Bone grafting in oblique versus prepared rectangular uncontained glenoid defects in reversed shoulder arthroplasty. A biomechanical comparison.

Background: How the shape of the glenoid defect being reconstructed influences stability in reversed shoulder arthroplasty has never been evaluated. The purpose of this study was to compare the reconstruction of two different shaped defects in reversed shoulder arthroplasty.

Methods: Two groups (ten Sawbone scapulae each) of oblique- and rectangular-shaped glenoid defects were tested biomechanically.

Biomechanical analysis of anterior bone graft augmentation with reversed shoulder arthroplasty in large combined glenoid defects compared with total bony joint line reconstruction (modified bony-increased-offset reversed shoulder arthroplasty).

Background: The aim of this biomechanical study was to compare 2 surgical techniques for the reconstruction of large, combined, uncontained glenoid defects with reversed shoulder arthroplasty (RSA).

Methods: Three groups of scapulae with RSA were tested by the application of a physiological combination of compressive/shear loads in Sawbones (Pacific Research Laboratories, Inc., Vashon Island, WA, USA) and cadavers.

Effects on channel properties and induction of cell death induced by c-terminal truncations of pannexin1 depend on domain length.

Pannexin1 (Panx1) is an integral membrane protein and known to form multifunctional hexameric channels. Recently, Panx1 was identified to be responsible for the release of ATP and UTP from apoptotic cells after site-specific proteolysis by caspases 3/7. Cleavage at the carboxy-terminal (CT) position aa 376-379 irreversibly opens human Panx1 channels and leads to the release of the respective nucleotides resulting in recruitment of macrophages and in subsequent activation of the immunologic response.

Internal ribosomal entry site (IRES) activity generates endogenous carboxyl-terminal domains of Cx43 and is responsive to hypoxic conditions.

Connexin43 (Cx43) is the most abundant gap junction protein in higher vertebrate organisms and has been shown to be involved in junctional and non-junctional functions. In addition to the expression of full-length Cx43, endogenously produced carboxyl-terminal segments of Cx43 have been described and have been suggested to be involved in manifold biological functions, such as hypoxic preconditioning and neuronal migration. Molecular aspects, however, behind the separate generation of carboxyl-terminal segments of Cx43 have remained elusive.

Comparative pilot study of implantation techniques for pudendal neuromodulation: technical and clinical outcome in first 20 patients with chronic pelvic pain.

Purpose: Neurostimulation of the pudendal nerve (PN) is considered for patients who have failed sacral neuromodulation. Previous techniques for PN localization are described to be uncomplicated and promise to achieve accuracy in electrode placement. However, in clinical use, they appear challenging.

Pannexin1 channel proteins in the zebrafish retina have shared and unique properties.

In mammals, a single pannexin1 gene (Panx1) is widely expressed in the CNS including the inner and outer retinae, forming large-pore voltage-gated membrane channels, which are involved in calcium and ATP signaling. Previously, we discovered that zebrafish lack Panx1 expression in the inner retina, with drPanx1a exclusively expressed in horizontal cells of the outer retina. Here, we characterize a second drPanx1 protein, drPanx1b, generated by whole-genome duplications during teleost evolution.

Pannexin1 stabilizes synaptic plasticity and is needed for learning.

Pannexin 1 (Panx1) represents a class of vertebrate membrane channels, bearing significant sequence homology with the invertebrate gap junction proteins, the innexins and more distant similarities in the membrane topologies and pharmacological sensitivities with gap junction proteins of the connexin family. In the nervous system, cooperation among pannexin channels, adenosine receptors, and K(ATP) channels modulating neuronal excitability via ATP and adenosine has been recognized, but little is known about the significance in vivo. However, the localization of Panx1 at postsynaptic sites in hippocampal neurons and astrocytes in close proximity together with the fundamental role of ATP and adenosine for CNS metabolism and cell signaling underscore the potential relevance of this channel to synaptic plasticity and higher brain functions.

Calmodulin dependent protein kinase increases conductance at gap junctions formed by the neuronal gap junction protein connexin36.

The major neuronal gap junction protein connexin36 (Cx36) exhibits the remarkable property of "run-up", in which junctional conductance typically increases by 10-fold or more within 5-10min following cell break-in with patch pipettes. Such conductance "run-up" is a unique property of Cx36, as it has not been seen in cell pairs expressing other connexins. Because of the recent observation describing CaMKII binding and phosphorylation sites in Cx36 and evidence that calmodulin dependent protein kinase II (CaMKII) may potentiate electrical coupling in neurons of teleosts, we have explored whether CaMKII activates mammalian Cx36.

Neuroglial activation and Cx43 expression are reduced upon transplantation of human umbilical cord blood cells after perinatal hypoxic-ischemic injury.

Glial cells play a crucial role in the pathomechanism of perinatal hypoxic-ischemic brain injury (HI) and are involved in the maintenance of a chronic state of inflammation that causes delayed neuronal damage. Activation of astrocytes is one factor prolonging brain damage and contributing to the formation of a glial scar that limits neuronal plasticity. In this context, the major astrocytic gap junction protein Connexin 43 (Cx43) has been ascribed various functions including regulation of astrocytic migration and proliferation.

Connexins and Cap-independent translation: role of internal ribosome entry sites.

Cap-independent translation using an internal ribosome entry site instead of the 5'-Cap structure has been discovered in positive-sense RNA viruses and eukaryotic genomes including a subset of gap junction forming connexins genes. With a growing number of mutations found in human connexin genes and studies on genetically modified mouse models mechanisms highlighting the important role of gap junctional communication in multicellular organism it is obvious that mechanism need to be in place to preserve this critical property even under conditions when Cap-mediated translation is scrutinized. To ensure sustained gap junctional communication, rapid initiation of translation of preexisting connexin mRNAs is one possibility, and the presence of internal ribosome entry sites in gap junction genes comply with such a requirement.

Transplantation of human umbilical cord blood cells mediated beneficial effects on apoptosis, angiogenesis and neuronal survival after hypoxic-ischemic brain injury in rats.

Transplantation of human umbilical cord blood (hucb) cells in a model of hypoxic-ischemic brain injury led to the amelioration of lesion-impaired neurological and motor functions. However, the mechanisms by which transplanted cells mediate functional recovery after brain injury are largely unknown. In this study, the effects of hucb cell transplantation were investigated in this experimental paradigm at the cellular and molecular level.

Single cysteines in the extracellular and transmembrane regions modulate pannexin 1 channel function.

Pannexins form high-conductance ion channels in the membranes of many vertebrate cells. Functionally, they have been associated with multiple functional pathways like the propagation of calcium waves, ATP release, responses to ischemic conditions and apoptosis. In contrast to accumulating details which uncovered their functions, the molecular mechanisms for pannexin channel regulation and activation are hardly understood.

Olfactory neuron-specific expression of A30P α-synuclein exacerbates dopamine deficiency and hyperactivity in a novel conditional model of early Parkinson's disease stages.

Mutations in the N-terminus of the gene encoding α-synuclein (α-syn) are linked to autosomal dominantly inherited Parkinson's disease (PD). The vast majority of PD patients develop neuropsychiatric symptoms preceding motor impairments. During this premotor stage, synucleinopathy is first detectable in the olfactory bulb (OB) and brain stem nuclei; however its impact on interconnected brain regions and related symptoms is still less far understood.

Ccdc66 null mutation causes retinal degeneration and dysfunction.

Retinitis pigmentosa (RP) is a group of human retinal disorders, with more than 100 genes involved in retinal degeneration. Canine and murine models are useful for investigating human RP based on known, naturally occurring mutations. In Schapendoes dogs, for example, a mutation in the CCDC66 gene has been shown to cause autosomal recessively inherited, generalized progressive retinal atrophy (gPRA), the canine counterpart to RP.

Electromagnetic field effect or simply stress? Effects of UMTS exposure on hippocampal longterm plasticity in the context of procedure related hormone release.

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions.

Unified patch clamp protocol for the characterization of Pannexin 1 channels in isolated cells and acute brain slices.

In the central nervous system, Pannexin 1 (Panx1) channels are implicated in a variety of physiological and pathological conditions. One of the prerequisites to enlighten the role of Panx1 is the development and standardization of reliable methods. Here, we address the applicability of voltage clamp protocols to identify Panx1 channel mediated currents in neurons of acutely dissected brain slices.

In vitro motility of liver connexin vesicles along microtubules utilizes kinesin motors.

Trafficking of the proteins that form gap junctions (connexins) from the site of synthesis to the junctional domain appears to require cytoskeletal delivery mechanisms. Although many cell types exhibit specific delivery of connexins to polarized cell sites, such as connexin32 (Cx32) gap junctions specifically localized to basolateral membrane domains of hepatocytes, the precise roles of actin- and tubulin-based systems remain unclear. We have observed fluorescently tagged Cx32 trafficking linearly at speeds averaging 0.

Pannexin channels are not gap junction hemichannels.

Pannexins, a class of membrane channels, bear significant sequence homology with the invertebrate gap junction proteins, innexins and more distant similarities in their membrane topologies and pharmacological sensitivities with the gap junction proteins, connexins. However, the functional role for the pannexin oligomers, or pannexons, is different from connexin oligomers, the connexons. Many pannexin publications have used the term "hemichannels" to describe pannexin oligomers while others use the term "channels" instead.

Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes.

A large conductance (∼300 picosiemens) channel (LCC) of unknown molecular identity, activated by Ca(2+) release from the sarcoplasmic reticulum, particularly when augmented by caffeine, has been described previously in isolated cardiac myocytes. A potential candidate for this channel is pannexin 1 (Panx1), which has been shown to form large ion channels when expressed in Xenopus oocytes and mammalian cells. Panx1 function is implicated in ATP-mediated auto-/paracrine signaling, and a crucial role in several cell death pathways has been suggested.

Anti-inflammatory effects of the anticonvulsant drug levetiracetam on electrophysiological properties of astroglia are mediated via TGFβ1 regulation.

Background And Purpose: The involvement of astrocytes as immune-competent players in inflammation and the pathogenesis of epilepsy and seizure-induced brain damage has recently been recognized. In clinical trials and practice, levetiracetam (LEV) has proven to be an effective antiepileptic drug (AED) in various forms of epileptic seizures, when applied as mono- or added therapy. Little is known about the mechanism(s) of action of LEV.

Non-viral siRNA delivery into the mouse retina in vivo.

Background: Gene silencing in the retina using RNA interference could open broad possibilities for functional studies of genes in vivo and for therapeutic interventions in eye disorders. Therefore, there is a considerable demand for protocols to deliver siRNA into the vertebrate retina. In this work we explored a possibility to deliver synthetic 21 bp siRNA into the mouse retina after intravitreal application using a non-viral carrier.

Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity.

Pannexins constitute a family of proteins exhibiting predominantly hemichannel activity. Pannexin channels have been suggested to participate in a wide spectrum of biological functions such as propagation of calcium waves, release of IL-1β, and responses to ischemic conditions. At present, the molecular mechanisms regulating pannexin hemichannel activity are essentially unknown.

Gap junctions in inherited human disease.

Gap junctions (GJ) provide direct intercellular communication. The structures underlying these cell junctions are membrane-associated channels composed of six integral membrane connexin (Cx) proteins, which can form communicating channels connecting the cytoplasms of adjacent cells. This provides coupled cells with a direct pathway for sharing ions, nutrients, or small metabolites to establish electrical coupling or balancing metabolites in various tissues.