress responses; therefore, we propose that TH AT1aR neurons are well situated to locally coordinate the regulation of multiple modalities within the ArcN in response to stress.

Uncovering the global task-modulated brain network in chunk decomposition with Chinese characters

Chunk decomposition, which requires the mental representation transformation in accordance with behavioral goals, is of vital importance to problem solving and creative thinking. Previous studies have identified that the frontal, parietal, and occipital cortex in the cognitive control network selectively activated in response to chunk tightness, however, functional localization strategy may overlook the interaction brain regions. Based on the notion of a global brain network, we proposed that multiple specialized regions have to be interconnected to maintain goal representation during the course of chunk decomposition. Therefore, the present study applied a beta-series correlation method to investigate interregional functional connectivity in the event-related design of chunk decomposition tasks using Chinese characters, which would highlight critical nodes irrespective to chunk tightness. The results reveal a network of functional hubs with highly within or between module connections, including the orbitofrontal cortex, superior/inferior parietal lobule, hippocampus, and thalamus. We speculate that the thalamus integrates information across modular as an integrative hub while the orbitofrontal cortex tracks the mental states of chunk decomposition on a moment-to-moment basis. The superior and inferior parietal lobule collaborate to manipulate the mental representation of chunk decomposition and the hippocampus associates the relationship between elements in the question and solution phase. Furthermore, the tightness of chunks is not only associated with different processors in visual systems but also leads to increased intermodular connections in right superior frontal gyrus and left precentral gyrus. To summary up, the present study first reveals the task-modulated brain network of chunk decomposition in addition to the tightness-related nodes in the frontal and occipital cortex.

The Pan-Clk/Dyrk Inhibitor Cirtuvivint (SM08502) Exposes Mechanistic Underpinnings of Alternative Splicing As a Therapeutic Vulnerability in Heme Malignancies

Mutations in spliceosomal genes are one of the most common classes of somatic alterations in patients with Myelodysplastic Syndrome (MDS) and occur across the entire spectrum of myeloid malignancies, including 10‒25% of patients with acute myeloid leukemia (AML). These mutations occur in higher proportions in AML subjects greater than 60 years of age, or when AML has transformed from an antecedent MDS. Spliceosomal gene mutations are implicated in the production of pathological RNA splicing patterns that block cell differentiation and maintain a myeloid precursor phenotype. This suggests deranged pre-mRNA splicing is a mechanistic determinant of many heme malignancies and, as such, has provoked interest in therapeutic modulation of pre-mRNA splicing as a treatment paradigm. The CLK/DYRK family of protein kinases has been recognized as an integration hub for signal transduction-dependent modulation of alternative pre-mRNA splice junction selection through direct phosphorylation of the serine/arginine-rich splicing factor (SRSF) splice junction enhancer-binding proteins. Thus, these kinases potentially represent a druggable intervention point in alternative splicing-dependent cancers. The isoquinoline SM08502 (cirtuvivint) is a potent ATP-competitive inhibitor of the Cdc2-like kinases (CLK1-4) and the dual specificity tyrosine phosphorylation-regulated kinases (DYRK1-4) with activity against only a minimal number of the remaining members of the CMGC-family kinases and the kinome as a whole. Here the consequence of pan-CLK/DYRK kinase inhibition on cell viability and tumorigenicity was evaluated across a panel of human tumor-derived AML, DLBCL, MCL, myeloma, T-ALL, and CML/CLL models. EC 50s in response to cirtuvivint ranged from 0.014 μM‒0.495 μM in 4-day in vitro cell viability assays, with low-dose responders enriched in subsets of AML, myeloma, DLBCL, MCL and T-ALL. Cell viability EC 50s were associated with induction of programed cell death at drug exposures that inhibited accumulation of phosphorylated SRSF proteins and the anti-apoptotic protein MCL-1. To directly evaluate the contribution of CLK/DYRK kinases to alternative splicing profiles, high-depth RNAseq analysis was performed across 4 cell lines (3 acute myeloid leukemia cell lines and 1 mantle cell lymphoma cell line) +/- a 6-hour exposure to 1µM cirtuvivint. Both baseline and drug-induced changes in alternative splicing events (ASEs) were measured using a multivariate analysis of splicing transcripts (rMATS). The frequency of cirtuvivint-induced ASEs was approximately 20% of total detected ASEs. Concordant drug-induced ASEs among the tested cell lines were in genes enriched in pathways known to drive oncogenesis in hematopoietic lineages, including the MAP kinase and mTOR signaling pathways. Tumor growth inhibition assays in immunocompromised mice showed a range of model-specific responses, including tumor stasis and partial to complete tumor regression at clinically relevant exposures. A cell-based synthetic-lethal screen of cirtuvivint across 36 small molecule inhibitors identified multiple BCL-2 inhibitors among the most prominent synergistic combinations. Consistent with this, combination of the BCL-2 inhibitor venetoclax with cirtuvivint was sufficient to induce tumor regressions in AML xenograft models (KG-1 and HL-60) that were resistant to either single-agent drug at the same concentrations. These observations support further evaluation of CLK/DYRK inhibitors as a therapeutic strategy for heme malignancies dependent upon alternative pre-mRNA splicing. DisclosuresBossard: Biosplice Therapeutics: Current Employment. McMillan: Prizer: Ended employment in the past 24 months. Beaupre: Pfizer: Ended employment in the past 24 months. White: Pfizer: Ended employment in the past 24 months.

NAD redox monitoring with the genetically encoded fluorescent biosensor Peredox-mCherry.

NAD status acts as an integration hub of plant cell metabolism, signalling, and the environment, but assessing its in situ dynamics has remained challenging using conventional analytical methods. The genetically encoded fluorescent biosensor, Peredox-mCherry, reports on the NADH:NAD+ ratio by coupling the fluorescence intensity of a tSapphire domain to binding of NADH or NAD+ to two T-Rex domains.

Transcranial Direct Current Stimulation Over the Right Anterior Temporal Lobe Does Not Modulate False Recognition.

Non-invasive transcranial direct current stimulation (tDCS) over the left anterior temporal lobe (ATL) has been shown to cause a reduction in the rate of false memories with semantically related words. Such a reduction seems to be specific to false memories induced by the study of associative lists, but is not observed when the studied lists are categorical in nature. These findings are interpreted as evidence that the left ATL functions as an integration hub that is crucial for the binding of semantic information into coherent representations of concepts. In order to investigate whether the right ATL might also contribute to semantic integration in the processing of verbal associative material, a follow-up tDCS study was conducted with the stimulation at study lateralized on the right ATL. A sample of 75 undergraduate students participated in an experiment in which they studied 8 associative lists and 8 categorical lists. One third of the participants studied all their word lists under anodal stimulation, another third studied under cathodal stimulation and the other third under sham stimulation. Results showed that stimulation of the right ATL by tDCS does not modulate false recognition for either association-related critical words or category-related critical words. These results provide preliminary support to views positing asymmetric connectivity between the anterior temporal lobes and the semantic representational network, and provide evidence for understanding bilateral brain dynamics and the nature of semantically induced memory distortions.