bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nociceptive and behavioural sensitisation by protein kinase Cɛ signalling in the CNS
Authors: Van Kolen Kristof , Pullan Shirley , Neefs Jean‐Marc , Dautzenberg Frank M. 
Published: September 2007

AbstractDespite the apparent homology in the protein kinase C (PKC) family, it has become clear that slight structural differences are sufficient to have unique signalling properties for each individual isoform. For PKCɛ in depth investigation of these aspects revealed unique actions in the CNS and lead to development of specific modulators with clinical perspective. In this review, we describe to which extent PKCɛ is distinct from other isoforms on the level of tissue expression and protein structure. As this kinase is highly expressed in the brain, we outline three main aspects of PKCɛ signalling in the CNS. First, its ability to alter the permeability of N‐type Ca2+channels in dorsal root ganglia has been shown to enhance nociception. Secondly, PKCɛ increases anxiety by diminishing GABAAR‐induced inhibitory post‐synaptic currents in the prefrontal cortex. Another important aspect of the latter inhibition is the reduced sensitivity of GABAAreceptors to ethanol, a mechanism potentially contributing to abuse. A third signalling cascade improves cognitive functions by facilitating cholinergic signalling in the hippocampus. Collectively, these findings point to a physical and behavioural sensitising role for this kinase.
Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory
Authors: Wu Chih‐Wei , Chen Yi‐Chieh , Yu Lung , Chen Hsiun‐ing , Jen Chauying J. , Huang A‐Min , Tsai Hsing‐Jung , Chang Ya‐Ting , Kuo Yu‐Min 
Published: September 2007

AbstractNew neurons are continuously generated in hippocampal subgranular zone throughout life, and the amount of neurogenesis is suggested to be correlated with the hippocampus‐dependent function. Several extrinsic stimuli are known to modulate the neurogenesis process. Among them, physical exercise has advantageous effects on neurogenesis and brain function, while inflammation shows the opposite. Herein we showed that a moderate running exercise successfully restored the peripheral lipopolysaccharide (LPS)‐impaired neurogenesis in the dentate area. LPS treatment obstructed neuronal differentiation, but not proliferation. Exercise training facilitated both the proliferation of the neural stem cells and their differentiation into neurons. Interestingly, exercise replenished the LPS‐reduced levels of brain‐derived neurotrophic factor and its receptor, TrkB, and rescued the LPS‐disturbed performance in water maze; while the LPS‐elicited up‐regulation of tumor necrosis factor‐alpha and interleukin‐1β remained unaltered. In conclusion, our findings suggest that running exercise effectively ameliorates the LPS‐disturbed hippocampal neurogenesis and learning and memory performance. Such advantageous effects of running exercise are not due to the alteration of inflammatory response, but possibly by the restoring the LPS‐lessened brain‐derived neurotrophic factor signaling pathway.
Soluble aggregates of the amyloid‐β protein activate endothelial monolayers for adhesion and subsequent transmigration of monocyte cells
Authors: Gonzalez‐Velasquez Francisco J. , Moss Melissa A. 
Published: September 2007

AbstractIncreasing evidence suggests that the deposition of amyloid plaques, composed primarily of the amyloid‐β protein (Aβ), within the cerebrovasculature is a frequent occurrence in Alzheimer’s disease and may play a significant role in disease progression. Accordingly, the pathogenic mechanisms by which Aβ can alter vascular function may have therapeutic implications. Despite observations that Aβ elicits a number of physiological responses in endothelial cells, ranging from alteration of protein expression to cell death, the Aβ species accountable for these responses remains unexplored. In the current study, we show that isolated soluble Aβ aggregation intermediates activate human brain microvascular endothelial cells for both adhesion and subsequent transmigration of monocyte cells in the absence of endothelial cell death and monolayer disruption. In contrast, unaggregated Aβ monomer and mature Aβ fibril fail to induce any change in endothelial adhesion or transmigration. Correlations between average Aβ aggregate size and observed increases in adhesion illustrate that smaller soluble aggregates are more potent activators of endothelium. These results support previous studies demonstrating heightened neuronal activity of soluble Aβ aggregates, including Aβ‐derived diffusible ligands, oligomers, and protofibrils, and further show that soluble aggregates also selectively exhibit activity in a vascular cell model.
PERMANENT GENETIC RESOURCES: Development of microsatellite markers and analysis of their inheritance in the Australian reptile tick, Bothriocroton hydrosauri
Authors: GUZINSKI JARO , SAINT KATHLEEN M. , GARDNER MICHAEL G. , DONNELLAN STEPHEN C. , BULL C. MICHAEL 
Published: September 2007

AbstractDespite long‐term study, the mechanism explaining the parapatric distribution of two Australian reptile tick species is not understood. We describe the development of primers amplifying 10 microsatellite Bothriocroton hydrosauri loci, for the study of population structure and dispersal patterns of this tick. The numbers of alleles per locus ranged from two to seven in ticks from the study site, and the observed heterozygosity between 0.28 and 0.69. Pedigree analysis indicates that one locus is inherited in a non‐Mendelian manner in three families, which was not explained by null allele presence.
PERMANENT GENETIC RESOURCES: Consensus primers of cyp73 genes discriminate willow species and hybrids (Salix, Salicaceae)
Authors: TRUNG LE QUANG , VAN PUYVELDE KAROLIEN , TRIEST LUDWIG 
Published: September 2007

AbstractConsensus primers, based on exon sequences of the cyp73 gene family coding for cinnamate 4‐hydroxylase (C4H) of the lignin biosynthesis pathway, were designed for the tetraploid willow species Salix alba and Salix fragilis. Diagnostic alleles at species level were observed among introns of three cyp73 genes and allowed unambiguous detection of the first generation and introgressed hybrids in populations. Progeny analysis of a female S. alba with a male introgressed hybrid confirmed the codominant inheritance of each intron. Sequences of the diagnostic alleles of both species were similar to those found in the hybrids.
DNA BARCODING: Barcoding corals: limited by interspecific divergence, not intraspecific variation
Authors: SHEARER T. L. , COFFROTH M. A. 
Published: September 2007

AbstractThe expanding use of DNA barcoding as a tool to identify species and assess biodiversity has recently attracted much attention. An attractive aspect of a barcoding method to identify scleractinian species is that it can be utilized on any life stage (larva, juvenile or adult) and is not influenced by phenotypic plasticity unlike morphological methods of species identification. It has been unclear whether the standard DNA barcoding system, based on cytochromecoxidase subunit 1 (COI), is suitable for species identification of scleractinian corals. Levels of intra‐ and interspecific genetic variation of the scleractinian COI gene were investigated to determine whether threshold values could be implemented to discriminate conspecifics from other taxa. Overlap between intraspecific variation and interspecific divergence due to low genetic divergence among species (0% in many cases), rather than high levels of intraspecific variation, resulted in the inability to establish appropriate threshold values specific for scleractinians; thus, it was impossible to discern most scleractinian species using this gene.
Agent‐based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor‐β1
Authors: Mi Qi , Rivière Beatrice , Clermont Gilles , Steed David L. , Vodovotz Yoram 
Published: September 2007

ABSTRACTInflammation and wound healing are inextricably linked and complex processes, and are deranged in the setting of chronic, nonhealing diabetic foot ulcers (DFU). An ideal therapy for DFU should both suppress excessive inflammation while enhancing healing. We reasoned that biological simulation would clarify mechanisms and help refine therapeutic approaches to DFU. We developed an agent‐based model (ABM) capable of reproducing qualitatively much of the literature data on skin wound healing, including changes in relevant cell populations (macrophages, neutrophils, fibroblasts) and their key effector cytokines (tumor necrosis factor‐α [TNF], interleukin [IL]‐1β, IL‐10, and transforming growth factor [TGF]‐β1). In this simulation, a normal healing response results in tissue damage that first increases (due to wound‐induced inflammation) and then decreases as the collagen levels increase. Studies by others suggest that diabetes and DFU are characterized by elevated TNF and reduced TGF‐β1, although which of these changes is a cause and which one is an effect is unclear. Accordingly, we simulated the genesis of DFU in two ways, either by (1) increasing the rate of TNF production fourfold or (2) by decreasing the rate of TGF‐β1 production 67% based on prior literature. Both manipulations resulted in increased inflammation (elevated neutrophils, TNF, and tissue damage) and delayed healing (reduced TGF‐β1 and collagen). Our ABM reproduced the therapeutic effect of platelet‐derived growth factor/platelet releasate treatment as well as DFU debridement. We next simulated the expected effect of administering (1) a neutralizing anti‐TNF antibody, (2) an agent that would increase the activation of endogenous latent TGF‐β1, or (3) latent TGF‐β1 (which has a longer half‐life than active TGF‐β1), and found that these therapies would have similar effects regardless of the initial assumption of the derangement that underlies DFU (elevated TNF vs. reduced TGF‐β1). In silico methods may elucidate mechanisms of and suggest therapies for aberrant skin healing.
Cell suspension cultures of allogenic keratinocytes are efficient carriers for ex vivo gene transfer and accelerate the healing of full‐thickness skin wounds by overexpression of human epidermal growth factor
Authors: Vranckx Jan Jeroen , Hoeller Daniela , Velander Patrik E. M. , Theopold Christoph F. P. , Petrie Nicola , Takedo Akira , Eriksson Elof , Yao Feng 
Published: September 2007

ABSTRACTThe concept of using growth factor therapy to induce wound repair has been endorsed in studies that show reduced growth factors in wound fluid from chronic and aged wounds. In this study, we used cell suspensions of allogenic keratinocytes as gene‐delivery vehicles for human epidermal growth factor (hEGF) and analyzed their impact on wound repair in a porcine wound‐healing model. Full‐thickness wounds were created on the backs of six Yorkshire pigs and covered with a wound chamber to create a wet wound‐healing environment. First, 5 × 105 allogenic, autogenic, or mixed keratinocytes were transplanted into wounds and healing parameters were analyzed. Second, we measured long‐term reepithelialization and contraction rates from day 8 until day 35. In the third experiment, allogenic keratinocytes were transfected with an hEGF‐expressing plasmid pCEP‐hEGF and transplanted in full‐thickness wounds to improve repair. Wounds treated with autogenic, allogenic, or mixed keratinocytes showed a significantly higher rate of reepithelialization relative to saline‐treated control wounds. Repetitive biopsies indicated that the use of allogenic keratinocytes did not lead to long‐term wound breakdown. Wounds treated with hEGF‐expressing allogenic keratinocytes reepithelialized faster than wounds treated with allogenic keratinocytes or control wounds. With a peak hEGF expression of 920.8 pg/mL, hEGF was detectable until day 5 after transplantation compared with minimal hEGF expression in control wounds. This study shows that allogenic keratinocytes can serve as efficient gene transfer vehicles for ex vivo growth factor delivery to full‐thickness wounds and overexpression of hEGF further improves reepithelialization rates.
db/db mice exhibit severe wound‐healing impairments compared with other murine diabetic strains in a silicone‐splinted excisional wound model
Authors: Michaels Joseph , Churgin Samara S. , Blechman Keith M. , Greives Matthew R. , Aarabi Shahram , Galiano Robert D. , Gurtner Geoffrey C. 
Published: September 2007

ABSTRACTThe pathophysiology of diabetic wound healing and the identification of new agents to improve clinical outcomes continue to be areas of intense research. There currently exist more than 10 different murine models of diabetes. The degree to which wound healing is impaired in these different mouse models has never been directly compared. We determined whether differences in wound impairment exist between diabetic models in order to elucidate which model would be the best to evaluate new treatment strategies. Three well‐accepted mouse models of diabetes were used in this study: db/db, Akita, and streptozocin (STZ)‐induced C57BL/6J. Using an excisional model of wound healing, we demonstrated that db/db mice exhibit severe impairments in wound healing compared with STZ and Akita mice. Excisional wounds in db/db mice show a statistically significant delay in wound closure, decreased granulation tissue formation, decreased wound bed vascularity, and markedly diminished proliferation compared with STZ, Akita, and control mice. There was no difference in the rate of epithelialization of the full‐thickness wounds between the diabetic or control mice. Our results suggest that splinted db/db mice may be the most appropriate model for studying diabetic wound‐healing interventions as they demonstrate the most significant impairment in wound healing. This study utilized a novel model of wound healing developed in our laboratory that stents wounds open using silicone splints to minimize the effects of wound contraction. As such, it was not possible to directly compare the results of this study with other studies that did not use this wound model.
Effects of decreased insulin‐like growth factor‐1 stimulation on hypoxia inducible factor 1‐α protein synthesis and function during cutaneous repair in diabetic mice
Authors: Yu Diana H. , Mace Kimberly A. , Hansen Scott L. , Boudreau Nancy , Young David M. 
Published: September 2007

ABSTRACTInsulin‐like growth factor‐1 (Igf‐1), a critical mediator of tissue repair, is significantly decreased in diabetic wounds. Furthermore, decreased levels of hypoxia‐inducible factor 1‐α (Hif‐1α) and its target genes are also associated with impaired wound healing in diabetic mice. The aim of our study was to examine whether the reduced levels of Igf‐1 are responsible for the reduction in Hif‐1α protein synthesis and activity in diabetic wounds. We provide evidence that Igf‐1 regulates Hif‐1α protein synthesis and activity during wound repair. In addition, Igf‐1 stimulated phosphytidylinositol 3‐kinase activity in diabetic fibroblasts, which, in turn, increased activation of the translational regulatory protein, p70 S6 kinase. Moreover, improved healing of diabetic wounds by addition of recombinant IGF‐1 protein was associated with an increase in Hif‐1α protein synthesis and function in vivo.
Enhancement of keratinocyte performance in the production of tissue‐engineered skin using a low‐calcium medium
Authors: Hernon Catherine A. , Harrison Caroline A. , Thornton Daniel J. A. , MacNeil Sheila 
Published: September 2007

ABSTRACTThe success of laboratory‐expanded autologous keratinocytes for the treatment of severe burn injuries is often compromised by their lack of dermal remnants and failure to establish a secure dermo‐epidermal junction on the wound bed. We have developed a tissue‐engineered skin substitute for in vivo use, based on a sterilized donor human dermis seeded with autologous keratinocytes and fibroblasts. However, culture rates are currently too slow for clinical use in acute burns. Our aim in this study was to increase the rate of production of tissue‐engineered skin. Two approaches were explored: one using a commercial low‐calcium media and the other supplementing well‐established media for keratinocyte culture with the calcium‐chelating agent ethylene glutamine tetra‐acetic acid (EGTA). Using commercial low‐calcium media for both the initial cell culture and subsequent culture of tissue‐engineered skin did not produce tissue suitable for clinical use. However, it was possible to enhance the initial proliferation of keratinocytes and to increase their horizontal migration in tissue‐engineered skin by supplementing established culture medium with 0.04 mM EGTA without sacrificing epidermal attachment and differentiation. Enhancement of keratinocyte migration with EGTA was also maximal in the absence of fibroblasts or basement membrane.
Increased apoptosis at the late stage of tendon healing
Authors: Lui Pauline Po Yee , Cheuk Yau Chuk , Hung Leung Kim , Fu Sai Chuen , Chan Kai Ming 
Published: September 2007

ABSTRACTThe mechanism for the clearance of excess healing fibroblasts at the end of tendon healing has not been reported despite the importance of maintaining tissue homeostasis. This study investigated the role of apoptosis in cell turnover in a rat central 1/3 patellar tendon donor site injury model. At days 4, 7, 14, 28, months 2 and 6, the rats were killed. Patellar tendons without injury served as control. Apoptotic cells were determined by an in situ terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labeling (TUNEL) assay and anti‐active caspase‐3 antibodies, while proliferating cells were determined by anti‐proliferating cell nuclear antigen antibodies. The total fibroblast‐like cell density in the center of the wound increased from day 4 and thereafter steadily returned to normal. In situ TUNEL assay showed few positive staining cells in the wound at days 4 and 7. The percentages of TUNEL‐positive fibroblast‐like cells showing morphological characteristics of apoptosis increased sharply and reached the maximum on day 28 (median %: 31.38%). No fibroblast‐like cell was stained at month 6 and the healed tissue was similar to that in a normal uninjured tendon. A similar trend was observed with active caspase‐3 immunohistochemistry. In conclusion, an increase in apoptosis at the end of tendon healing coincided with a decrease in cellularity.
Stromal progenitor cell therapy corrects the wound‐healing defect in the ischemic rabbit ear model of chronic wound repair
Authors: Volk Susan W. , Radu Antoneta , Zhang Liping , Liechty Kenneth W. 
Published: September 2007

ABSTRACTChronic wounds create a formidable clinical problem resulting in considerable morbidity and healthcare expenditure. The etiology for wound healing impairment appears to be multifactorial; however, ischemia is a common factor in most types of chronic wounds. Ideal therapy for such wounds would be to correct deficiencies in growth factors and matrix components and provide cellular precursors required for timely wound closure. We hypothesized that stromal progenitor cell (SPC) therapy could correct the ischemic wound‐healing defect through both direct and indirect mechanisms. To test this hypothesis, we used the ischemic rabbit ear model of chronic wound healing. We found that treatment of the wounds with SPCs was able to reverse the ischemic wound‐healing impairment, with improved granulation tissue formation and reepithelialization compared with vehicle or bone marrow mononuclear cell controls. In vitro, SPCs were found to produce factors involved in angiogenesis and reepithelialization, and extracellular matrix components, providing evidence for both direct and indirect mechanisms for the observed correction of the healing impairment in these wounds. Treatment of ischemic wounds with SPCs can dramatically improve wound healing and provides a rationale for further studies focused on SPCs as a potential cellular therapy in impaired wound healing.
Sustained expression of Hif‐1α in the diabetic environment promotes angiogenesis and cutaneous wound repair
Authors: Mace Kimberly A. , Yu Diana H. , Paydar Keyianoosh Z. , Boudreau Nancy , Young David M. 
Published: September 2007

ABSTRACTImpaired wound healing in diabetic patients is associated with deficiencies in the production of factors involved in cell proliferation and migration, such as vascular endothelial growth factor. However, it remains unclear how the transcriptional regulation of the genes encoding these factors is affected by the diabetic environment. Hypoxia‐inducible factor‐1α (Hif‐1α), the regulatory subunit of the Hif‐1 transcription factor, plays an important role in activating many of these genes. Therefore, we tested whether Hif‐1α function is impaired in the diabetic wound environment and whether restoring Hif‐1 function improves wound healing. Here, we show that Hif‐1α protein levels are dramatically reduced in wounds of leptin receptor‐deficient diabetic mice compared with nondiabetic littermates. Reduction in Hif‐1α levels results in decreased DNA‐binding activity and in decreased expression of several Hif‐1 target genes, including vascular endothelial growth factor, heme oxygenase‐1, and inducible nitric oxide synthase. Furthermore, we demonstrate that sustained expression of Hif‐1α in leptin receptor‐deficient diabetic wounds restores expression of these factors, enhances angiogenesis, and significantly accelerates wound healing. Taken together, these results suggest that Hif‐1α function plays a significant role in wound healing and reduced levels of Hif‐1α may contribute to impaired healing.
Influence of papain urea copper chlorophyllin on wound matrix remodeling
Authors: Telgenhoff Dale , Lam Kan , Ramsay Sarah , Vasquez Valerie , Villareal Kristine , Slusarewicz Paul , Attar Paul , Shroot Braham 
Published: September 2007

ABSTRACTThe purpose of this study was to examine the dermal and epidermal alterations associated with wound healing in wounds treated with papain urea copper chlorophyllin (PUC), papain‐urea, copper chlorophyllin, or urea base ointment and compare these with moist wound care using a porcine full‐thickness infected wound model. All the wounds were evaluated postsurgery for erythema, transepidermal water loss, microscopic morphology, and changes in protein expression. Examination of stained paraffin sections revealed an increase in the number of keratinocytes present in the epidermis of the PUC and papain‐treated pigs, relative to moist control. This increase in keratinocyte number corresponded to an increase in the movement of the keratinocytes into the underlying dermis in the form of rete pegs. In the dermis, there appeared to be an increase in blood vessel formation, collagen I deposition, and mature collagen in the papain and PUC treated tissues. The quality of healing appears to be enhanced based on the number of keratinocytes present in the epidermis, the extensive rete peg formation, the increase in vasculature, and the increase in collagen birefringence.