Decoding complete reach and grasp actions from local primary motor cortex populations.

How the activity of populations of cortical neurons generates coordinated multijoint actions of the arm, wrist, and hand is poorly understood. This study combined multielectrode recording techniques with full arm motion capture to relate neural activity in primary motor cortex (M1) of macaques (Macaca mulatta) to arm, wrist, and hand postures during movement. We find that the firing rate of individual M1 neurons is typically modulated by the kinematics of multiple joints and that small, local ensembles of M1 neurons contain sufficient information to reconstruct 25 measured joint angles (representing an estimated 10 functionally independent degrees of freedom). Beyond showing that the spiking patterns of local M1 ensembles represent a rich set of naturalistic movements involving the entire upper limb, the results also suggest that achieving high-dimensional reach and grasp actions with neuroprosthetic devices may be possible using small intracortical arrays like those already being tested in human pilot clinical trials.

Calvarial defects associated with neurofibromatosis type 1. Report of two cases.

Calvarial osteolysis is a relatively rare finding in patients with neurofibromatosis. The authors describe two patients with neurofibromatosis Type 1 (NF1) and extensive cranial defects associated with underlying dural ectasia. Cranioplasties were performed in both patients with mixed results. One patient underwent cranioplasty using titanium mesh and methylmethacrylate. The other patient underwent an extensive cranioplasty with autogenous iliac crest grafting, and after initial healing has since had further bone resorption. In conclusion, the results of cranial reconstruction in patients with NF1 and dural ectasia are unpredictable because of the tendency for further bone resorption; techniques that protect the graft material from cerebrospinal fluid pulsations via a rigid mesh should be considered.

Nesprin-1alpha self-associates and binds directly to emerin and lamin A in vitro.

Nesprin-1alpha is a spectrin repeat (SR)-containing, transmembrane protein of the inner nuclear membrane, and is highly expressed in muscle cells. A yeast two-hybrid screen for nesprin-1alpha-interacting proteins showed that nesprin-1alpha interacted with itself. Blot overlay experiments revealed that nesprin-1alpha's third SR binds the fifth SR. The carboxy-terminal half of nesprin-1alpha directly bound lamin A, a nuclear intermediate filament protein. Biochemical analysis demonstrated that nesprin-1alpha dimers bind directly to the nucleoplasmic domain of emerin, an inner nuclear membrane protein, with an affinity of 4 nM. Binding was optimal for full nucleoplasmic dimers of nesprin-1alpha, since nesprin fragments SR1-5 and SR5-7 bound emerin as monomers with affinities of 53 nM and 250 mM, respectively. We propose that membrane-anchored nesprin-1alpha antiparallel dimers interact with both emerin and lamin A to provide scaffolding at the inner nuclear membrane.

Origins of intraoperative MRI.

Neurosurgical diagnosis and intervention has evolved through improved neuroimaging, allowing better visualization of anatomy and pathology. This article discusses the various systems that have been designed over the last decade to meet the requirements of neurosurgical patients and opines on the potential future developments in the technology and application of intraoperative MRI. Because the greatest amount of experience with intraoperative MRI comes from its use in brain tumor resection, this article focuses on the origins of intraoperative MRI in relation to this field.

Origins of intraoperative MRI.

Neurosurgical diagnosis and intervention has evolved through improved neuroimaging, allowing better visualization of anatomy and pathology. This article discusses the various systems that have been designed over the last decade to meet the requirements of neurosurgical patients and opines on the potential future developments in the technology and application of intraoperative MRI. Because the greatest amount of experience with intraoperative MRI comes from its use in brain tumor resection, this article focuses on the origins of intraoperative MRI in relation to this field.

Ovarian Teratoma Masquerading as a CSF Pseudocyst in a Female with a Ventriculoperitoneal Shunt.

Background. In today's fast-paced and high-acuity emergency departments, clinicians are often compelled to triage cases so rapidly that a differential diagnosis consistent with the history and physical examination is not comprehensive. Case Report. This case report describes the unexpected finding of a cystic ovarian neoplasm in a young female with an abdominal mass and a ventriculoperitoneal shunt, initially diagnosed as a cerebrospinal fluid pseudocyst. We use this case to illustrate that the astute clinician must always synthesize a diagnosis from all data sources and not to rely on initial radiographic evaluations. Conclusions. This remarkable case demonstrates that all differential diagnoses must be entertained in order to rapidly and accurately diagnose a patient with a cystic abdominal mass.

Pediatric disk disease.

Intervertebral disk herniation in pediatric patients is a rare but potentially disabling entity that is frequently difficult to diagnose. This article reviews the fundamentals of pediatric intervertebral disk herniation with the intention of presenting a rational and simple strategy for the evaluation and treatment of disk herniation in children, with specific emphasis on how it differs from adult disk disease in presentation, pathologic findings, and treatment options.

Nesprin-1alpha contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope.

Muscle A-kinase anchoring protein (mAKAP) is a scaffold protein found principally at the nuclear envelope of striated myocytes. mAKAP maintains a complex consisting of multiple signal transduction molecules including the cAMP-dependent protein kinase A, the ryanodine receptor calcium release channel, phosphodiesterase type 4D3, and protein phosphatase 2A. By an unknown mechanism, a domain containing spectrin repeats is responsible for targeting mAKAP to the nuclear envelope. We now demonstrate that the integral membrane protein nesprin-1alpha serves as a receptor for mAKAP on the nuclear envelope in cardiac myocytes. Nesprin-1alpha is inserted into the nuclear envelope by a conserved, C-terminal, klarsicht-related transmembrane domain and forms homodimers by the binding of an amino-terminal spectrin repeat domain. Through the direct binding of the nesprin-1alpha amino-terminal dimerization domain to the third mAKAP spectrin repeat, nesprin-1alpha targets mAKAP to the nuclear envelope. In turn, overexpression of these spectrin repeat domains in myocytes can displace mAKAP from nesprin-1alpha.

Cytoskeletal defects in cardiomyopathy.

Genetic studies of cardiomyopathy and muscular dystrophy have emphasized the importance of the striated myocyte cytoskeleton. Cytoskeletal defects produce myopathies through a combination of structural and signaling mechanisms. Broadly, the cytoskeletal proteins defective in these myopathic syndromes can be classified into categories based on their intracellular locations. The first category includes proteins of the plasma membrane that interact with both subsarcolemmal and extracellular matrix proteins. The second category, generally associated with hypertrophic cardiomyopathies, includes proteins of the sarcomere. The last, newly emerging, category includes proteins of the inner nuclear membrane. In this review, we will examine the genetic defects that lead to cardiomyopathy and the potential means by which these varied proteins normally maintain the structural integrity of myocytes.

Myne-1, a spectrin repeat transmembrane protein of the myocyte inner nuclear membrane, interacts with lamin A/C.

Mutations in the genes encoding the inner nuclear membrane proteins lamin A/C and emerin produce cardiomyopathy and muscular dystrophy in humans and mice. The mechanism by which these broadly expressed gene products result in tissue-specific dysfunction is not known. We have identified a protein of the inner nuclear membrane that is highly expressed in striated and smooth muscle. This protein, myne-1 (myocyte nuclear envelope), is predicted to have seven spectrin repeats, an interrupted LEM domain and a single transmembrane domain at its C-terminus. We found that myne-1 is expressed upon early muscle differentiation in multiple intranuclear foci concomitant with lamin A/C expression. In mature muscle, myne-1 and lamin A/C are perfectly colocalized, although colocalization with emerin is only partial. Moreover, we show that myne-1 and lamin A/C coimmunoprecipitate from differentiated muscle in vitro. The muscle-specific inner nuclear envelope expression of myne-1, along with its interaction with lamin A/C, indicates that this gene is a potential mediator of cardiomyopathy and muscular dystrophy.

Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene.

Mutations in the LMNA gene encoding nuclear lamins A and C are responsible for seven inherited disorders affecting specific tissues. We have analyzed skin fibroblasts from a patient with type 1B limb-girdle muscular dystrophy and from her deceased newborn grandchild carrying, respectively, a heterozygous (+/mut) and a homozygous (mut/mut) nonsense Y259X mutation. In fibroblasts(+/mut), the presence of only 50% lamins A and C promotes no detectable abnormality, whereas in fibroblasts(mut/mut) the complete absence of lamins A and C leads to abnormally shaped nuclei with lobules in which none of the analyzed nuclear proteins were detected, i.e., B-type lamins, emerin, nesprin-1alpha, LAP2beta, and Nup153. These lobules perturb cell division as fibroblast(mut/mut) cultures with large proportions of cells with dysmorphic nuclei grow more slowly than controls and the cell proliferation normalizes when the number of these abnormally shaped nuclei declines. In all fibroblasts(mut/mut), nesprin-1alpha-like emerin exhibited aberrant localization in the endoplasmic reticulum. Transfection of wild-type lamin A or C cDNAs restored the correct localization of both emerin and nesprin-1alpha. These data demonstrate that lamin C, like lamin A, interacts in vivo directly with nesprin-1alpha and with emerin and that lamin A or C is sufficient for the correct anchorage of emerin and nesprin-1alpha at the nuclear envelope in human cells.