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"The fields of international education and study abroad are inherently conducive to new experiences and attentiveness to the moment. However, they have not been fully explored as areas of interest for the integration of contemplative practices. We present a case study of a group of 10 respondents, eighteen months after returning to the US from a study-abroad program in France. The scaffolded curriculum of the program centered around mindfulness and the use of the five senses to engage with and learn about the host culture. During the program, students practiced techniques, reflected collectively and metacognitively in writing assignments. More than a year after the study-abroad program, ten of the thirteen students volunteered answers expounding on their connection to mindfulness. Content analysis of their answers indicates that students perceive a positive impact of mindfulness on their personal, professional, and academic lives. Notably, results indicate that students may have experienced an increased awareness of and attentiveness to their surroundings, improved interoception and metacognition, a greater ability to connect with those around them, and an enhanced capacity for recall and memory."

The Syrian conflict has resulted in the most significant refugee crisis since World War II. Current estimates suggest there are over 13.5 million Syrians in need of comprehensive humanitarian assistance as a direct result of the conflict. These humanitarian needs include mental health services to address the elevated rates of psychiatric disorders in this population. Towards this end, the Syrian American Medical Society conducted its inaugural mental health mission trip to Lebanon and Jordan from June to July 2019 to advance the state of mental health care for displaced Syrians. Following two weeks of trainings by international experts in trauma psychology, the mission concluded with a two-day scientific symposium, identifying two key elements for the advancement of humanitarian mental health care: 1) the need for community-based mental health services, and 2) the importance of transitioning from a crisis-response model in humanitarian mental health towards a model of resilience and post-traumatic growth.

Animal research has recognized the role of the sensory cortex in fear memory and two key underlying mechanisms—pattern separation and tuning shift. We interrogated these mechanisms in the human sensory cortex in an olfactory differential conditioning study with a delayed (9-day) retention test. Combining affective appraisal and olfactory psychophysics with functional magnetic resonance imaging (fMRI) multivoxel pattern analysis and voxel-based tuning analysis over a linear odor-morphing continuum, we confirmed affective and perceptual learning and memory and demonstrated associative plasticity in the human olfactory (piriform) cortex. Specifically, the piriform cortex exhibited immediate and lasting enhancement in pattern separation (between the conditioned stimuli/CS and neighboring non-CS) and late-onset yet lasting tuning shift towards the CS, especially in anxious individuals. These findings highlight an evolutionarily conserved sensory cortical system of fear memory, which can underpin sensory encoding of fear/threat and confer a sensory mechanism to the neuropathophysiology of anxiety.

The default mode network (DMN) is the most prominent intrinsic connectivity network, serving as a key architecture of the brain’s functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly, alpha (8-12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition (HD) alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous EEG-fMRI, we demonstrated that α-tACS (vs. sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can upregulate the DMN further highlights an effective non-invasive intervention to normalize DMN functioning in various disorders.Significance StatementIn the brain’s functional organization, the default mode network (DMN) represents a key architecture, whose dysregulation is involved in a host of major neuropsychiatric disorders. However, insights into the regulation of the DMN remain scarce. Through neural synchrony, the alpha-frequency oscillation represents another key underpinning of the brain’s organization and is thought to share an inherent interdependence with the DMN. Here, we demonstrated that transcranial alternating current stimulation of alpha oscillations (α-tACS) not only augmented alpha activity but also strengthened connectivity of the DMN, with the former serving as a mediator of the latter. These findings reveal that alpha oscillations can support DMN functioning. In addition, they identify an effective non-invasive approach to regulate the DMN via α-tACS.

People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.3 of SBOL Visual, which builds on the prior SBOL Visual 2.2 in several ways. First, the specification now includes higher-level “interactions with interactions,” such as an inducer molecule stimulating a repression interaction. Second, binding with a nucleic acid backbone can be shown by overlapping glyphs, as with other molecular complexes. Finally, a new “unspecified interaction” glyph is added for visualizing interactions whose nature is unknown, the “insulator” glyph is deprecated in favor of a new “inert DNA spacer” glyph, and the polypeptide region glyph is recommended for showing 2A sequences.

People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.2 of SBOL Visual, which builds on the prior SBOL Visual 2.1 in several ways. First, the grounding of molecular species glyphs is changed from BioPAX to SBO, aligning with the use of SBO terms for interaction glyphs. Second, new glyphs are added for proteins, introns, and polypeptide regions (e. g., protein domains), the prior recommended macromolecule glyph is deprecated in favor of its alternative, and small polygons are introduced as alternative glyphs for simple chemicals.

Anomalies in default mode network (DMN) activity and alpha (8-12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that alpha oscillations support DMN functioning via inter-regional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of alpha deficits in the visual-cortex-DMN system in PTSD. Human patients with PTSD (N = 25) and two control groups—patients with Generalized Anxiety Disorder (GAD; N = 24) and healthy controls (HC; N = 20)—underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical alpha activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA). Patients with PTSD (vs. GAD/HC) demonstrated attenuated alpha power in the visual cortex and key hubs of the DMN (posterior cingulate cortex/PCC and medial prefrontal cortex/mPFC) at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs. S-RS), patients with PTSD further demonstrated reduced alpha-frequency directed connectivity within the DMN (PCC→mPFC) and, importantly, from the visual cortex (VC) to both DMN hubs (VC→PCC and VC→mPFC), linking alpha deficits in the two systems. These interrelated alpha deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The identification of visual-cortex-DMN alpha dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations. SIGNIFICANCE STATEMENT Alpha (8-12 Hz) oscillations and the default mode network (DMN) both dominate the resting-state brain activity and are found to be closely related. In addition, aberrant alpha and DMN activities are both implicated in the pathophysiology of posttraumatic stress disorder (PTSD). Linking alpha and DMN aberrations in PTSD, our high-density EEG source analysis reveals that PTSD is associated with alpha power deficits across the DMN and visual cortex (VC) and deficient alpha-frequency connectivity from the VC to the DMN. That this visual-cortex-DMN alpha dysrhythmia further underpins hypervigilance symptoms in PTSD highlights a temporal-spatial network pathology, promoting network-based neural oscillatory interventions.

Growing evidence of transcranial alternating current stimulation (tACS) modulating intrinsic neural oscillations has spawned interest in applying tACS to treat psychiatric disorders associated with aberrant neural oscillations. The alpha rhythmic activity is known to dominate neural oscillations at the awake, restful state, while attenuated resting-state alpha activity has been implicated in anxious mood. Administering repeated alpha-frequency tACS (α-tACS; at individual peak alpha frequency; 8–12 Hz) over four consecutive days (in the experiment group, sham stimulation in the control group), we demonstrated immediate and lasting (>24 h) increases in resting-state posterior ➔frontal connectivity in the alpha frequency, quantified by Granger causality. Critically, this connectivity enhancement was accompanied by sustained reductions in both anxious arousal and negative perception of sensory stimuli. Resting-state alpha power also increased, albeit only transiently, reversing to the baseline level within 24 h after tACS. Therefore, the lasting enhancement of long-range alpha connectivity due to α-tACS differs from local alpha activity that is nonetheless conserved, highlighting the adaptability of alpha oscillatory networks. In light of increasing recognition of large-scale network dysfunctions as a transdiagnostic pathophysiology of psychiatric disorders, this enduring connectivity plasticity, along with the behavioral improvements, paves the way for tACS applications in clinical interventions of psychiatric ‘oscillopathies’.

Social anxiety is associated with biased social perception, especially of ambiguous cues. While aberrations in high-level processes (e.g., cognitive appraisal and interpretation) have been implicated in such biases, contributions of early, low-level stimulus processing remain unclear. Categorical perception represents an efficient process to resolve signal ambiguity, and categorical emotion perception can swiftly classify sensory input, “tagging” biologically important stimuli at early stages of processing to facilitate ecological response. However, early threat categorization could be disrupted by exaggerated (or disinhibited) threat processing in anxiety, resulting in biased perception of ambiguous signals. We tested this hypothesis among individuals with low and high trait social anxiety (LSA/HSA; defined relative to the current sample), who performed a 2-alternative-forced-choice (fear or neutral) task on facial expressions parametrically varied along a neutral-fear continuum. The groups diverged in the reaction time (RT) profile along the neutral-fear continuum, which was characteristic of categorical perception in the LSA (vs. HSA) group with drastically increased RT from neutral to intermediate (boundary) fear intensities, contrasting monotonic, non significant RT changes in the HSA group. Neurometric analysis along the continuum identified an early neutral-fear categorization operation (arising in the P1, an early visual event-related potential/ERP at 100 ms), which was nonetheless impaired in the HSA group (due to disinhibited response at the neutral-fear boundary). Absent group differences in higher-level cognitive operations (identified by later ERPs), current findings highlight a dispositional cognitive vulnerability in early visual categorization of social threat, which could precipitate further cognitive aberrations and, eventually, the onset of social anxiety disorder.

Distress intolerance (DI), a trait-like individual difference reflective of the inability to endure aversive affective states, is relevant to multiple forms of psychopathology, but its relations to theoretically-relevant neurobiological systems has received little attention. Altered response inhibition-related neurobiology has been theorized to underlie individual differences in DI, but little empirical work has been conducted. To test this hypothesis, baseline data from a large clinical sample with elevated risk for affective psychopathology was utilized (N = 254). Participants completed a complex Go/No-go task while EEG was recorded, and No-go N2/P3 amplitudes and latencies were measured. Based upon prior findings on the relations between these components and response inhibition, we hypothesized that DI would predict reduced No-go N2/P3 amplitude and greater No-go N2/P3 latency while controlling for current anxious/depressive symptom severity. Partially consistent with predictions, high DI was independently associated with reduced No-go N2 amplitude but was non-significantly related to latency, though high DI was linked with greater Go N2 latency. Contrary to predictions, no relations between DI and the P3 were found. Further, exploratory analyses revealed positive associations between DI and No-go P2 amplitude/latency. Correlations between components and task performance suggest that observed relations between DI and the P2/N2 may reflect inefficient rather than impaired response inhibition. Overall, results support the theorized relevance of response inhibition-linked neurobiology to individual differences in tolerance of distress over and above distress severity itself, and suggest specific relations between DI and alterations in early selective attention/conflict-monitoring but not evaluative phases of response inhibition.

Background Anomalies in default mode network (DMN) activity and alpha (8-12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that alpha oscillations support DMN functioning via inter-regional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of alpha deficits in the visual-cortex-DMN system in PTSD. Methods Patients with PTSD (N = 25) and two control groups—patients with Generalized Anxiety Disorder (N = 24) and healthy controls (N = 20)—underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical alpha activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA). Results Patients with PTSD (vs. controls) demonstrated attenuated alpha power in the visual cortex and key hubs of the DMN (posterior cingulate cortex/PCC and medial prefrontal cortex/mPFC) at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs. S-RS), patients with PTSD further demonstrated reduced alpha-frequency directed connectivity within the DMN (PCC→mPFC) and, importantly, from the visual cortex (VC) to both DMN hubs (VC→PCC and VC→mPFC), linking alpha deficits in the two systems. Conclusions These interrelated alpha deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The identification of visual-cortex-DMN alpha dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations.

BackgroundAnomalies in default mode network (DMN) activity and alpha (8-12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that alpha oscillations support DMN functioning via inter-regional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of alpha deficits in the visual-cortex-DMN system in PTSD.MethodsPatients with PTSD (N = 25) and two control groups—patients with Generalized Anxiety Disorder (N = 24) and healthy controls (N = 20)—underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical alpha activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA).ResultsPatients with PTSD (vs. controls) demonstrated attenuated alpha power in the visual cortex and key hubs of the DMN (posterior cingulate cortex/PCC and medial prefrontal cortex/mPFC) at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs. S-RS), patients with PTSD further demonstrated reduced alpha-frequency directed connectivity within the DMN (PCC→mPFC) and, importantly, from the visual cortex (VC) to both DMN hubs (VC→PCC and VC→mPFC), linking alpha deficits in the two systems.ConclusionsThese interrelated alpha deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The identification of visual-cortex-DMN alpha dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations.

Biological engineers often find it useful to communicate using diagrams. These diagrams can include information both about the structure of the nucleic acid sequences they are engineering and about the functional relationships between features of these sequences and/or other molecular species. A number of conventions and practices have begun to emerge within synthetic biology for creating such diagrams, and the Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard to organize, systematize, and extend such conventions in order to produce a coherent visual language. Here, we describe SBOL Visual version 2, which expands previous diagram standards to include new functional interactions, categories of molecular species, support for families of glyph variants, and the ability to indicate modular structure and mappings between elements of a system. SBOL Visual 2 also clarifies a number of requirements and best practices, significantly expands the collection of glyphs available to describe genetic features, and can be readily applied using a wide variety of software tools, both general and bespoke.

Social anxiety is associated with biased social perception, especially of ambiguous cues. While aberrations in high-level processes, including cognitive appraisal and interpretation of social signals, have been implicated in such biases, contributions of early, low-level stimulus processing remain unclear. Categorical perception is known to be an efficient process to resolve signal ambiguity, and categorical emotion perception can swiftly classify sensory input, “tagging” biologically important stimuli at early stages of processing to facilitate ecological response. However, early threat categorization could be disrupted by exaggerated threat processing in anxiety, resulting in biased perception of ambiguous signals. We tested this hypothesis among individuals with low and high trait social anxiety (LSA and HSA), who performed a 2-alternative-forced-choice (fear or neutral) task on facial expressions parametrically varied along a neutral-fear continuum. Clear divergence between the groups emerged in the profiles of reaction time (RT) and early visual response along the neutral-fear continuum. The LSA group exhibited a RT profile characteristic of categorical perception with drastically increased RT from neutral to intermediate (boundary) fear intensities, contrasting monotonous, non-significant RT changes in the HSA group. Neurometric analysis along the continuum identified an early fear-neutral categorization operation (arising in the P1, an early visual event-related potential/ERP at 100 ms) in the LSA (but not HSA) group. Absent group differences in higher-level cognitive operations (identified by later ERPs), current findings highlight a dispositional cognitive vulnerability in early visual categorization of social threat, which could precipitate further cognitive aberrations and, eventually, the onset of social anxiety disorder.

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems is to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.3.0 of SBOL, which builds upon version 2.2.0 published in last year’s JIB Standards in Systems Biology special issue. In particular, SBOL 2.3.0 includes means of succinctly representing sequence modifications, such as insertion, deletion, and replacement, an extension to support organization and attachment of experimental data derived from designs, and an extension for describing numerical parameters of design elements. The new version also includes specifying types of synthetic biology activities, unambiguous locations for sequences with multiple encodings, refinement of a number of validation rules, improved figures and examples, and clarification on a number of issues related to the use of external ontology terms.

Intrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder (PTSD). In contrast to abstract, verbal intrusions in other affective disorders, intrusive re-experiencing in PTSD is characterized by vivid sensory details as “flashbacks”. While prevailing PTSD models largely focus on dysregulated emotional processes, we hypothesize that deficient sensory inhibition in PTSD could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions of trauma. In 86 combat veterans, we examined resting-state alpha (8-12 Hz) oscillatory activity (in both power and posterior→frontal connectivity), given its key role in sensory cortical inhibition, in association with intrusive re-experiencing symptoms. A subset (N = 35) of veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed a strong association between intrusive re-experiencing symptoms and attenuated resting-state posterior→frontal alpha connectivity, which were both correlated with olfactory trauma memory (but not emotional response). Importantly, olfactory trauma memory was further identified as a full mediator of the relationship between alpha connectivity and intrusive re-experiencing in these veterans, suggesting that deficits in intrinsic sensory inhibition can contribute to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and spontaneously activating sensory representations of trauma, impaired sensory inhibition can constitute a sensory mechanism of intrusive re-experiencing in PTSD.HIGHLIGHTSAlpha oscillations (indexing sensory inhibition) measured in 86 combat veteransRe-experiencing symptom severity was associated with attenuated alpha connectivityTrauma memory for, not emotional response to, odors mediated this relationshipTrauma memories may arise via disinhibited activation of sensory representationsSensory systems may be novel target for intrusive re-experiencing symptom treatment

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.1 of SBOL that builds upon version 2.0 published in last year's JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements., Journal of Integrative Bioinformatics - JIB

The Synthetic Biology Open Language (SBOL) is a standard that enables collaborative engineering of biological systems across different institutions and tools. SBOL is developed through careful consideration of recent synthetic biology trends, real use cases, and consensus among leading researchers in the field and members of commercial biotechnology enterprises. We demonstrate and discuss how a set of SBOL-enabled software tools can form an integrated, cross-organizational workflow to recapitulate the design of one of the largest published genetic circuits to date, a 4-input AND sensor. This design encompasses the structural components of the system, such as its DNA, RNA, small molecules, and proteins, as well as the interactions between these components that determine the system's behavior/function. The demonstrated workflow and resulting circuit design illustrate the utility of SBOL 2.0 in automating the exchange of structural and functional specifications for genetic parts, devices, and the biological systems in which they operate.

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.2.0 of SBOL that builds upon version 2.1.0 published in last year’s JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

People who engineer biological organisms often find it useful to draw diagrams in order to communicate both the structure of the nucleic acid sequences that they are engineering and the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. SBOL Visual aims to organize and systematize such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 3.0 of SBOL Visual, a new major revision of the standard. The major difference between SBOL Visual 3 and SBOL Visual 2 is that diagrams and glyphs are defined with respect to the SBOL 3 data model rather than the SBOL 2 data model. A byproduct of this change is that the use of dashed undirected lines for subsystem mappings has been removed, pending future determination on how to represent general SBOL 3 constraints; in the interim, this annotation can still be used as an annotation. Finally, deprecated material has been removed from collection of glyphs: the deprecated "insulator" glyph and "macromolecule" alternative glyphs have been removed, as have the deprecated BioPAX alternatives to SBO terms.

Although transcranial alternating current stimulation (tACS) has demonstrated short-term effects in modulating neural oscillations, potential clinical efficacy of tACS for treating “oscillopathies” (disorders associated with aberrant neural oscillations) hinges on its ability to generate long-term neural plasticity, which can translate into lasting behavioral changes. Administering alpha-frequency tACS over 4 consecutive days, we evaluated short- and long-term (> 24 hours) effects of α-tACS on local alpha power and oscillatory connectivity, along with behavioral outcomes in anxious arousal and affective sensory perception. The α-tACS (vs. sham stimulation) group exhibited increases in posterior alpha power immediately and 30 minutes post-stimulation but not 24 hours post-stimulation, suggesting transient effects on local neuronal synchrony. Strikingly, long-range alpha-frequency Granger causal connectivity (posterior→frontal) increased not only immediately and 30 minutes but also 24 hours post-stimulation, paralleled by sustained reductions in anxious arousal and aversion to auditory stimuli. Therefore, tACS is capable of eliciting long-term plasticity in long-range oscillatory connectivity with direct, lasting behavioral consequences, while leaving endogenous local oscillations unaltered. This temporal disparity in local and network effects favors the view of large-scale network strengthening by tACS, calling for research attention to the circuit and network impacts of tACS. Critically, with the growing recognition of large-scale network dysfunctions as a transdiagnostic pathophysiology of psychiatric disorders, this connectivity plasticity advocates for the clinical application of tACS with its unique advantage in tackling network pathologies.

The role of the sensory cortex, beyond the amygdala, has been increasingly recognized in animal associative learning and memory. Here, we examined olfactory cortical plasticity in human olfactory associative learning and memory, while elucidating related changes in emotional and perceptual responses. Psychophysical and neurometric analyses were conducted across an odor-morphing continuum, with the two extreme levels differentially conditioned with aversive and neutral stimuli. Conditioned odors acquired distinct emotional values, tracked by ensemble response patterns in the orbitofrontal (high-level) olfactory cortex. Also observed were enhanced perceptual discrimination and divergent ensemble neuronal response patterns in the anterior and posterior piriform (low-to-intermediate-level) olfactory cortices. Whereas emotional-learning-related changes, both behavioral and neural, maintained 8 days later, perceptual-learning-related changes, also both behavioral and neural, recovered by then, highlighting the human aptitude of forming persistent emotional memory and related sensory cortical plasticity in contrast to transient perceptual alterations of sensory stimuli associated with mild aversive experiences.

Background Although a burgeoning line of research identifies emotion regulation difficulties as a potential maintenance factor for posttraumatic stress disorder (PTSD), little is known in regard to what emotion regulation strategies individuals with PTSD use in their daily lives, their predictors, and their consequences on later PTSD symptoms. Method The current study utilized ecological momentary assessment (EMA) design to explore prospective relationships between maladaptive and adaptive emotion regulation strategy use and PTSD symptoms in participants with PTSD (N = 30). Participants completed 4 EMAs per day over 8 days, assessing stressors, emotional response, and emotion regulation strategy use. Results Individuals with PTSD most commonly used avoidance as an emotion regulation strategy. Multilevel modeling indicated that baseline PTSD symptoms predicted maladaptive emotion regulation strategy use. After covarying for morning PTSD symptoms, maladaptive emotion regulation prospectively predicted increased PTSD symptoms later in the day. Adaptive emotion regulation strategies did not uniquely predict later PTSD symptoms. Conclusion In line with conceptualizations of difficulties in emotion regulation as a transdiagnostic maintenance factor in PTSD, findings indicate that maladaptive emotion regulation strategies in response to stressors exacerbate PTSD symptoms. The use of adaptive emotion regulation strategies had no positive or negative impact on subsequent PTSD symptoms. Limitations Future studies should utilize longer-term prospective designs.

Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >105 members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics.

The synthetic biology research community describes a standard language for exchanging designs of biological 'parts'. The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.

Large genetic engineering projects require more cistrons and consequently more strong and reliable transcriptional terminators. We have measured the strengths of a library of terminators, including 227 that are annotated in Escherichia coli--90 of which we also tested in the reverse orientation--and 265 synthetic terminators. Within this library we found 39 strong terminators, yielding50-fold reduction in downstream expression, that have sufficient sequence diversity to reduce homologous recombination when used together in a design. We used these data to determine how the terminator sequence contributes to its strength. The dominant parameters were incorporated into a biophysical model that considers the role of the hairpin in the displacement of the U-tract from the DNA. The availability of many terminators of varying strength, as well as an understanding of the sequence dependence of their properties, will extend their usability in the forward design of synthetic cistrons.

Post-traumatic stress disorder is characterized by exaggerated threat response, and theoretical accounts to date have focused on impaired threat processing and dysregulated prefrontal-cortex-amygdala circuitry. Nevertheless, evidence is accruing for broad, threat-neutral sensory hyperactivity in post-traumatic stress disorder. As low-level, sensory processing impacts higher-order operations, such sensory anomalies can contribute to widespread dysfunctions, presenting an additional aetiological mechanism for post-traumatic stress disorder. To elucidate a sensory pathology of post-traumatic stress disorder, we examined intrinsic visual cortical activity (based on posterior alpha oscillations) and bottom-up sensory-driven causal connectivity (Granger causality in the alpha band) during a resting state (eyes open) and a passive, serial picture viewing state. Compared to patients with generalized anxiety disorder (n = 24) and healthy control subjects (n = 20), patients with post-traumatic stress disorder (n = 25) demonstrated intrinsic sensory hyperactivity (suppressed posterior alpha power, source-localized to the visual cortex-cuneus and precuneus) and bottom-up inhibition deficits (reduced posterior→frontal Granger causality). As sensory input increased from resting to passive picture viewing, patients with post-traumatic stress disorder failed to demonstrate alpha adaptation, highlighting a rigid, set mode of sensory hyperactivity. Interestingly, patients with post-traumatic stress disorder also showed heightened frontal processing (augmented frontal gamma power, source-localized to the superior frontal gyrus and dorsal cingulate cortex), accompanied by attenuated top-down inhibition (reduced frontal→posterior causality). Importantly, not only did suppressed alpha power and bottom-up causality correlate with heightened frontal gamma power, they also correlated with increased severity of sensory and executive dysfunctions (i.e. hypervigilance and impulse control deficits, respectively). Therefore, sensory aberrations help construct a vicious cycle in post-traumatic stress disorder that is in action even at rest, implicating dysregulated triangular sensory-prefrontal-cortex-amygdala circuitry: intrinsic sensory hyperactivity and disinhibition give rise to frontal overload and disrupt executive control, fuelling and perpetuating post-traumatic stress disorder symptoms. Absent in generalized anxiety disorder, these aberrations highlight a unique sensory pathology of post-traumatic stress disorder (ruling out effects merely reflecting anxious hyperarousal), motivating new interventions targeting sensory processing and the sensory brain in these patients.

Synthetic Biology Open Language (SBOL) Visual is a graphical standard for genetic engineering. It consists of symbols representing DNA subsequences, including regulatory elements and DNA assembly features. These symbols can be used to draw illustrations for communication and instruction, and as image assets for computer-aided design. SBOL Visual is a community standard, freely available for personal, academic, and commercial use (Creative Commons CC0 license). We provide prototypical symbol images that have been used in scientific publications and software tools. We encourage users to use and modify them freely, and to join the SBOL Visual community: http://www.sbolstandard.org/visual., This Community Page introduces SBOL Visual—a standard visual language for DNA design and synthetic biology. Researchers are encouraged to download the symbols, use them freely, and suggest additions.

The Synthetic Biology Open Language (SBOL) is an emerging data standard for representing synthetic biology designs. The goal of SBOL is to improve the reproducibility of these designs and their electronic exchange between researchers and/or genetic design automation tools. The latest version of the standard, SBOL 2.0, enables the annotation of a large variety of biological components (e.g., DNA, RNA, proteins, complexes, small molecules, etc.) and their interactions. SBOL 2.0 also allows researchers to organize components into hierarchical modules, to specify their intended functions, and to link modules to models that describe their behavior mathematically. To support the use of SBOL 2.0, we have developed the libSBOLj 2.0 Java library, which provides an easy to use Application Programming Interface (API) for developers, including manipulation of SBOL constructs, serialization to and from an RDF/XML file format, and migration support in the form of conversion from the prior SBOL 1.1 standard to SBOL 2.0. This letter describes the libSBOLj 2.0 library and key engineering decisions involved in its design.

One of the visions of synthetic biology is to be able to program cells using a language that is similar to that used to program computers or robotics. For large genetic programs, keeping track of the DNA on the level of nucleotides becomes tedious and error prone, requiring a new generation of computer-aided design (CAD) software. To push the size of projects, it is important to abstract the designer from the process of part selection and optimization. The vision is to specify genetic programs in a higher-level language, which a genetic compiler could automatically convert into a DNA sequence. Steps towards this goal include: defining the semantics of the higher-level language, algorithms to select and assemble parts, and biophysical methods to link DNA sequence to function. These will be coupled to graphic design interfaces and simulation packages to aid in the prediction of program dynamics, optimize genes, and scan projects for errors.

Summary Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.0 of SBOL, introducing a standardized format for the electronic exchange of information on the structural and functional aspects of biological designs. The standard has been designed to support the explicit and unambiguous description of biological designs by means of a well defined data model. The standard also includes rules and best practices on how to use this data model and populate it with relevant design details. The publication of this specification is intended to make these capabilities more widely accessible to potential developers and users in the synthetic biology community and beyond.

Since the discovery of restriction enzymes and the generation of the first recombinant DNA molecule over 40 years ago, molecular biology has evolved into a multidisciplinary field that has democratized the conversion of a digitized DNA sequence stored in a computer into its biological counterpart, usually as a plasmid, stored in a living cell. In this article, we summarize the most relevant tools that allow the swift assembly of DNA sequences into useful plasmids for biotechnological purposes. We cover the main components and stages in a typical DNA assembly workflow, namely in silico design, de novo gene synthesis, and in vitro and in vivo sequence assembly methodologies.

The design and construction of engineered organisms is an emerging new discipline called synthetic biology and holds considerable promise as a new technological platform. The design of biologically engineered systems is however nontrivial, requiring contributions from a wide array of disciplines. One particular issue that confronts synthetic biologists is the ability to unambiguously describe novel designs such that they can be reengineered by a third-party. For this reason, the synthetic biology open language (SBOL) was developed as a community wide standard for formally representing biological designs. A design created by one engineering team can be transmitted electronically to another who can then use this design to reproduce the experimental results. The development and the community of the SBOL standard started in 2008 and has since grown in use with now over 80 participants, including international, academic, and industrial interests. SBOL has stimulated the development of repositories and software tools to help synthetic biologists in their design efforts. This chapter summarizes the latest developments and future of the SBOL standard and its supporting infrastructure.

The design and construction of engineered organisms is an emerging new discipline called synthetic biology and holds considerable promise as a new technological platform. The design of biologically engineered systems is however nontrivial, requiring contributions from a wide array of disciplines. One particular issue that confronts synthetic biologists is the ability to unambiguously describe novel designs such that they can be reengineered by a third-party. For this reason, the synthetic biology open language (SBOL) was developed as a community wide standard for formally representing biological designs. A design created by one engineering team can be transmitted electronically to another who can then use this design to reproduce the experimental results. The development and the community of the SBOL standard started in 2008 and has since grown in use with now over 80 participants, including international, academic, and industrial interests. SBOL has stimulated the development of repositories and software tools to help synthetic biologists in their design efforts. This chapter summarizes the latest developments and future of the SBOL standard and its supporting infrastructure.

While the first version of the Synthetic Biology Open Language (SBOL) has been adopted by several academic and commercial genetic design automation (GDA) software tools, it only covers a limited number of the requirements for a standardized exchange format for synthetic biology. In particular, SBOL Version 1.1 is capable of representing DNA components and their hierarchical composition via sequence annotations. This proposal revises SBOL Version 1.1, enabling the representation of a wider range of components with and without sequences, including RNA components, protein components, small molecules, and molecular complexes. It also introduces modules to instantiate groups of components on the basis of their shared function and assert molecular interactions between components. By increasing the range of structural and functional descriptions in SBOL and allowing for their composition, the proposed improvements enable SBOL to represent and facilitate the exchange of a broader class of genetic designs.

Genetic circuits perform computational operations based on interactions between freely diffusing molecules within a cell. When transcription factors are combined to build a circuit, unintended interactions can disrupt its function. Here, we apply 'part mining' to build a library of 73 TetR-family repressors gleaned from prokaryotic genomes. The operators of a subset were determined using an in vitro method, and this information was used to build synthetic promoters. The promoters and repressors were screened for cross-reactions. Of these, 16 were identified that both strongly repress their cognate promoter (5- to 207-fold) and exhibit minimal interactions with other promoters. Each repressor-promoter pair was converted to a NOT gate and characterized. Used as a set of 16 NOT/NOR gates, there are >10[superscript 54] circuits that could be built by changing the pattern of input and output promoters. This represents a large set of compatible gates that can be used to construct user-defined circuits., United States. Air Force Office of Scientific Research (Award FA9550-11-C-0028), American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship (32 CFR 168a), United States. Defense Advanced Research Projects Agency. Chronical of Lineage Indicative of Origins (N66001-12-C-4016), United States. Office of Naval Research (N00014-13-1-0074), National Institutes of Health (U.S.) (GM095765), National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (SA5284-11210)