ASU Scholarship Showcase

Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites.

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms.

One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.

Humans are able to modulate digit forces as a function of position despite changes in digit placement that might occur from trial to trial or when changing grip type for object manipulation. Although this phenomenon is likely to rely on sensing the position of the digits relative to each other and the object, the underlying mechanisms remain unclear. To address this question, we asked subjects (n = 30) to match perceived vertical distance between the center of pressure (CoP) of the thumb and index finger pads (d_y) of the right hand (“reference” hand) using the same hand (“test” hand). The digits of reference hand were passively placed collinearly (d_y = 0 mm). Subjects were then asked to exert different combinations of normal and tangential digit forces (F_n and F_tan, respectively) using the reference hand and then match the memorized d_y using the test hand. The reference hand exerted F_tan of thumb and index finger in either same or opposite direction. We hypothesized that, when the tangential forces of the digits are produced in opposite directions, matching error (1) would be biased toward the directions of the tangential forces; and (2) would be greater when the remembered relative contact points are matched with negligible digit force production. For the test hand, digit forces were either negligible (0.5–1 N, 0 ± 0.25 N; Experiment 1) or the same as those exerted by the reference hand (Experiment 2).Matching error was biased towards the direction of digit tangential forces: thumb CoP was placed higher than the index finger CoP when thumb and index finger F_tan were directed upward and downward, respectively, and vice versa (p < 0.001). However, matching error was not dependent on whether the reference and test hand exerted similar or different forces. We propose that the expected sensory consequence of motor commands for tangential forces in opposite directions overrides estimation of fingertip position through haptic sensory feedback.

Recent studies about sensorimotor control of the human hand have focused on how dexterous manipulation is learned and generalized. Here we address this question by testing the extent to which learned manipulation can be transferred when the contralateral hand is used and/or object orientation is reversed. We asked subjects to use a precision grip to lift a grip device with an asymmetrical mass distribution while minimizing object roll during lifting by generating a compensatory torque. Subjects were allowed to grasp anywhere on the object’s vertical surfaces, and were therefore able to modulate both digit positions and forces. After every block of eight trials performed in one manipulation context (i.e., using the right hand and at a given object orientation), subjects had to lift the same object in the second context for one trial (transfer trial).

Context changes were made by asking subjects to switch the hand used to lift the object and/or rotate the object 180° about a vertical axis. Therefore, three transfer conditions, hand switch (HS), object rotation (OR), and both hand switch and object rotation (HS+OR), were tested and compared with hand matched control groups who did not experience context changes. We found that subjects in all transfer conditions adapted digit positions across multiple transfer trials similar to the learning of control groups, regardless of different changes of contexts. Moreover, subjects in both HS and HS+OR group also adapted digit forces similar to the control group, suggesting independent learning of the left hand. In contrast, the OR group showed significant negative transfer of the compensatory torque due to an inability to adapt digit forces. Our results indicate that internal representations of dexterous manipulation tasks may be primarily built through the hand used for learning and cannot be transferred across hands.

Sensorimotor control theories propose that the central nervous system exploits expected sensory consequences generated by motor commands for movement planning, as well as online sensory feedback for comparison with expected sensory feedback for monitoring and correcting, if needed, ongoing motor output. In our study, we tested this theoretical framework by quantifying the functional role of expected vs. actual proprioceptive feedback for planning and regulation of gait in humans. We addressed this question by using a novel methodological approach to deliver fast perturbations of the walking surface stiffness, in conjunction with a virtual reality system that provided visual feedback of upcoming changes of surface stiffness. In the “predictable” experimental condition, we asked subjects to learn associating visual feedback of changes in floor stiffness (sand patch) during locomotion to quantify kinematic and kinetic changes in gait prior to and during the gait cycle. In the “unpredictable” experimental condition, we perturbed floor stiffness at unpredictable instances during the gait to characterize the gait-phase dependent strategies in recovering the locomotor cycle. For the “unpredictable” conditions, visual feedback of changes in floor stiffness was absent or inconsistent with tactile and proprioceptive feedback. The investigation of these perturbation-induced effects on contralateral leg kinematics revealed that visual feedback of upcoming changes in floor stiffness allows for both early (preparatory) and late (post-perturbation) changes in leg kinematics. However, when proprioceptive feedback is not available, the early responses in leg kinematics do not occur while the late responses are preserved although in a, slightly attenuated form. The methods proposed in this study and the preliminary results of the kinematic response of the contralateral leg open new directions for the investigation of the relative role of visual, tactile, and proprioceptive feedback on gait control, with potential implications for designing novel robot-assisted gait rehabilitation approaches.

Cyanobacteria are considered good models for biohydrogen production because they are relatively simple organisms with a demonstrable ability to generate H₂ under certain physiological conditions. However, most produce only little H₂, revert readily to H₂ consumption, and suffer from hydrogenase sensitivity to O₂. Strains of the cyanobacteria Lyngbya aestuarii and Microcoleus chthonoplastes obtained from marine intertidal cyanobacterial mats were recently found to display much better H₂ production potential. Because of their ecological origin in environments that become quickly anoxic in the dark, we hypothesized that this differential ability may have evolved to serve a role in the fermentation of the photosynthate. Here we show that, when forced to ferment internal substrate, these cyanobacteria display desirable characteristics of physiological H₂ production. Among them, the strain L. aestuarii BL J had the fastest specific rates and attained the highest H₂ concentrations during fermentation of photosynthate, which proceeded via a mixed acid fermentation pathway to yield acetate, ethanol, lactate, H₂, CO₂, and pyruvate. Contrary to expectations, the H₂ yield per mole of glucose was only average compared to that of other cyanobacteria. Thermodynamic analyses point to the use of electron donors more electronegative than NAD(P)H in Lyngbya hydrogenases as the basis for its strong H₂ production ability. In any event, the high specific rates and H₂ concentrations coupled with the lack of reversibility of the enzyme, at the expense of internal, photosynthetically generated reductants, makes L. aestuarii BL J and/or its enzymes, a potentially feasible platform for large-scale H₂ production.

The intact nervous system has an exquisite ability to modulate the activity of multiple muscles acting at one or more joints to produce an enormous range of actions. Seemingly simple tasks, such as reaching for an object or walking, in fact rely on very complex spatial and temporal patterns of muscle activations. Neurological disorders such as stroke and focal dystonia affect the ability to coordinate multi-joint movements. This article reviews the state of the art of research of muscle synergies in the intact and damaged nervous system, their implications for recovery and rehabilitation, and proposes avenues for research aimed at restoring the nervous system’s ability to control movement.

Dehalococcoides mccartyi strains are of particular importance for bioremediation due to their unique capability of transforming perchloroethene (PCE) and trichloroethene (TCE) to non-toxic ethene, through the intermediates cis-dichloroethene (cis-DCE) and vinyl chloride (VC). Despite the widespread environmental distribution of Dehalococcoides, biostimulation sometimes fails to promote dechlorination beyond cis-DCE. In our study, microcosms established with garden soil and mangrove sediment also stalled at cis-DCE, albeit Dehalococcoides mccartyi containing the reductive dehalogenase genes tceA, vcrA and bvcA were detected in the soil/sediment inocula. Reductive dechlorination was not promoted beyond cis-DCE, even after multiple biostimulation events with fermentable substrates and a lengthy incubation.

However, transfers from microcosms stalled at cis-DCE yielded dechlorination to ethene with subsequent enrichment cultures containing up to 10⁹ Dehalococcoides mccartyi cells mL^-1. Proteobacterial classes which dominated the soil/sediment communities became undetectable in the enrichments, and methanogenic activity drastically decreased after the transfers. We hypothesized that biostimulation of Dehalococcoides in the cis-DCE-stalled microcosms was impeded by other microbes present at higher abundances than Dehalococcoides and utilizing terminal electron acceptors from the soil/sediment, hence, outcompeting Dehalococcoides for H₂. In support of this hypothesis, we show that garden soil and mangrove sediment microcosms bioaugmented with their respective cultures containing Dehalococcoides in high abundance were able to compete for H² for reductive dechlorination from one biostimulation event and produced ethene with no obvious stall. Overall, our results provide an alternate explanation to consolidate conflicting observations on the ubiquity of Dehalococcoides mccartyi and occasional stalling of dechlorination at cis-DCE; thus, bringing a new perspective to better assess biological potential of different environments and to understand microbial interactions governing bioremediation.

Studies have shown that internal representations of manipulations of objects with asymmetric mass distributions that are generated within a specific orientation are not generalizable to novel orientations, i.e., subjects fail to prevent object roll on their first grasp-lift attempt of the object following 180° object rotation. This suggests that representations of these manipulations are specific to the reference frame in which they are formed. However, it is unknown whether that reference frame is specific to the hand, the body, or both, because rotating the object 180° modifies the relation between object and body as well as object and hand. An alternative, untested explanation for the above failure to generalize learned manipulations is that any rotation will disrupt grasp performance, regardless if the reference frame in which the manipulation was learned is maintained or modified. We examined the effect of rotations that (1) maintain and (2) modify relations between object and body, and object and hand, on the generalizability of learned two-digit manipulation of an object with an asymmetric mass distribution. Following rotations that maintained the relation between object and body and object and hand (e.g., rotating the object and subject 180°), subjects continued to use appropriate digit placement and load force distributions, thus generating sufficient compensatory moments to minimize object roll. In contrast, following rotations that modified the relation between (1) object and hand (e.g. rotating the hand around to the opposite object side), (2) object and body (e.g. rotating subject and hand 180°), or (3) both (e.g. rotating the subject 180°), subjects used the same, yet inappropriate digit placement and load force distribution, as those used prior to the rotation. Consequently, the compensatory moments were insufficient to prevent large object rolls. These findings suggest that representations of learned manipulation of objects with asymmetric mass distributions are specific to the body- and hand-reference frames in which they were learned.

Background: Buffering to achieve pH control is crucial for successful trichloroethene (TCE) anaerobic bioremediation. Bicarbonate (HCO3−) is the natural buffer in groundwater and the buffer of choice in the laboratory and at contaminated sites undergoing biological treatment with organohalide respiring microorganisms. However, HCO3− also serves as the electron acceptor for hydrogenotrophic methanogens and hydrogenotrophic homoacetogens, two microbial groups competing with organohalide respirers for hydrogen (H2). We studied the effect of HCO3− as a buffering agent and the effect of HCO3−-consuming reactions in a range of concentrations (2.5-30 mM) with an initial pH of 7.5 in H2-fed TCE reductively dechlorinating communities containing Dehalococcoides, hydrogenotrophic methanogens, and hydrogenotrophic homoacetogens.

Results: Rate differences in TCE dechlorination were observed as a result of added varying HCO3− concentrations due to H2-fed electrons channeled towards methanogenesis and homoacetogenesis and pH increases (up to 8.7) from biological HCO3− consumption. Significantly faster dechlorination rates were noted at all HCO3− concentrations tested when the pH buffering was improved by providing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) as an additional buffer. Electron balances and quantitative PCR revealed that methanogenesis was the main electron sink when the initial HCO3− concentrations were 2.5 and 5 mM, while homoacetogenesis was the dominant process and sink when 10 and 30 mM HCO3− were provided initially.

Conclusions: Our study reveals that HCO3− is an important variable for bioremediation of chloroethenes as it has a prominent role as an electron acceptor for methanogenesis and homoacetogenesis. It also illustrates the changes in rates and extent of reductive dechlorination resulting from the combined effect of electron donor competition stimulated by HCO3− and the changes in pH exerted by methanogens and homoacetogens.