Biologically aware lighting for newborn intensive care.

Objective: We designed and implemented a novel neonatal intensive care (NICU) lighting system to support the current understanding of daylight-coupled physiology.

Methods: We created a system that generates wavelengths corresponding to the known blue and violet activation spectra of non-visual opsins. These are known to mediate energy management and related physiologic activity.

Biologically Aware Lighting for Newborn Intensive Care.

Objective: We designed and implemented a novel neonatal intensive care (NICU) lighting system to support current understanding of sunlight-coupled physiology.

Methods: We created a system that generates wavelengths corresponding to the known blue and violet activation spectra of non-visual opsins. These are known to mediate energy management and related physiologic activity.

Red Light Mitigates the Deteriorating Placental Extracellular Matrix in Late Onset of Preeclampsia and Improves the Trophoblast Behavior.

Preeclampsia is a serious pregnancy disorder which in extreme cases may lead to maternal and fetal injury or death. Preexisting conditions which increase oxidative stress, e.g.

Non-thermal Infrared Light Treatment of Ischemia/Reperfusion Injury and Subsequent Analysis of Macrophage Differentiation.

Tissue damage and necrosis from inflammatory processes are a consequence of ischemia reperfusion injury (IRI). In skeletal muscle, ischemia reduces the aerobic energy capacity of muscle cells, leading to adverse biochemical alterations and inflammation. The goal of this study is to show that exposure to near-infrared light (NIR) during a period of ischemia reduces IRI by decreasing necrosis and inflammation in addition to decreasing proinflammatory M1 and increasing protective M2 macrophages.

Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos.

Primary cilia are ubiquitous microtubule-based organelles that serve as signaling hubs for numerous developmental pathways, most notably the Hedgehog (Hh) pathway. Defects in the structure or function of primary cilia result in a class of diseases called ciliopathies. It is well known that primary cilia participate in transducing a Hh signal, and as such ciliopathies frequently present with phenotypes indicative of aberrant Hh function.

Inhibition of myeloperoxidase increases revascularization and improves blood flow in a diabetic mouse model of hindlimb ischaemia.

Objective: Diabetes mellitus is a significant risk factor for peripheral artery disease. Diabetes mellitus induces chronic states of oxidative stress and vascular inflammation that increase neutrophil activation and release of myeloperoxidase. The goal of this study is to determine whether inhibiting myeloperoxidase reduces oxidative stress and neutrophil infiltration, increases vascularization, and improves blood flow in a diabetic murine model of hindlimb ischaemia.

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice.

The interferon regulatory factor 5 (IRF5) is crucial for cells to determine if they respond in a pro-inflammatory or anti-inflammatory fashion. IRF5's ability to switch cells from one pathway to another is highly attractive as a therapeutic target. We designed a decoy peptide IRF5D with a molecular modeling software for designing small molecules and peptides.

A tissue-specific role for intraflagellar transport genes during craniofacial development.

Primary cilia are nearly ubiquitous, cellular projections that function to transduce molecular signals during development. Loss of functional primary cilia has a particularly profound effect on the developing craniofacial complex, causing several anomalies including craniosynostosis, micrognathia, midfacial dysplasia, cleft lip/palate and oral/dental defects. Development of the craniofacial complex is an intricate process that requires interactions between several different tissues including neural crest cells, neuroectoderm and surface ectoderm.

Unique spatiotemporal requirements for intraflagellar transport genes during forebrain development.

Primary cilia are organelles extended from virtually all cells and are required for the proper regulation of a number of canonical developmental pathways. The role in cortical development of proteins important for ciliary form and function is a relatively understudied area. Here we have taken a genetic approach to define the role in forebrain development of three intraflagellar transport proteins known to be important for primary cilia function.

Intraocular pressure in the smallest primate aging model: the gray mouse lemur.

Objective: The aim of this study was to assess the practicability of common tonometers used in veterinary medicine for rapid intraocular pressure (IOP) screening, to calibrate IOP values gained by the tonometers, and to define a reference IOP value for the healthy eye in a new primate model for aging research, the gray mouse lemur.

Studied Animals And Procedures: TonoVet and the TonoPen measurements were calibrated manometrically in healthy enucleated eyes of mouse lemurs euthanized for veterinary reasons. For comparison of the practicability of both tonometers as a rapid IOP assessment tool for living mouse lemurs, the IOP of 24 eyes of 12 animals held in the hand was measured.

Brg1 directly regulates Olig2 transcription and is required for oligodendrocyte progenitor cell specification.

The Olig2 basic-helix-loop-helix transcription factor promotes oligodendrocyte specification in early neural progenitor cells (NPCs), including radial glial cells, in part by recruiting SWI/SNF chromatin remodeling complexes to the enhancers of genes involved in oligodendrocyte differentiation. How Olig2 expression is regulated during oligodendrogliogenesis is not clear. Here, we find that the Brg1 subunit of SWI/SNF complexes interacts with a proximal Olig2 promoter and represses Olig2 transcription in the mouse cortex at E14, when oligodendrocyte progenitors (OPCs) are not yet found in this location.

An IRF5 Decoy Peptide Reduces Myocardial Inflammation and Fibrosis and Improves Endothelial Cell Function in Tight-Skin Mice.

Interferon regulatory factor 5 (IRF5) has been called a "master switch" for its ability to determine whether cells mount proinflammatory or anti-inflammatory responses. Accordingly, IRF5 should be an attractive target for therapeutic drug development. Here we report on the development of a novel decoy peptide inhibitor of IRF5 that decreases myocardial inflammation and improves vascular endothelial cell (EC) function in tight-skin (Tsk/+) mice.

Using the avian mutant talpid2 as a disease model for understanding the oral-facial phenotypes of oral-facial-digital syndrome.

Oral-facial-digital syndrome (OFD) is a ciliopathy that is characterized by oral-facial abnormalities, including cleft lip and/or palate, broad nasal root, dental anomalies, micrognathia and glossal defects. In addition, these individuals have several other characteristic abnormalities that are typical of a ciliopathy, including polysyndactyly, polycystic kidneys and hypoplasia of the cerebellum. Recently, a subset of OFD cases in humans has been linked to mutations in the centriolar protein C2 Ca(2+)-dependent domain-containing 3 (C2CD3).

Porous ongrowth surfaces alter osteoblast maturation and mineralization.

Implant fixation through osseointegration is essential for the success of uncemented total joint arthroplasty, and nature and composition of implant surface play a critical role in this process. Despite widespread use of uncemented implants, the extent of bone ingrowth into implants is generally only a small percentage of the total implant surface. An understanding of the processes whereby bone cells grow into and multiply on porous surfaces is critical for the design and manufacture of implants that maximize ingrowth and implant fixation.

Metal ions activate vascular endothelial cells and increase lymphocyte chemotaxis and binding.

Metal on metal articulations in hip arthroplasty offer advantages, including lower volumetric wear compared to conventional metalonpolyethylene bearings, and increased resistance to dislocation. Reports described early failures, with histologic features similar to a Type IV immune response. Mechanisms by which metal wear products cause this reaction are not completely understood.

Digestion products of the PH20 hyaluronidase inhibit remyelination.

Objective: Oligodendrocyte progenitor cells (OPCs) recruited to demyelinating lesions often fail to mature into oligodendrocytes (OLs) that remyelinate spared axons. The glycosaminoglycan hyaluronan (HA) accumulates in demyelinating lesions and has been implicated in the failure of OPC maturation and remyelination. We tested the hypothesis that OPCs in demyelinating lesions express a specific hyaluronidase, and that digestion products of this enzyme inhibit OPC maturation.

Transient repetitive exposure to low level light therapy enhances collateral blood vessel growth in the ischemic hindlimb of the tight skin mouse.

The tight skin mouse (Tsk(-/+)) is a model of scleroderma characterized by impaired vasoreactivity, increased oxidative stress, attenuated angiogenic response to VEGF and production of the angiogenesis inhibitor angiostatin. Low-level light therapy (LLLT) stimulates angiogenesis in myocardial infarction and chemotherapy-induced mucositis. We hypothesize that repetitive LLLT restores vessel growth in the ischemic hindlimb of Tsk(-/+) mice by attenuating angiostatin and enhancing angiomotin effects in vivo.

Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants.

Objective: The major form of magnetic resonance imaging-defined white matter injury (WMI) comprises diffuse lesions where the burden of small necrotic foci (microscopic necrosis) is poorly defined. We hypothesized that myelination failure associated with diffuse WMI involves an aberrant injury response linked to arrested preoligodendrocyte (preOL) maturation in reactive astrocyte-rich lesions.

Methods: A retrospective autopsy series (1983-2000) was selected for cases with diffuse WMI and analyzed relative to prospectively collected contemporary cases (2003-2010).

Astrocytes in aged nonhuman primate brain gray matter synthesize excess hyaluronan.

The glycosaminoglycan hyaluronan (HA) accumulates in central nervous system lesions where it limits astrogliosis but also inhibits oligodendrocyte progenitor cell (OPC) maturation. The role of hyaluronan in normative brain aging has not been previously investigated. Here, we tested the hypothesis that HA accumulates in the aging nonhuman primate brain.

Abnormal fibrillin-1 expression and chronic oxidative stress mediate endothelial mesenchymal transition in a murine model of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by oxidative stress, impaired vascular function, and attenuated angiogenesis. The tight-skin (Tsk(-/+)) mouse is a model of SSc that displays many of the cellular features of the clinical disease. We tested the hypotheses that abnormal fibrillin-1 expression and chronic phospholipid oxidation occur in Tsk(-/+) mice and, furthermore, that these factors precipitate a prooxidant state, collagen-related protein expression, apoptosis, and mesenchymal transition in endothelial cells cultured on Tsk(-/+) extracellular matrix.

Lost in space? Searching for directions in the spatial modelling of individuals, populations and species ranges.

The workshop 'Spatial models in animal ecology, management and conservation' held at Silwood Park (UK), 9-11 March 2010, aimed to synthesize recent progress in modelling the spatial dynamics of individuals, populations and species ranges and to provide directions for research. It brought together marine and terrestrial researchers working on spatial models at different levels of organization, using empirical as well as theory-driven approaches. Different approaches, temporal and spatial scales, and practical constraints predominate at different levels of organization and in different environments.

Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury.

Objective: Abnormal myelination is a major pathological sequela of chronic periventricular white matter injury in survivors of premature birth. We tested the hypothesis that myelination failure in chronic hypoxia-ischemia-induced periventricular white matter injury is related to persistent depletion of the oligodendrocyte (OL) precursor pool required to generate mature myelinating OLs.

Methods: A neonatal rat model of hypoxia-ischemia was used where acute degeneration of late OL progenitors (preOLs) occurs via a mostly caspase-independent mechanism.

Long term clinical trials: how much information do participants retain from the informed consent process?

Previous studies report mixed results about how much information study participants actually can read, understand and retain after completing the informed consent process; fewer studies have examined disparities in the retention and recall of information by patient factors, such as age, education, and race. Not retaining or being able to recall information from the informed consent process has potentially important ethical and legal implications and consequences for research quality and integrity, especially when found in populations that commonly are underserved or underrepresented in clinical trials. To determine how much basic knowledge participants finishing a five-year, multi-center, double-blinded randomized, placebo-controlled clinical trial had about the study, participants (n=1,789) were asked at their final follow-up visit three multiple-choice questions: (1) the study's purpose; (2) the name of the medication under investigation; (3) the main side effect of the medication.

Brg1 is required for murine neural stem cell maintenance and gliogenesis.

Epigenetic alterations in cell-type-specific gene expression control the transition of neural stem cells (NSCs) from predominantly neurogenic to predominantly gliogenic phases of differentiation, but how this switch occurs is unclear. Here, we show that brahma-related gene 1 (Brg1), an ATP-dependent chromatin remodeling factor, is required for the repression of neuronal commitment and the maintenance of NSCs in a state that permits them to respond to gliogenic signals. Loss of Brg1 in NSCs in conditional brg1 mutant mice results in precocious neuronal differentiation, such that cells in the ventricular zone differentiate into post-mitotic neurons before the onset of gliogenesis.