| Untangling the cortex: Advances in understanding specification and differentiation of corticospinal motor neurons.
January 29, 2010 at 9:29 AM
|
| | Untangling the cortex: Advances in understanding specification and differentiation of corticospinal motor neurons. Bioessays. 2010 Jan 27; Authors: Shoemaker LD, Arlotta P The mature cerebral cortex contains a staggering variety of projection neuron subtypes, and a number of complementary studies have recently begun to define their identity and embryonic origin. Among the different types of cortical projection neurons, subcerebral projection neurons, including corticospinal motor neurons (CSMN), have been extensively studied and some of the molecular controls over their differentiation have been elucidated. Here, we first provide an overview of the approaches used to purify and molecularly profile neuronal populations of the neocortex and, more broadly, of the central nervous system (CNS). Next, we specifically review recent progress in understanding the genes that define and control development of the CSMN population. Finally, we briefly discuss the relevance of this work to current questions regarding the mechanisms of the establishment of projection neuron subtype identity in the neocortex and its implications to direct the diffe! rentiation of CSMN for therapeutic benefit. PMID: 20108227 [PubMed - as supplied by publisher] | | |
| Direct conversion of fibroblasts to functional neurons by defined factors.
January 29, 2010 at 9:29 AM
|
| | Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010 Jan 27; Authors: Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Genera! tion of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine. PMID: 20107439 [PubMed - as supplied by publisher] | | |
| Mutations in a gene encoding a midbody protein in binucleated Reed-Sternberg cells of Hodgkin lymphoma.
January 29, 2010 at 9:29 AM
|
| | Mutations in a gene encoding a midbody protein in binucleated Reed-Sternberg cells of Hodgkin lymphoma. Cell Cycle. 2010 Feb 30;9(4) Authors: Krem MM, Salipante SJ, Horwitz MS Classical Hodgkin lymphoma (cHL) is a cancer in which malignant "Reed-Sternberg" cells comprise just a fraction of the bulk of the tumor and are characteristically binucleated. We recently identified a novel gene, KLHDC8B, which appears responsible for some familial cases of cHL. KLHDC8B encodes a midbody kelch protein expressed during cytokinesis. Deficiency of KLHDC8B leads to binucleated cells, implicating its involvement in Reed-Sternberg cell formation. Interestingly, other cancer genes, such as BRCA1 and BRCA2, also encode proteins locating to the midbody during cytokinesis, even though their participation in other pathways has received greater attention. Midbody components may be an overlooked source of tumor suppressor genes. PMID: 20107318 [PubMed - as supplied by publisher] | | |
| Engineering an artificial alveolar-capillary membrane: a novel continuously perfused model within microchannels.
January 29, 2010 at 9:29 AM
|
| | Engineering an artificial alveolar-capillary membrane: a novel continuously perfused model within microchannels. J Pediatr Surg. 2010 Jan;45(1):45-51 Authors: Nalayanda DD, Wang Q, Fulton WB, Wang TH, Abdullah F INTRODUCTION: Pulmonary hypoplasia is a condition of the newborn that is characterized by underdeveloped lungs and poor outcome. One strategy in the treatment of patients with hypoplasia is to augment underdeveloped lungs using biocompatible artificial lung tissue. However, one central challenge in current pulmonary tissue engineering efforts remains the development of a stable bio-mimetic alveolar-capillary membrane. Accordingly, we have built a series of bio-mimetic microfluidic devices that specifically model the alveolar-capillary membrane. Current designs include a single-layer microchip that exposes alveolar and endothelial cell types to controlled fluidic stimuli. A more advanced multi-layered device allows for alveolar cells to be cultured at an air interface while allowing constant media nourishment and waste removal, thus better mimicking the physiologic milieu of the alveolar-capillary interface. Both devices possess the benefit of parallel testing. MAT! ERIAL AND METHODS: Microdevices were fabricated using soft lithography in a biocompatible transparent polymeric material, polydimethyl siloxane, sealed covalently to glass. The multistage microdevice also integrated a suspended polyethylene terephthalate membrane connected via microfluidic channels to constant media and air access. Pulmonary endothelial (HMEC-1) and alveolar epithelial (A549) cell lines, along with fetal pulmonary cells (FPC) harvested from Swiss Webster mice at day 18 gestational age, were studied under multiple hydrodynamic shear conditions and liquid-to-cell ratio regimes. Cultures were examined for cell viability, function and proliferation to confluent monolayers. A549 cells cultured at an air-interface in a microdevice was also tested for their ability to maintain cell phenotype and function. RESULTS: The single-layer differential flow microdevice allowed for a systematic determination of the optimal growth conditions of various lung-specific cell typ! es in a microfluidic environment. Our device showed a greater ! surfacta nt based decrease in surface tension of the alveolar hypophase in A549 cultures exposed to air as compared to submerged cultures. CONCLUSIONS: We have successfully developed biomimetic microfluidic devices that specifically allow stable alveolar cell growth at the air-liquid interface. This work serves prerequisite towards an implantable artificial alveolar membrane. PMID: 20105578 [PubMed - in process] | | |
| Regenerative medicine: a surgeon's perspective.
January 29, 2010 at 9:29 AM
|
| | Regenerative medicine: a surgeon's perspective. J Pediatr Surg. 2010 Jan;45(1):11-7; discussion 17-8 Authors: Longaker MT More than 200 million incisions are made in the world each year on children and adults. They all end up with a scar unless there is an unusual situation where we are operating on an early gestation fetus. The question is, "why do we not regenerate?" and "why do we always heal with either a 'normal amount of scarring' or, approximately 15% of the time, with a pathologic amount of scarring (hypertrophic scar or keloid)?" PMID: 20105574 [PubMed - in process] | | |
| Nerve grafts and conduits.
January 29, 2010 at 9:29 AM
|
| | Nerve grafts and conduits. Plast Reconstr Surg. 2009 Dec;124(6 Suppl):e386-94 Authors: Colen KL, Choi M, Chiu DT Peripheral nerve defects are common. The surgeon faced with these problems must provide the best functional recovery for the patient with the tools provided. The ideal nerve reconstruction would create a tensionless repair with direct coaptation. However, this is not always possible and other techniques must be employed. The alternatives to direct coaptation include nerve autografts, nerve conduits, and tissue-engineered constructs. This article reviews commonly used autogenous nerve grafts and conduits. Autogenous nerve grafts have been utilized in various techniques which include the trunk graft, cable graft, interfascicular graft, and vascularized graft. The nerve conduits reviewed fall into the category of autogenous biological conduits, nonautogenous biological conduits, and nonbiological conduits. New technologies are being developed to enhance peripheral nerve regeneration with the concept that conduits can be enriched and manipulated in the laboratory to p! romote regeneration of the peripheral nerve. Further clinical studies hold the promise of successful alternatives for treating peripheral nerve injuries. PMID: 19952706 [PubMed - indexed for MEDLINE] | | |
| Clinical flap prefabrication.
January 29, 2010 at 9:29 AM
|
| | Clinical flap prefabrication. Plast Reconstr Surg. 2009 Dec;124(6 Suppl):e340-50 Authors: Guo L, Pribaz JJ Flap prefabrication and prelamination are two closely related concepts. Clinical applications of flap prefabrication and prelamination are relatively new to the field of reconstructive plastic surgery. Although the two terms are often used interchangeably in the literature, they are two distinctly different techniques. Understanding their differences is helpful in planning reconstructive strategy. They are primarily used in reconstructing complex defects where conventional techniques are not available. Flap prefabrication starts with introduction of a vascular pedicle to a desired donor tissue that on its own does not possess an axial blood supply. After a period of neovascularization of at least 8 weeks, this donor tissue can then be transferred to the recipient defect based on the newly acquired axial vasculature. Flap prelamination, in contrast, begins with building a three-dimensional structure on a reliable vascular bed. This composite structure, once matured! in approximately 2 weeks, can then be transferred to the recipient defect. This article describes in detail the principles, steps, variations, and applications of these two techniques. PMID: 19952702 [PubMed - indexed for MEDLINE] | | |
| History of microsurgery.
January 29, 2010 at 9:29 AM
|
| | History of microsurgery. Plast Reconstr Surg. 2009 Dec;124(6 Suppl):e282-94 Authors: Tamai S In the mid-1500s, the techniques of vascular ligature and vascular suture were developed sporadically by several pioneers in this field. However, vascular surgery became realistic experimentally as a result of the work by Carrel and Guthrie in the early 1900s, in which they performed replantations and transplantations of several composite tissues and organs, including amputated limbs, kidneys, and others using experimental animals. In contrast, the development of heparin by Howell and Holt in 1918 accelerated the rate of these types of operations being performed with increasing success in humans. Since the first use of a monocular microscope for ear surgery by Nylen in 1921 and a binocular microscope by Holmgren in 1923, in addition to the timely developments of the Zeiss operating microscope, microsurgical instruments, and suture materials, microsurgery was born in several surgical disciplines in the ensuing 50-year period. The application of microvascular surger! y and microneurosurgery in the fields of hand, plastic, and reconstructive surgery resulted in revolutionary advances in clinical replantation and transplantation of composite tissues and more allotransplantations. PMID: 19952697 [PubMed - indexed for MEDLINE] | | |
| Surfaces modified with nanometer-thick silver-impregnated polymeric films that kill bacteria but support growth of mammalian cells.
January 29, 2010 at 9:29 AM
|
| | Surfaces modified with nanometer-thick silver-impregnated polymeric films that kill bacteria but support growth of mammalian cells. Biomaterials. 2010 Feb;31(4):680-90 Authors: Agarwal A, Weis TL, Schurr MJ, Faith NG, Czuprynski CJ, McAnulty JF, Murphy CJ, Abbott NL Silver is widely used as a biocidal agent in ointments and wound dressings. However, it has also been associated with tissue toxicity and impaired healing. In vitro characterization has also revealed that typical loadings of silver employed in ointments and dressings (approximately 100 microg/cm(2)) lead to cytotoxicity. In this paper, we report the results of an initial study that sought to determine if localization of carefully controlled loadings of silver nanoparticles within molecularly thin films immobilized on surfaces can lead to antimicrobial activity without inducing cytotoxicity. Polymeric thin films of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) were prepared by layer-by-layer deposition and loaded with approximately 0.4 microg/cm(2) to approximately 23.6 microg/cm(2) of silver nanoparticles. Bacterial killing efficiencies of the silver-loaded films were investigated against Staphylococcus epidermidis, a gram-positive bacterium, a! nd it was determined that as little as approximately 0.4 microg/cm(2) of silver in the polymeric films caused a reduction of 6log(10)CFU/mL (99.9999%) bacteria in suspensions incubated in contact with the films (water-borne assays). Significantly, whereas the antibacterial films containing high loadings of silver were found to be toxic to a murine fibroblast cell line (NIH-3T3), the polymeric films containing approximately 0.4 microg/cm(2) of silver were not toxic and allowed attachment, and growth of the mammalian cells. Thus, the results of this study go beyond prior reports by identifying silver-impregnated, polymeric thin films that are compatible with in vitro mammalian cell culture yet exhibit antibacterial activity. These results support the hypothesis that localization of carefully controlled loadings of silver nanoparticles within molecularly thin polymeric films can lead to antimicrobial activity without cytotoxicity. More broadly, this strategy of modifying surfa! ces with minimal loadings of bioactive molecules indicates the! basis o f approaches that may permit management of microbial burden in wound beds without impairment of wound healing. PMID: 19864019 [PubMed - indexed for MEDLINE] | | |
| Altered calcium dynamics in cardiac cells grown on silane-modified surfaces.
January 29, 2010 at 9:29 AM
|
| | Altered calcium dynamics in cardiac cells grown on silane-modified surfaces. Biomaterials. 2010 Feb;31(4):602-7 Authors: Ravenscroft-Chang MS, Stohlman JM, Molnar P, Natarajan A, Canavan HE, Teliska M, Stancescu M, Krauthamer V, Hickman JJ Chemically defined surfaces were created using self-assembled monolayers (SAMs) of hydrophobic and hydrophilic silanes as models for implant coatings, and the morphology and physiology of cardiac myocytes plated on these surfaces were studied in vitro. We focused on changes in intracellular Ca(2+) because of its essential role in regulating heart cell function. The SAM-modified coverslips were analyzed using X-ray Photoelectron Spectroscopy to verify composition. The morphology and physiology of the cardiac cells were examined using fluorescence microscopy and intracellular Ca(2+) imaging. The imaging experiments used the fluorescent ratiometric dye fura-2, AM to establish both the resting Ca(2+) concentration and the dynamic responses to electrical stimulation. A significant difference in excitation-induced Ca(2+) changes on the different silanated surfaces was observed. However, no significant change was noted based on the morphological analysis. This result imp! lies a difference in internal Ca(2+) dynamics, and thus cardiac function, occurs when the composition of the surface is different, and this effect is independent of cellular morphology. This finding has implications for histological examination of tissues surrounding implants, the choice of materials that could be beneficial as implant coatings and understanding of cell-surface interactions in cardiac systems. PMID: 19828193 [PubMed - indexed for MEDLINE] | | |
| Some properties of keratin biomaterials: kerateines.
January 29, 2010 at 9:29 AM
|
| | Some properties of keratin biomaterials: kerateines. Biomaterials. 2010 Feb;31(4):585-93 Authors: Hill P, Brantley H, Van Dyke M Keratins are a family of structural proteins that can be isolated from a variety of tissues. "Soft" keratins are cytoskeletal elements found in epithelial tissues while protective tissues such as nails, hooves, and hair are composed of "hard" keratins. Hard keratins have been the subject of biomaterials investigations for more than three decades. Numerous methods exist for denaturing these proteins which are characterized by a high sulfur content and extensive disulfide bonding, under either oxidative or reductive conditions, extracting them from tissue and processing them into various physical states such as gels, films, coatings, and fibers. Kerateines or keratoses (oxidatively or reductively derived, respectively), alone or in combination with other biomaterials, have been tested in a small number of systems to demonstrate feasibility for medical applications such as wound healing, bone regeneration, hemostasis, and peripheral nerve repair. These investigations! have shown generally good compatibility with cells and tissues, but the focus of prior investigations has been fairly narrow, and as a result there is relatively little published data on the general behavior of keratin biomaterials in biological systems beyond cell culture assays. The goal of this study was to produce a reduced form of keratin biomaterial, kerateine, using a typical and well-published technique, and characterize several aspects of its behavior that may have implications to its general use as a biomaterial. Kerateines were extracted from human hair, fabricated into gels and porous scaffolds, characterized, and placed into biological systems to determine their interactions with cells and tissue. Initially, the proteins were analyzed for molecular weight and amino acid content, as well as their ability to facilitate cell adhesion and proliferation. Crosslinked hydrogels were investigated for their hydrolytic stability in vitro; the micro-architecture and in v! ivo tissue response of lyophilized gels was also studied. Thes! e experi ments both confirmed and expanded earlier findings that kerateines demonstrate excellent compatibility in biological systems. PMID: 19822360 [PubMed - indexed for MEDLINE] | | |
| Concerted stimuli regulating osteo-chondral differentiation from stem cells: phenotype acquisition regulated by microRNAs.
January 29, 2010 at 9:29 AM
|
| | Concerted stimuli regulating osteo-chondral differentiation from stem cells: phenotype acquisition regulated by microRNAs. Acta Pharmacol Sin. 2009 Oct;30(10):1369-84 Authors: Gordeladze JO, Djouad F, Brondello JM, Noël D, Duroux-Richard I, Apparailly F, Jorgensen C Bone and cartilage are being generated de novo through concerted actions of a plethora of signals. These act on stem cells (SCs) recruited for lineage-specific differentiation, with cellular phenotypes representing various functions throughout their life span. The signals are rendered by hormones and growth factors (GFs) and mechanical forces ensuring proper modelling and remodelling of bone and cartilage, due to indigenous and programmed metabolism in SCs, osteoblasts, chondrocytes, as well as osteoclasts and other cell types (eg T helper cells).This review focuses on the concerted action of such signals, as well as the regulatory and/or stabilizing control circuits rendered by a class of small RNAs, designated microRNAs. The impact on cell functions evoked by transcription factors (TFs) via various signalling molecules, also encompassing mechanical stimulation, will be discussed featuring microRNAs as important members of an integrative system. The present appro! ach to cell differentiation in vitro may vastly influence cell engineering for in vivo tissue repair. PMID: 19801995 [PubMed - indexed for MEDLINE] | | |
| The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression.
January 29, 2010 at 9:29 AM
|
| | The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression. J Invest Dermatol. 2010 Jan;130(1):74-85 Authors: Robitaille H, Simard-Bisson C, Larouche D, Tanguay RM, Blouin R, Germain L Hsp27, a small heat-shock protein, has important roles in many cellular processes, including cytoskeleton dynamics, cell differentiation, and apoptosis. Its expression in normal epidermis correlates with differentiation; however, little is known about the regulatory mechanisms involved. In this study, we report that Hsp27 undergoes upregulation, phosphorylation, and redistribution to the cytoskeleton during the late phase of epidermal keratinocyte differentiation. Our results also show that the expression of the dual leucine zipper-bearing kinase (DLK), an upstream activator of the MAP kinase pathways, is sufficient by itself to induce Hsp27 phosphorylation, cell periphery localization, and redistribution to the insoluble protein fraction (cytoskeleton) in poorly differentiated keratinocytes. This redistribution correlates with the insolubilization of cornified envelope-associated proteins such as involucrin. Interestingly, the effects of DLK on Hsp27 were blocked! by PD98059, a selective inhibitor of the extracellular signal-regulated protein kinase (ERK) pathway. Moreover, downregulation of Hsp27 by small interfering RNA in epithelial cells expressing DLK was accompanied by attenuated expression of involucrin in the cytoskeleton. Thus, these observations suggest that the DLK-ERK signaling pathway may act as a regulator of the interaction that occurs between Hsp27 and the cytoskeleton during the formation of the cornified cell envelope, a process conferring to the skin its crucial barrier function. PMID: 19675578 [PubMed - indexed for MEDLINE] | | |
| High molecular weight blood group A trisaccharide-polyacrylamide glycoconjugates as synthetic blood group A antigens for anti-A antibody removal devices.
January 29, 2010 at 9:29 AM
|
| | High molecular weight blood group A trisaccharide-polyacrylamide glycoconjugates as synthetic blood group A antigens for anti-A antibody removal devices. J Biomed Mater Res B Appl Biomater. 2009 Nov;91(2):845-54 Authors: Alikhani A, Korchagina EY, Chinarev AA, Bovin NV, Federspiel WJ Specific immunoadsorption of blood group antibodies by synthetic antigens immobilized on support matrices in the peri-transplantation period provides a promising solution to hyperacute rejection risk following ABO-incompatible transplantation. In this study, we investigated binding interactions between anti-A antibodies and synthetic blood group A trisaccharide conjugated with polyacrylamide of different molecular weights (30 and 1000 kDa). The glycopolymers were equipped with biotin tags and deposited on streptavidin-coated sensor chips. The affinity and kinetics of anti-A antibodies binding to glycoconjugates were studied using surface plasmon resonance (SPR). The high molecular weight conjugate (Atri-PAA(1000)-biotin) enhanced antibody binding capacity by two to three fold compared with the low molecular weight conjugate (Atri-PAA(30)-biotin), whereas varying the carbohydrate content in Atri-PAA(1000)-biotin (20 mol % or 50 mol %) did not affect antibody bindin! g capacity of the glycoconjugate. The obtained results suggest that immunoadsorption devices, especially hollow fiber-based antibody filters which are limited in available surface area for antigen immobilization, may greatly benefit from the new synthetic high molecular weight polyacrylamide glycoconjugates. PMID: 19582848 [PubMed - indexed for MEDLINE] | | |
| [The effects of microenvironment on tissue-engineered osteochondral composite]
January 29, 2010 at 9:29 AM
|
| | [The effects of microenvironment on tissue-engineered osteochondral composite] Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2009 Apr;26(2):433-6 Authors: Li J, Shu Z, Zha Z It is currently reported that extracellular matrix, biological scaffolds, conditions of stress, nutrients and metabolic waste play very important roles in tissue-engineered osteochondral composite. In this paper, we have made a review of their effects on such composite. PMID: 19499819 [PubMed - indexed for MEDLINE] | | | |
No comments:
Post a Comment