Enhanced HONO Formation from Aqueous Nitrate Photochemistry in the Presence of Marine Relevant Organics: Impact of Marine-Dissolved Organic Matter (m-DOM) Concentration on HONO Yields and Potential Synergistic Effects of Compounds within m-DOM.

Nitrous acid (HONO) is a key molecule in the reactive nitrogen cycle. However, sources and sinks for HONO are not fully understood. Particulate nitrate photochemistry has been suggested to play a role in the formation of HONO in the marine boundary layer (MBL). Here we investigate the impact of marine relevant organic compounds on HONO formation from aqueous nitrate photochemistry. In particular, steady-state, gas-phase HONO yields were measured from irradiated nitrate solutions at low pH containing marine-dissolved organic matter (m-DOM). m-DOM induces a nonlinear increase in HONO yield across all concentrations compared to that for pure nitrate solutions, with rates of HONO formation increasing by up to 3-fold when m-DOM is present. Furthermore, to understand the potential synergistic effects that may occur within complex samples such as m-DOM, mixtures of chromophoric (light-absorbing) and aliphatic (non-light-absorbing) molecular proxies were utilized. In particular, mixtures of 4-benzoylbenzoic acid (4-BBA) and ethylene glycol (EG) in acidic aqueous solutions containing nitrate showed more HONO upon irradiation compared to solutions containing only one of the molecular proxies. This suggests that synergistic effects in the HONO formation can occur in complex organic samples. Atmospheric implications of the results presented here are discussed.

Characterization of the Statistical Signatures of Micro-Movements Underlying Natural Gait Patterns in Children with Phelan McDermid Syndrome: Towards Precision-Phenotyping of Behavior in ASD.

BACKGROUND: There is a critical need for precision phenotyping across neurodevelopmental disorders, especially in individuals who receive a clinical diagnosis of autism spectrum disorder (ASD). Phelan-McDermid deletion syndrome (PMS) is one such example, as it has a high penetrance of ASD. At present, no biometric characterization of the behavioral phenotype within PMS exists. METHODS: We introduce a data-type and statistical framework that permits the personalized profiling of naturalistic behaviors. Walking patterns were assessed in 30 participants (16 PMS, 3 idiopathic-ASD and 11 age- and sex-matched controls). Each individual's micro-movement signatures were recorded at 240 Hz. We empirically estimated the parameters of the continuous Gamma family of probability distributions and calculated their ranges. These estimated stochastic signatures were then mapped on the Gamma plane to obtain several statistical indexes for each child. To help visualize complex patterns across the cohort, we introduce new tools that enable the assessment of connectivity and modularity indexes across the peripheral network of rotational joints. RESULTS: Typical walking signatures are absent in all children with PMS as well as in the children with idiopathic-ASD (iASD). Underlying these patterns are atypical leg rotational acceleration signatures that render participants with PMS unstable with rotations that are much faster than controls. The median values of the estimated Gamma parameters serve as a cutoff to automatically separate children with PMS 5-7 years old from adolescents with PMS 12-16 years old, the former displaying more randomness and larger noise. The fluctuations in the arm's motions during the walking also have atypical statistics that separate males from females in PMS and show higher rates of noise accumulation in idiopathic ASD (iASD) children. Despite high heterogeneity, all iASD children have excess noise, a narrow range of probability-distribution shapes across the body joints and a distinct joint network connectivity pattern. Both PMS and iASD have systemic issues with noise in micro-motions across the body with specific signatures for each child that, as a cohort, selectively deviates from controls. CONCLUSIONS: We provide a new methodology for precision behavioral phenotyping with the potential to use micro-movement output noise as a natural classifier of neurodevelopmental disorders of known etiology. This approach may help us better understand idiopathic neurodevelopmental disorders and personalize the assessments of natural movements in these populations.

Schizophrenia: The micro-movements perspective.

Traditionally conceived of and studied as a disorder of cognitive and emotional functioning, schizophrenia (SZ) is also characterized by alterations in bodily sensations. These have included subjective reports based on self-evaluations and/or clinical observations describing motor, as well as sensory-based corporeal anomalies. There has been, however, a paucity of objective methods to capture and characterize bodily issues in SZ. Here we present a new research method and statistical platform that enables precise evaluation of peripheral activity and its putative contributions to the cognitive control of visuomotor actions. Specifically, we introduce new methods that facilitate the individualized characterization of the function of sensory-motor systems so as to detect if subjects perform outside of normal limits. In this paper, we report data from a cohort of patients with a clinical diagnosis of SZ. First, we characterize neurotypical subjects performing a visually guided pointing task that requires visuomotor transformations, multi-joint coordination, and the proper balance between different degrees of intent, among other factors. Then we measure SZ patients against the normative statistical ranges empirically determined. To this end, we examine the stochastic signatures of minute fluctuations in motor performance (micro-movements) of various velocity- and geometric-transformation-dependent trajectory parameters from the hand motions. These include the motions en-route to the target as well as spontaneous (without instructions) hand-retractions to rest. The comparisons reveal fundamental differences between SZ patients and controls. Specifically, velocity-dependent signatures show that SZ patients move significantly slower than controls with more noise and randomness in their moment-by-moment hand micro-motions. Furthermore, the normative geometric-dependent signatures of deliberateness are absent from the goal-directed reaches in SZ, but present within normative ranges in their spontaneous hand retractions to rest. Given that the continuous flow of micro-motions contributes to internally sensed feedback from self-produced movements, it is highly probable that sensory-motor integration with externally perceived inputs is impaired. Such impairments in this SZ cohort seem to specifically alter the balance between deliberate and spontaneous control of actions. We interpret these results as potential indexes of avolition and lack of agency and action ownership. We frame our results in the broad context of Precision Psychiatry initiatives and discuss possible implications on the putative contributions of the peripheral nervous system to the internal models for the cognitive control of self-produced actions in the individual with a clinical diagnosis of SZ.

Toward Precision Psychiatry: Statistical Platform for the Personalized Characterization of Natural Behaviors.

There is a critical need for new analytics to personalize behavioral data analysis across different fields, including kinesiology, sports science, and behavioral neuroscience. Specifically, to better translate and integrate basic research into patient care, we need to radically transform the methods by which we describe and interpret movement data. Here, we show that hidden in the "noise," smoothed out by averaging movement kinematics data, lies a wealth of information that selectively differentiates neurological and mental disorders such as Parkinson's disease, deafferentation, autism spectrum disorders, and schizophrenia from typically developing and typically aging controls. In this report, we quantify the continuous forward-and-back pointing movements of participants from a large heterogeneous cohort comprising typical and pathological cases. We empirically estimate the statistical parameters of the probability distributions for each individual in the cohort and report the parameter ranges for each clinical group after characterization of healthy developing and aging groups. We coin this newly proposed platform for individualized behavioral analyses "precision phenotyping" to distinguish it from the type of observational-behavioral phenotyping prevalent in clinical studies or from the "one-size-fits-all" model in basic movement science. We further propose the use of this platform as a unifying statistical framework to characterize brain disorders of known etiology in relation to idiopathic neurological disorders with similar phenotypic manifestations.

Automatically Characterizing Sensory-Motor Patterns Underlying Reach-to-Grasp Movements on a Physical Depth Inversion Illusion.

Recently, movement variability has been of great interest to motor control physiologists as it constitutes a physical, quantifiable form of sensory feedback to aid in planning, updating, and executing complex actions. In marked contrast, the psychological and psychiatric arenas mainly rely on verbal descriptions and interpretations of behavior via observation. Consequently, a large gap exists between the body's manifestations of mental states and their descriptions, creating a disembodied approach in the psychological and neural sciences: contributions of the peripheral nervous system to central control, executive functions, and decision-making processes are poorly understood. How do we shift from a psychological, theorizing approach to characterize complex behaviors more objectively? We introduce a novel, objective, statistical framework, and visuomotor control paradigm to help characterize the stochastic signatures of minute fluctuations in overt movements during a visuomotor task. We also quantify a new class of covert movements that spontaneously occur without instruction. These are largely beneath awareness, but inevitably present in all behaviors. The inclusion of these motions in our analyses introduces a new paradigm in sensory-motor integration. As it turns out, these movements, often overlooked as motor noise, contain valuable information that contributes to the emergence of different kinesthetic percepts. We apply these new methods to help better understand perception-action loops. To investigate how perceptual inputs affect reach behavior, we use a depth inversion illusion (DII): the same physical stimulus produces two distinct depth percepts that are nearly orthogonal, enabling a robust comparison of competing percepts. We find that the moment-by-moment empirically estimated motor output variability can inform us of the participants' perceptual states, detecting physiologically relevant signals from the peripheral nervous system that reveal internal mental states evoked by the bi-stable illusion. Our work proposes a new statistical platform to objectively separate changes in visual perception by quantifying the unfolding of movement, emphasizing the importance of including in the motion analyses all overt and covert aspects of motor behavior.

Methods to explore the influence of top-down visual processes on motor behavior.

Kinesthetic awareness is important to successfully navigate the environment. When we interact with our daily surroundings, some aspects of movement are deliberately planned, while others spontaneously occur below conscious awareness. The deliberate component of this dichotomy has been studied extensively in several contexts, while the spontaneous component remains largely under-explored. Moreover, how perceptual processes modulate these movement classes is still unclear. In particular, a currently debated issue is whether the visuomotor system is governed by the spatial percept produced by a visual illusion or whether it is not affected by the illusion and is governed instead by the veridical percept. Bistable percepts such as 3D depth inversion illusions (DIIs) provide an excellent context to study such interactions and balance, particularly when used in combination with reach-to-grasp movements. In this study, a methodology is developed that uses a DII to clarify the role of top-down processes on motor action, particularly exploring how reaches toward a target on a DII are affected in both deliberate and spontaneous movement domains.

UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph polarize F-actin during embryonic morphogenesis by regulating the WAVE/SCAR actin nucleation complex.

Many cells in a developing embryo, including neurons and their axons and growth cones, must integrate multiple guidance cues to undergo directed growth and migration. The UNC-6/netrin, SLT-1/slit, and VAB-2/Ephrin guidance cues, and their receptors, UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph, are known to be major regulators of cellular growth and migration. One important area of research is identifying the molecules that interpret this guidance information downstream of the guidance receptors to reorganize the actin cytoskeleton. However, how guidance cues regulate the actin cytoskeleton is not well understood. We report here that UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph differentially regulate the abundance and subcellular localization of the WAVE/SCAR actin nucleation complex and its activator, Rac1/CED-10, in the Caenorhabditis elegans embryonic epidermis. Loss of any of these three pathways results in embryos that fail embryonic morphogenesis. Similar defects in epidermal enclosure have been observed when CED-10/Rac1 or the WAVE/SCAR actin nucleation complex are missing during embryonic development in C. elegans. Genetic and molecular experiments demonstrate that in fact, these three axonal guidance proteins differentially regulate the levels and membrane enrichment of the WAVE/SCAR complex and its activator, Rac1/CED-10, in the epidermis. Live imaging of filamentous actin (F-actin) in embryos developing in the absence of individual guidance receptors shows that high levels of F-actin are not essential for polarized cell migrations, but that properly polarized distribution of F-actin is essential. These results suggest that proper membrane recruitment and activation of CED-10/Rac1 and of WAVE/SCAR by signals at the plasma membrane result in polarized F-actin that permits directed movements and suggest how multiple guidance cues can result in distinct changes in actin nucleation during morphogenesis.