Biomedical Engineering and Bioengineering Commons^™

Son Is Essential For Nuclear Speckle Organization, Cell Cycle Progression And Pre-Mrna Splicing, Alok S. Sharma

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Nuclear speckles provide important spatial organization and dynamic regulation for pre-mRNA processing factors in mammalian cells. While the nuclear speckle proteome is complex, little is known at the molecular level about how these factors are organized into nuclear speckles or how alterations in the organization of these factors impacts gene expression. We have discovered a new function for a large (2564 amino acid) nuclear speckle protein called Son in maintaining the organization of pre-mRNA processing factors in nuclear speckles. Depletion of Son by RNAi causes snRNP and serine-arginine rich (SR protein) splicing factors to undergo dramatic disorganization into doughnut-shaped nuclear …

Predicting Vigilance Performance Under Transcranial Direct Current Stimulation, Nathaniel Reese Bridges

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A brain stimulation technology called transcranial direct current stimulation (tDCS) may potentially mitigate the vigilance decrement. To practically use such technology, however, a model is necessary that indicates vigilance performance, both when stimulation is being applied and not applied. To address this issue, the author developed models capable of predicting vigilance performance in real and control stimulation conditions using previous tDCS-study data. The "all possible combinations" regression method produced over 200 models, later screened to 10. The model with the best average %error (11.49 ± 0.10) used left hemispheric cerebral blood flow velocity (CBFVL) as its sole input term-accounting for …

Semi-Automated Dental Cast Analysis Software, Mathew Thomas

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Dental casts have been used extensively to study almost all aspects of the human dentition. These aspects varied from the study of tooth form and morphology, inheritance and genetics, growth and development, occlusion, arch alignment and crowding to mathematical determination of dental arch form.

The aim of this project was to develop a tool to semi-automate the measurement of dental casts that would be precise, accurate and efficient. Measurements include tooth widths, arch lengths and widths, angle of rotation and crown area for each tooth.

The task was divided into two different parts: first, the development of semi-automatic software to …

A Computational Tool For Biomolecular Structure Analysis Based On Chemical And Enzymatic Modification Of Native Proteins, Deacon John Sweeney

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Chemical and enzymatic modification of proteins is a well-established treatment technique for probing the conformational properties of these macromolecules. Investigators have recently extended the approach to probe many sites on a protein's structure in parallel manner, such that conformational properties of a target protein can be inferred. The modern approach uses mass spectrometry to quantify reactant loss and product formation. Rigorous analysis is challenging due to the high volume of mass spectrometric data that must be processed and interpreted.

An extensively interactive software suite has been developed to assist various aspects of the analytical protocol. The software offers a variety …

Cervical Spine Biomechanical Behavior And Injury, Mbulelo T. Makola

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A finite element model of the cervical spine including the C2 through C7 levels was developed in order to study the behavior of the cervical spine region. The model was validated in flexion extension, bending, and rotational load scenarios. The model was found to represent the biomechanical behavior of the cervical spine. The validated cervical spine finite element model was used to study spinal injury and disease processes. The model provided qualitative estimates of load carrying and stress distribution as well as range of motion.

The Molecular Basis Of The Interaction Between The Coxsackievirus And Adenovirus Receptor (Car) And Magi-1, Abimbola Olayinka Kolawole

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A major factor in virus entry into cells is localization and abundance of the primary receptor. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for group B coxsackievirus and many serotypes of adenovirus. In most epithelia, a seven exon isoform of CAR (CAR^Ex7) is exclusively localized at the basolateral surface where it behaves as a homophilic adhesion protein and is inaccessible for viral infection. However, in well-differentiated human airway epithelia, we recently discovered an alternatively spliced, low abundance isoform of CAR (CAR^Ex8) that is apically localized where it may initiate apical viral infection. The …

Tracking Of Bone Mass And Density During Childhood And Adolescence, Heidi J. Kalkwarf, Vicente Gilsanz, Joan M. Lappe, Sharon Oberfield, John A. Shepherd, Thomas N. Hangartner, Xangke Huang, Margaret M. Frederick, Karen K. Winer, Babette S. Zemel

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Context: Whether a child with low bone mineral density (BMD) at one point in time will continue to have low BMD, despite continued growth and maturation, is important clinically. The stability of a characteristic during growth is referred to as “tracking.”

Objective: We examined the degree of tracking in bone mineral content (BMC) and BMD during childhood and adolescence and investigated whether tracking varied according to age, sexual maturation, and changes in growth status.

Design: We conducted a longitudinal study with measurements at baseline and annually for 3 yr.

Setting: The Bone Mineral Density in Childhood Study was conducted at …

Height Adjustment In Assessing Dual Energy X-Ray Absorptiometry Measurements Of Bone Mass And Density In Children, Babette S. Zemel, Mary B. Leonard, Andrea Kelly, Joan M. Lappe, Vicente Gilsanz, Sharon Oberfield, Soroosh Mahboubi, John A. Shepherd, Thomas N. Hangartner, Margaret M. Frederick, Karen K. Winer, Heidi J. Kalkwarf

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Context: In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature.

Objective: The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children.

Design: Data from the Bone Mineral Density in Childhood Study (BMDCS) were used to develop adjustment methods that were validated using an independent cross-sectional sample of healthy children from the Reference Data Project (RDP).

Setting: We conducted the study in five …

Understanding The Molecular Dynamics Of Ypel3 And Fhit Gene Expression, Kevin Daniel Kelley

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A comprehensive understanding of the molecular signaling pathways that regulate cell growth and proliferation is essential in the realization of new therapeutic options to facilitate early detection and eradication of malignancy. Understanding the transcriptional regulation of the YPEL3 and FHIT genes forms the basis of this dissertation. YPEL3, or Yippee-like 3, is a newly identified p53 target gene that inhibits tumor cell growth and is thus itself, a novel tumor suppressor gene. FHIT, or Fragile histidine triad, is a well known tumor suppressor gene and is regulated at the transcriptional level by another growth inhibitory protein, FOXO3a, a Forkhead box …

A Biomechanical Comparison Of Locking Compression Plate Constructs With Plugs/Screws In Osteoporotic Bone Model, Krishna P. Desai

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Locking compression plates are proven to be safe for use in open reduction and internal fixation (ORIF) especially in osteoporotic bones. Because of various combinations of holes, the system provides more options for clinicians to use either locking screws or non-locking screws. This clinical research introduces screw like plugs which can be used along with the screws in case of locking compression plates. Experimental work was performed to determine the effectiveness of the plugs. The results showed that there is not a significant difference between the groups which used plugs and did not use the plugs, both in case of …

Extent And Effects Of Selection To Reduce Synthetic Cost Of Highly Expressed Proteins, Esley Marvin Heizer Jr

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Organisms that preferentially utilize less biosynthetically expensive amino acids in highly expressed genes exhibit metabolic efficiency. Exploration of this phenomenon has been limited to six prokaryotes.

I present a large scale analysis of metabolic efficiency in prokaryotic organisms and analysis of two eukaryotes (Saccharomyces cerevisiae and humans). Examination of 73 bacteria reveals the presence of metabolic efficiency in 66 organisms. The average correlation between amino acid biosynthetic cost and CAI scores in these organisms is -0.21. The seven organisms that did not exhibit metabolic efficiency are all Lactobacilli and highly auxotrophic. Saccharomyces cerevisiae exhibits significant trends between average amino acid …

Population Fit Threshold: Fully Automated Signal Map Generation For Baseline Correction In Nmr-Based Metabolomics, Daniel C. Homer

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Baseline correction of NMR-based metabolomic spectra is a key step in data processing to elucidate biomarkers of diseased and toxic states. Automated baseline correction methods often use human-selected parameters. Presented is a method for automated baseline correction using parameters selected from and without manipulation of the spectrum. The focus is on generating an accurate signal map based on the differentiating characteristics of baseline noise and signal. The presented method of signal map generation and baseline correction was developed and tested on 13C and 1H NMR spectra. The spectra were as simple as chemical standards containing less than 25 signal peaks …

Induction Of P53 Dependent Cellular Senescence Through Hdmx Inhibition Or Ypel3 Expression, Kelly Lynn Robbins Miller

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Mutations in p53 that compromise its function have been reported in approximately half of all human cancers (Vousden et al., 2002). The other half of human tumors that retain wild-type p53 have a dysfunctional p53 pathway through other mechanisms (Wade et al., 2009). Activation of p53 leads to cell cycle arrest, DNA repair, apoptosis and senescence, however, the pathway leading to cellular senescence is the focus of this study. Cellular senescence is a process leading to irreversible arrest of cell division. Under normal physiologic conditions, the activity of p53 is kept in check by its negative regulators, Mdm2 and MdmX. …

Cytochrome C Oxidase From Rhodobacter Sphaeroides: Oligomeric Structure In The Phospholipid Bilayer And The Structural And Functional Effects Of A C-Terminal Truncation In Subunit Iii, Teresa L. Cvetkov

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Cytochrome c oxidase (COX) of the mitochondrial electron transport chain catalyzes the reduction of oxygen to water while concomitantly translocating protons across the inner mitochondrial membrane. This two part dissertation is a structural and functional investigation of COX using the bacterial model system from Rhodobacter sphaeroides (R.sph.).

First, the oligomeric structure of R.sph. COX within the lipid bilayer was investigated using discontinuous sucrose gradient ultracentrifugation. Utilizing this technique, liposomes containing R.sph. COX (pCOV) were separated from liposomes lacking enzyme (COV). The net buffering capacity and degree of light scattering per COX molecule were reduced in pCOVs, making them well suited …

Finding Cadaveric Human Head Masses And Center Of Gravity: A Comparison Of Direct Measurement To 3d Ing, Grant Corwin Roush

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Mass properties of the human head are critical elements in developing neck injury threshold criteria in acceleration and impact environments. In order to accurately simulate the dynamics of the head in impact and acceleration environments, valid mass properties data for the human head must exist.

The purpose of this study was two-fold: First, to directly measure and generate a useful data set of human head mass properties and anthropometry, and second, compare the results from the direct measurement to measurements obtained using computed tomographic (CT) analyses of the human head. Four cadaveric human heads, all male, were measured.

For the …

Computer-Based Skeletal Age Assessment Using Hand/Wrist Radiographs In Children 8-18 Years Old, Zhihong Ni

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Children's skeletons mature at different rates, and they can be affected by a variety of factors including disease, hormone imbalance or genetics. The assessment of skeletal maturity is a frequently performed procedure that allows the detection of hormonal, growth or genetic disorders. Several methods have been developed to estimate skeletal maturity. Most methods evaluate hand/wrist radiographs using indicators such as the ratios of various bone widths, the onset of the ossification of epiphysis and epiphyseal-diaphyseal fusion. Among those methods, the FELS method differs from others in the application of different grades to each indicator and the provision of a confidence …

Charaterization Of Chlorpyrifos Toxicity On The Pancreatic Beta Cell Line Rinm5f, Zhongyu Yan

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Chlorpyrifos (CPF) is a well-known organophosphate (OP) insecticide that inhibits acetylcholinesterase (AChE). Organophosphates have been shown to induce hyperglycemia in both humans and animals that cannot be explained by AChE inhibition alone. Pancreatic β-cells are responsible for secreting insulin and playing a fundamental role in glucose homeostasis. The aim of this research was to investigate CPF toxicity on the insulin secreting β-cell line RINm5f (RIN). In the first part of this dissertation, we determined that cytotoxic concentrations of CPF between 50 µM and 200 µM induced a dose-dependent increase in RIN cell apoptotic and necrotic death (p<0.05). Lower doses, i.e., 5-25 µM did not induce apoptosis or necrosis. In further mechanistic studies, inhibitors of c-Jun N-terminal kinase (JNK) and P38 pathways, i.e., SP600125 and SB202190, successfully attenuated CPF-induced apoptosis (p<0.05), suggesting cell death is mediated by JNK and/or p38. In addition, N-Acetyl-L-cysteine (NAC), an antioxidant, inhibited apoptosis suggesting that oxidative stress is also involved in RIN cell death. In the second part of this dissertation, low dose CPF's effects on insulin synthesis and secretion was studied. Our results showed that RIN cells treated with CPF for 4 hr exhibited a dose-dependent decrease in insulin secretion in response to stimulation by 50 mM potassium (p<0.05). Insulin secretion stimulated by 25 mM glucose also showed significant decreases upon incubation with various doses of CPF (p<0.05). Insulin synthesis involves proteolytic cleavage of proinsulin at two specific sites. The enzymes responsible for promoting proinsulin cleavage, i.e, prohormone convertase (PC) 1/3 and 2 (PC2), contain a serine hydrolase catalytic triad, His-Asp-Ser, similar to AChE. CPF modification of PC enzymes similar to AChE, could potentially interrupt the conversion of proinsulin to insulin and disrupt insulin secretion. PC2 enzyme activity was significantly inhibited by CPF at concentrations as low as 10 µM (p<0.01). RIN cells, for the first time, were found to secrete proinsulin was through a constitutive instead of a regulated pathway. In summary, our results show that CPF not only exerts a direct cytotoxic effect at concentrations above 50 µM, but also significantly impairs insulin secretion at lower doses. Low dose CPF could potentially affect endocrine function in vivo by inhibiting the proinsulin processing enzyme PC2.

Radio Frequency Controlled Stimulation Of Intracellular Gold Or Silver Nanoparticle Conjugates For Use As Potential Sensors Or Modulators Of Biological Function, Richard Craig Murdock

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The objective of this investigation was to further explore the ability of a radio frequency (RF) signal to interact with metal nanoparticles (NPs) for the purposes of remote stimulation or control of cellular processes. Gold and silver NPs have shown the ability to be heated by electromagnetic frequencies, especially for the purpose of deactivating abnormal cells. However, the heating of the NPs in these previous studies was constant and uncontrolled. For this study, our hypothesis was by investigating the RF heating characteristics of NPs and its impact on surface functionalizations, a remotely stimulated control mechanism can be developed at the …

Characterization And Improvement Of A Cone-Beam Ct Scanner For Quantitative Imaging, Jimish Dilip Joshi

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Computed tomography (CT) has various applications in different fields. In our case, the cone-beam CT scanner is used in the industrial field for qualitative and quantitative assessment of Procter and Gamble products. The Flash CT scanner, on which we do our research, has a microfocus x-ray tube, a detector size of 30 cm x 40 cm and a rotating stage for the object to be imaged. The x-ray tube can be operated up to 225 kV. Non-linearities in the response of the detector, scatter and beam hardening may cause false interpretations of the image values. To allow appropriate assessment of …

Cellular Effects Of Replicating A Polypurine-Polypyrimidine Sequence And The Interactions Of Due-B With Replication Proteins, Shere Lynne Myers

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This work investigates two questions regarding DNA replication. The first aim examines the interactions of DUE-B with replication proteins and the second explores the cellular effects of replicating a polypurine polypyrimidine sequence in human cells.

DUE-B siRNA decreases the chromatin binding of essential replication proteins Cdc45, PCNA and RPA. DUE-B also co-immunoprecipitates with Cdc45 and TopBP1. In vitro kinase assays suggest that the checkpoint protein ATR may phosphorylate DUE-B. These experiments lend further evidence that DUE-B plays an important role in the initiation of eukaryotic DNA replication.

To investigate the effects of replicating a polypurine-polypyrimidine sequence prone to secondary structure …

Distribution Tridimensionnelle De La Lumière Dans Une Strucutre De Tête D’Adulte Dérivée D’Un Acte Irm: Approche Par La Méthode De Monte Carlo, Chemseddine Mansouri, Jean-Pierre L'Huillier, Nasser H. Kashou

Biomedical, Industrial & Human Factors Engineering Faculty Publications

No abstract provided.

Differential Regulation Of Vitamin D Receptor (Vdr) By P53, P63 And P73, Ramakrishna Kommagani

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The tumor suppressor p53 is the single most altered gene in human cancers. p53 homologues, p63 and p73 play a major role in development and in human cancer. Both p63and p73-null mice exhibit profound developmental abnormalities, suggesting a vital role for p63 and p73 in development. Although the role of p73 in human cancers is well established, the role of p63 still remains to be understood. While p63 plays a major role in development, p73 plays a major role in tumor suppression as well as in development. Although a functional co-operation is evident between each member of p53 family, additional …

Cellular Function Of The Ia-Motoneuron Circuit Following Peripheral Nerve Regeneration, Katie Leigh Bullinger

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Successful regeneration of a severed peripheral nerve is insufficient to restore the stretch reflex. This deficit occurs despite successful muscle reinnervation and functional restoration of the circuit components. For example, Ia afferents encode muscle stretch, Ia-motoneuron synapses reform to the extent of restoring low frequency transmission, and activation of motoneurons results in muscle force output. However, when recording intracellularly from reinnervated rat motoneurons during ramp hold and release muscle stretch, no excitatory synaptic potentials are detected in 2/3 motoneurons (Haftel et al., 2005), a clear sign that the synapses connecting Ia afferents with motoneurons are physiologically disrupted. This thesis examines …

Timing-Pulse Measurement And Detector Calibration Of The Osteoquant, Binu Eapen Enchakalody

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The OsteoQuant is a second-generation pQCT scanner, which can provide precisedensity assessment of bone. The scanner is being upgraded with an x-ray tube radiation source and a semiconductor CZT detector. This thesis provides solutions for two issues: motion-detector timing and dead-time/beam-hardening corrections. During translation, the motion-control system of the scanner repositions the source and detector by small intervals. However, the detector collects photon counts asynchronously with respect to the motor-timing pulses and reads photon counts (frames) at regular intervals based on its own clock. Since there needs to be correspondence between source/detector location and detector readout, the first part of …

Ion Transport Mechanisms During Hyposmotic Regulatory And Isosmotic Apoptotic Volume Decreases In A Human Lens Epithelial Cells Line, Ameet Ajit Chimote

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Living cells maintain constant volume in response to physiological stresses by altering trans-membrane ion, solute and water flow. In the present study, early and late membrane transport changes in human lens epithelial (HLE-B3) cells under hyposmotic and apoptotic stress were compared. Cell potassium (Ki), rubidium (Rbi)-uptake and water content were measured by atomic absorption spectrophotometry and gravimetry, respectively. Intracellular chloride concentration [Cl]i was determined with the fluorescence dye N- (ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE), during regulatory volume decrease (RVD) after hyposmotic stress and apoptotic volume decrease (AVD) induced by staurosporine (STP), a protein-kinase inhibitor. Cell water increased in hyposmotic balanced salt solution …

The In Vitro Interactions Between Tubulin And Hiv-1 Rev Require Rev's Multimerization And Arginine-Rich Motifs, Amit Sharma

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Rev is a 13 kDa regulatory HIV protein essential for viral replication. It trans-activates expression of late viral proteins by multimerizing onto target mRNA and promoting their export into the cytoplasm. During attempts to find the solution conditions needed to study Rev structure, Watts et al. (2000) discovered that Rev depolymerizes microtubules (MTs) in vitro through the formation of ringed tubulin intermediates called Rev-tubulin toroids (RTTs). Rev interactions with MTs are specific and are thought to mimic the mechanism of Kinesin-13 proteins, themselves potent MT depolymerases that regulate the assembly of the mitotic spindle. If Rev and Kinesin-13 proteins share …

Graphical User Interface (Gui) To Study Different Reconstruction Algorithms In Computed Tomography, Shital K. Abhange

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Computed tomography (CT) imaging relies on computational algorithms to reconstruct images from projections gathered from the CT scan. Depending on the scanner geometry, different types of reconstruction algorithms can be used. To study these different types of reconstruction algorithms in a user-friendly way, a software tool was built. The aim of the thesis was to provide a software platform to access a number of previously implemented reconstruction algorithms with ease and minimal knowledge of the reconstruction code. The goal was accomplished by building a Graphical User Interface (GUI) using MATLAB 7.7.0 (R2008b). In addition to creating mathematical objects and invoking …

Small Conductance Calcium-Activated Potassium (Sk) Channels In Mammalian Spinal Motoneurons, Zhihui Deng

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Three homologous small conductance calcium-activated potassium (SK) channel subunits (SK1, SK2, and SK3) are expressed in distinct and overlapping patterns in mammalian central nervous system. SK channels likely mediate the medium afterhyperpolarization (mAHP), which plays an essential role in regulating neuron repetitive firing frequency. In spinal motoneurons (MNs) the mAHP duration is shorter on average in fast (F-type) MNs than that in slow (S-type) MNs. To better understand the molecular basis for mAHP, we determined the expression and sub-cellular distribution of SK channels in normal, axonally-injured, and developing spinal MNs in vivo using immunohistochemistry and quantitative confocal imaging techniques.

SK2 …

Induction Of Socs-1 In Hsv-1-Infected Murine Keratinocytes: A Mechanism Of Inhibition Of Interferon Gamma, Kenneth Gene Frey

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Epidermal cells such as keratinocytes are the major site of Herpes Simplex Virus Type 1 (HSV-1) replication in active primary or recurring herpes infection. In this study, a murine keratinocyte cell line (HEL-30) was shown to be refractory to IFNγ induction of an antiviral state to HSV-1 infection, while IFNγ did induce an antiviral state in a murine fibroblast cell line (L929). Particularly, IFN-gamma and its peptide mimetic protected fibrobasts from viral-induced cytopathic effect while the keratinocytes were destroyed by the infection. Suppressor of cytokine synthesis-1 (SOCS-1) a negative regulator of IFNγ, was hypothesized to be responsible for the refractiveness …

Embryonic And Postnatal Development Of The Neural Circuitry Involved In Motor Control, Valerie Cari Ann Siembab

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The development of locomotion is believed to result from the maturation of the spinal circuits controlling motor output, however little is known about its mechanisms. To shed some light into this process we studied the development of the synaptic connectivity of two spinal inhibitory interneurons. Adult motoneurons are controlled by inhibitory networks that include recurrent and reciprocal inhibition (Pierrot-Deseilligny & Burke, 2005). Each is modulated by different ventral horn spinal interneurons that display synaptic connectivity adapted to their function: Renshaw cells (RCs) mediate recurrent inhibition, receive excitatory inputs from motor axons and inhibit homonymous and synergistic motoneurons; while Ia inhibitory …