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Cell type specialization is a hallmark of complex multicellular organisms and is usually established through implementation of cell-type-specific gene expression programs. The multicellular green algaVolvox carterihas just two cell types, germ and soma, that have previously been shown to have very different transcriptome compositions which match their specialized roles. Here we interrogated another potential mechanism for differentiation inV. carteri, cell type specific alternative transcript isoforms (CTSAI).

We used pre-existing predictions of alternative transcripts and de novo transcript assembly with HISAT2 and Ballgown software to compile a list of loci with two or more transcript isoforms, identified a small subset that were candidates for CTSAI, and manually curated this subset of genes to remove false positives. We experimentally verified three candidates using semi-quantitative RT-PCR to assess relative isoform abundance in each cell type.

Of the 1978 loci with two or more predicted transcript isoforms 67 of these also showed cell type isoform expression biases. After curation 15 strong candidates for CTSAI were identified, three of which were experimentally verified, and their predicted gene product functions were evaluated in light of potential cell type specific roles. A comparison of genes with predicted alternative splicing fromChlamydomonas reinhardtii, a unicellular relative ofV. carteri, identified little overlap between ortholog pairs with alternative splicing in both species. Finally, we interrogated cell type expression patterns of 126 V. carteripredicted RNA binding protein (RBP) encoding genes and found 40 that showed either somatic or germ cell expression bias. These RBPs are potential mediators of CTSAI inV. carteriand suggest possible pre-adaptation for cell type specific RNA processing and a potential path for generating CTSAI in the early ancestors of metazoans and plants.

We predicted numerous instances of alternative transcript isoforms in Volvox, only a small subset of which showed cell type specific isoform expression bias. However, the validated examples of CTSAI supported existing hypotheses about cell type specialization inV. carteri,and also suggested new hypotheses about mechanisms of functional specialization for their gene products. Our data imply that CTSAI operates as a minor but important component ofV. cartericellular differentiation and could be used as a model for how alternative isoforms emerge and co-evolve with cell type specialization.

 

Background: Cell type specialization is a hallmark of complex multicellular organisms and is usually established through implementation of cell-type-specific gene expression programs. The multicellular green alga Volvox carteri has just two cell types, germ and soma, that have previously been shown to have very different transcriptome com- positions which match their specialized roles. Here we interrogated another potential mechanism for differentiation in V. carteri, cell type specific alternative transcript isoforms (CTSAI). Methods: We used pre-existing predictions of alternative transcripts and de novo transcript assembly with HISAT2 and Ballgown software to compile a list of loci with two or more transcript isoforms, identified a small subset that were candidates for CTSAI, and manually curated this subset of genes to remove false positives. We experimentally verified three candidates using semi-quantitative RT-PCR to assess relative isoform abundance in each cell type. Results: Of the 1978 loci with two or more predicted transcript isoforms 67 of these also showed cell type isoform expression biases. After curation 15 strong candidates for CTSAI were identified, three of which were experimen- tally verified, and their predicted gene product functions were evaluated in light of potential cell type specific roles. A comparison of genes with predicted alternative splicing from Chlamydomonas reinhardtii, a unicellular relative of V. carteri, identified little overlap between ortholog pairs with alternative splicing in both species. Finally, we inter- rogated cell type expression patterns of 126 V. carteri predicted RBP encoding genes and found 40 that showed either somatic or germ cell expression bias. These RBPs are potential mediators of CTSAI in V. carteri and suggest possible pre-adaptation for cell type specific RNA processing and a potential path for generating CTSAI in the early ancestors of metazoans and plants. Conclusions: We predicted numerous instances of alternative transcript isoforms in Volvox, only a small subset of which showed cell type specific isoform expression bias. However, the validated examples of CTSAI supported existing hypotheses about cell type specialization in V. carteri, and also suggested new hypotheses about mecha- nisms of functional specialization for their gene products. Our data imply that CTSAI operates as a minor but impor- tant component of V. carteri cellular differentiation and could be used as a model for how alternative isoforms emerge and co-evolve with cell type specialization. 

Rotation manipulation tasks are a fundamental component of manipulation, however few benchmarks directly measure the limits of a hand's ability to rotate objects. This paper presents two benchmarks for quantitatively measuring the rotation manipulation capabilities of two-fingered hands. These benchmarks exists to augment the Asterisk Test to consider rotation manipulation ability. We propose two benchmarks: the first assesses a hand's limits to rotate objects clockwise and counterclockwise with minimal translation, and the second assesses how rotation manipulation impacts a hand's in-hand translation performance. We demonstrate the utility of these rotation benchmarks using three generic robot hand designs: 1) an asymmetrical two-linked versus one-linked gripper (2v1), 2) a symmetrical two-linked gripper (2v2), and 3) a symmetrical three-linked gripper (3v3). We conclude with a brief comparison between the hand designs and a observations about contact point selection for manipulation tasks, informed from our benchmark results. 

Adult acquired flatfoot deformity becomes permanent with stage III posterior tibialis tendon dysfunction and results in foot pain and difficulty walking and balancing. To prevent progression to stage III posterior tibialis tendon dysfunction when conservative treatment fails, a flexor digitorum longus to posterior tibialis tendon transfer is often conducted. However, since the flexor digitorum longus only has one-third the force-capability of the posterior tibialis, an osteotomy is typically also required. We propose the use of a novel implantable mechanism to replace the direct attachment of the tendon transfer with a sliding pulley to amplify the force transferred from the donor flexor digitorum longus to the foot arch. In this work, we created four OpenSim models of an arched foot, a flatfoot, a flatfoot with traditional tendon transfer, and a flatfoot with implant-modified tendon transfer. Paired with these models, we developed a forward dynamic simulation of the stance phase of gait that reproduces the medial/lateral distribution of vertical ground reaction forces. The simulation couples the use of a fixed tibia, moving ground plane methodology with simultaneous activation of nine extrinsic lower limb muscles. The arched foot and flatfoot models produced vertical ground reaction forces with the characteristic double-peak profile of gait, and the medial/lateral distribution of these forces compared well with the literature. The flatfoot model with implant-modified tendon transfer produced a 94.2% restoration of the medial/lateral distribution of vertical ground reaction forces generated by our arched foot model, which also represents a 2.1X improvement upon our tendon transfer model. This result demonstrates the feasibility of a pulley-like implant to improve functional outcomes for surgical treatment of adult acquired flatfoot deformity with ideal biomechanics in simulation. The real-world efficacy and feasibility of such a device will require further exploration of factors such as surgical variability, soft tissue interactions and healing response. 

Dynamic loading is a shared feature of tendon tissue homeostasis and pathology. Tendon cells have the inherent ability to sense mechanical loads that initiate molecular-level mechanotransduction pathways. While mature tendons require physiological mechanical loading in order to maintain and fine tune their extracellular matrix architecture, pathological loading initiates an inflammatory-mediated tissue repair pathway that may ultimately result in extracellular matrix dysregulation and tendon degeneration. The exact loading and inflammatory mechanisms involved in tendon healing and pathology is unclear although a precise understanding is imperative to improving therapeutic outcomes of tendon pathologies. Thus, various model systems have been designed to help elucidate the underlying mechanisms of tendon mechanobiology via mimicry of the in vivo tendon architecture and biomechanics. Recent development of model systems has focused on identifying mechanoresponses to various mechanical loading platforms. Less effort has been placed on identifying inflammatory pathways involved in tendon pathology etiology, though inflammation has been implicated in the onset of such chronic injuries. The focus of this work is to highlight the latest discoveries in tendon mechanobiology platforms and specifically identify the gaps for future work. An interdisciplinary approach is necessary to reveal the complex molecular interplay that leads to tendon pathologies and will ultimately identify potential regenerative therapeutic targets. 

We present a method for classifying the quality of near-contact grasps using spatial metrics that are recoverable from sensor data. Current methods often rely on calculating precise contact points, which are difficult to calculate in real life, or on tactile sensors or image data, which may be unavailable for some applications. Our method, in contrast, uses a mix of spatial metrics that do not depend on the fingers being in contact with the object, such as the object's approximate size and location. The grasp quality can be calculated {\em before} the fingers actually contact the object, enabling near-grasp quality prediction. Using a random forest classifier, the resulting system is able to predict grasp quality with 96\% accuracy using spatial metrics based on the locations of the robot palm, fingers and object. Furthermore, it can maintain an accuracy of 90\% when exposed to 10\% noise across all its inputs. 

Grasping a simple object from the side is easy-unless the object is almost as big as the hand or space constraints require positioning the robot hand awkwardly with respect to the object. We show that humans-when faced with this challenge-adopt coordinated finger movements which enable them to successfully grasp objects even from these awkward poses. We also show that it is relatively straight forward to implement these strategies autonomously. Our human-studies approach asks participants to perform grasping task by either "puppetteering" a robotic manipulator that is identical (geometrically and kinematically) to a popular underactuated robotic manipulator (the Barrett hand), or using sliders to control the original Barrett hand. Unlike previous studies, this enables us to directly capture and compare human manipulation strategies with robotic ones. Our observation is that, while humans employ underactuation, how they use it is fundamentally different (and more effective) than that found in existing hardware.