bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARG3.1/ARC expression in hippocampal dentate gyrus astrocytes: ultrastructural evidence and co‐localization with glial fibrillary acidic protein
Authors: Rodríguez J. J. , Davies H. A. , Errington M. L. , Verkhratsky A. , Bliss T. V. P. , Stewart M. G. 
Published: April 2008

AbstractSynaptic efficacy following long‐term potentiation (LTP) and memory consolidation is associated with changes in the expression of immediate early genes (IEGs). These changes are often accompanied by increased expression of glial fibrillary acidic protein (GFAP). While the protein products of the majority of IEGs are mainly restricted to the cell body, Arg3.1/Arc product is rapidly delivered to dendrites, where it accumulates close to synaptic sites. Arg3.1/Arc protein was originally considered neurone specific; however, we have recently found Arg3.1/Arc immunoreactivity (Arg3.1/Arc‐IR) within glial cells and demonstrated its increased expression after LTP in the hippocampal dentate gyrus (DG). Here, we have further investigated this novel finding, using electron microscopic immunocytochemistry to determine the localization and sub‐cellular distribution of Arg3.1/Arc protein in GFAP positive glia (GFAP‐IR) in the DG. Arg3.1/Arc labelling was seen prominently in GFAP‐IR glial cell bodies and in large‐ and medium‐sized glial filamentous processes. GFAP‐labelled medium–small peri‐synaptic glial profiles also displayed Arg3.1/Arc‐IR; however, the very thin and distal glial filaments only displayed Arc‐IR. Arc‐IR was distributed throughout the cytoplasm, often associated with GFAP filaments, and along the plasma membrane of glial processes. Peri‐synaptic glial Arg3.1/Arc‐IR processes were apposed to pre‐ and/or post‐synaptic profiles at asymmetric axospinous synapses. These data, taken with our earlier study which provided evidence for an increase in astrocytic Arg3.1/Arc‐IR after the induction of LTP, suggest a role for glial Arg3.1/Arc in structural and synaptic plasticity which may be critical for the maintenance of cognitive functions.
Consequences of altered eicosanoid patterns for nociceptive processing in mPGES‐1‐deficient mice
Authors: Brenneis Christian , Coste Ovidiu , Schmidt Ronald , Angioni Carlo , Popp Laura , Nusing Rolf M. , Becker Wiebke , Scholich Klaus , Geisslinger Gerd 
Published: April 2008

AbstractCyclooxygenase‐2 (COX‐2)‐dependent prostaglandin (PG) E2synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2synthase‐1 (mPGES‐1) isomerizes COX‐2‐derived PGH2to PGE2. Here, we evaluated the effect of mPGES‐1‐deficiency on the noci‐ceptive behavior in various models of nociception that depend on PGE2synthesis. Surprisingly, in the COX‐2‐dependent zymosan‐evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES‐1‐deficient mice despite a marked decrease of the spinal PGE2synthesis. Similarly, the nociceptive behavior was unaltered in mPGES‐1‐deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES‐1‐deficient mice showed a redirection of the PGE2synthesis to PGD2, PGF2αand 6‐keto‐PGF1α(stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci‐ception they may compensate the loss of PGE2synthesis in mPGES‐1‐deficient mice.
Pro‐inflammatory effects of hydrogen sulphide on substance P in caerulein‐induced acute pancreatitis
Authors: Bhatia Madhav , Sidhapuriwala Jenab N. , Wei Ng Siaw , Tamizhselvi Ramasamy , Moochhala Shabbir M. 
Published: April 2008

AbstractHydrogen sulphide (H2S), a novel gasotransmitter, has been recognized to play an important role in inflammation. Cystathionine‐γ‐lyase (CSE) is a major H2S synthesizing enzyme in the cardiovascular system and DL‐propargylglycine (PAG) is an irreversible inhibitor of CSE. Substance P (SP), a product of preprotachykinin‐A (PPT‐A) gene, is a well‐known pro‐inflammatory mediator which acts principally through the neurokinin‐1 receptor (NK‐1R). We have shown an association between H2S and SP in pulmonary inflammation as well as a pro‐inflammatory role of H2S and SP in acute pancreatitis. The present study was aimed to investigate the interplay between pro‐inflammatory effects of H2S and SP in a murine model of caerulein‐induced acute pancreatitis. Acute pancreatitis was induced in mice by 10 hourly intraperitoneal injections of caerulein (50 (g/kg). PAG (100 mg/kg, i.p.) was administered either 1 hr before (prophylactic) or 1 hr after (therapeutic) the first caerulein injection. PAG, given prophylactically as well as therapeutically, significantly reduced plasma H2S levels and pancreatic H2S synthesizing activities as well as SP concentrations in plasma, pancreas and lung compared with caerulein‐induced acute pancreatitis. Furthermore, prophylactic as well as therapeutic administration of PAG significantly reduced PPT‐A mRNA expression and NK‐1R mRNA expression in both pancreas and lung when compared with caerulein‐induced acute pancreatitis. These results suggest that the pro‐inflammatory effects of H2S may be mediated by SP‐NK‐1R pathway in acute pancreatitis.
Opposite effects of uracil and adenine nucleotides on the survival of murine cardiomyocytes
Authors: Mazzola Alessia , Amoruso Emanuela , Beltrami Elena , Lecca Davide , Ferrario Silvia , Cosentino Simona , Tremoli Elena , Ceruti Stefania , Abbracchio Maria P. 
Published: April 2008

AbstractWe previously showed that the human heart expresses all known P2X and P2Y receptors activated by extra‐cellular adenine or uracil nucleotides. Despite evidence that, both in humans and rodents, plasma levels of ATP and UTP markedly increase during myocardial infarction, the differential effects mediated by the various adenine‐ and uracil‐preferring myocardial P2 receptors are still largely unknown. Here, we studied the effects of adenine and uracil nucleotides on murine HL‐1 cardiomyocytes. RT‐PCR analysis showed that HL‐1 cardiomyocytes express all known P2X receptors (except for P2X2), as well as the P2Y2,4,6,14subtypes. Exposure of cardiomyocytes to adenine nucleotides (ATP, ADP or BzATP) induced apoptosis and necrosis, as determined by flow‐cytometry. Cell death was exacerbated by tumour necrosis factor (TNF)‐α, a cytokine implicated in chronic heart failure progression. Conversely, uracil nucleotides (UTP, UDP and UDPglucose) had no effect ‘per se’, but fully counteracted the deleterious effects induced by adenine nucleotides and TNF‐α, even if added to cardiomyocytes after beginning exposure to these cell death‐inducing agents. Thus, exposure of cardiomyocytes to elevated concentrations of ATP or ADP in the presence of TNF‐α contributes to cell death, an effect which is counteracted by uracil‐preferring P2 receptors. Cardiomyocytes do not need to be ‘primed’ by uracil nucleotides to become insensitive to adenine nucleotides‐induced death, suggesting the existence of a possible ‘therapeutic’ window for uracil nucleotides‐mediated protection. Thus, release of UTP during cardiac ischaemia and in chronic heart failure may protect against myocardial damage, setting the basis for developing novel cardioprotective agents that specifically target uracil‐preferring P2Y receptors.
Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy
Authors: Docheva Denitsa , Padula Daniela , Popov Cvetan , Mutschler Wolf , Clausen‐Schaumann Hauke , Schieker Matthias 
Published: April 2008

AbstractWithin the bone lie several different cell types, including osteoblasts (OBs) and mesenchymal stem cells (MSCs). The MSCs are ideal targets for regenerative medicine of bone due to their differentiation potential towards OBs. Human MSCs exhibit two distinct morphologies: rapidly self‐renewing cells (RS) and flat cells (FC) with very low proliferation rates. Another cell type found in pathological bone conditions is osteosarcoma. In this study, we compared the topographic and morphometric features of RS and FC cells, human OBs and MG63 osteosarcoma cells by atomic force microscopy (AFM). The results demonstrated clear differences: FC and hOB cells showed similar ruffled topography, whereas RS and MG63 cells exhibited smoother surfaces. Furthermore, we investigated how selected substrates influence cell morphometry. We found that RS and MG63 cells were flatter on fibrous substrates such as polystyrene and collagen I, but much more rounded on glass, the smoothest surface. In contrast, cells with large area, namely FC and hOB cells, did not exhibit pronounced changes in flatness with regards to the different substrates. They were, however, remarkably flatter in comparison to RS and MG63 cells. We could explain the differences in flatness by the extent of adhesion. Indeed, FC and hOB cells showed much higher content of focal adhesions. Finally, we used the AFM to determine the cellular Young's modulus. RS, FC and hOB cells showed comparable stiffness on the three different substrates, while MG63 cells demonstrated the unique feature of increased elasticity on collagen I. In summary, our results show, for the first time, a direct comparison between the morphometric and biophysical features of different human cell types derived from normal and pathological bone. Our study manifests the opinion that along with RNA, proteomic and functional research, morphological and biomechanical characterization of cells also reveals novel cell features and interrelationships.
The unfolded protein response in hereditary haemochromatosis
Authors: De Almeida S.F. , De Sousa M. 
Published: April 2008

AbstractTo cope with the accumulation of unfolded or misfolded proteins the endoplasmic reticulum (ER) has evolved specific signalling pathways collectively called the unfolded protein response (UPR). Elucidation of the mechanisms governing ER stress signallinghas linked this response to the regulation of diverse physiologic processes as well as to the progression of a number of diseases. Interest in hereditary haemochromatosis (HH) has focused on the study of proteins implicated in iron homeostasis and on the identification of new alleles related with the disease. HFE has been amongst the preferred targets of interest, since the discovery that its C282Y mutation was associated with HH. However, the discrepancies between the disease penetrance and the frequency of this mutation have raised the possibility that its contribution to disease progression might go beyond the mere involvement in regulation of cellular iron uptake. Recent findings revealed that activation of the UPR is a feature of HH and that this stress response may be involved in the genesis of immunological anomalies associated with the disease. This review addresses the connection of the UPR with HH, including its role in MHC‐I antigen presentation pathway and possible implications for new clinical approaches to HH.
The functions and possible significance of Kremen as the gatekeeper of Wnt signalling in development and pathology
Authors: Nakamura T , Nakamura T , Matsumoto K 
Published: April 2008

Introduction
Identification and structure of Krm
Krm as a negative regulator in Wnt signalling
Expression of Krm
Krm in development
Wnt signalling in stem cell regulation and diseases
Wnt signalling, Krm and cancer
Perspectives

AbstractKremen (Krm) was originally discovered as a novel transmembrane protein containing the kringle domain. Both Krm1 (the first identified Krm) and its relative Krm2 were later identified to be the high‐affinity receptors for Dickkopf (Dkk), the inhibitor of Wnt/β‐catenin signalling. The formation of a ternary complex composed of Krm, Dkk, and Lrp5/6 (the coreceptor of Wnt) inhibits Wnt/β‐catenin signalling. In Xenopus gastrula embryos, Wnt/β‐catenin signalling regulates anterior‐posterior patterning, with low‐signalling in anterior regions. Inhibition of Krm1/2 induces embryonic head defects. Together with anterior localization of Krms and Dkks, the inhibition of Wnt signalling by Dkk‐Krm action seems to allow anterior embryonic development. During mammalian development, krm1 mRNA expression is low in the early stages, but gradually and continuously increases with developmental progression and differentiation. In contrast with the wide, strong expression of krm1 mRNA in mature tissues, expression of krm1 is diminished in a variety of human tumor cells. Since stem cells and undifferentiated cells rely on Wnt/β‐catenin signalling for maintenance in a low differentiation state, the physiological shutdown of Wnt/β‐catenin signalling by Dkk‐Krm is likely to set cells on a divergent path toward differentiation. In tumour cells, a deficit of Krm may increase the susceptibility to tumourigenic transformation. Both positive and negative regulation of Wnt/β‐catenin signalling definitively contributes to diverse developmental and physiological processes, including cell‐fate determination, tissue patterning and stem cell regulation. Krm is quite significant in these processes as the gatekeeper of the Wnt/β‐catenin signalling pathway.
Histology far away from Flatland: 3D roller‐coasting into grade‐dependent angiogenetic patterns in oligodendrogliomas
Authors: Cassoni P. , Gaetano L. , Senetta R. , Bussolati B. , Molinaro L. , Bussolati G. 
Published: April 2008

AbstractAngiogenesis plays a key role in tumour progression, and undergoes structural changes associated to tumour biology itself. Although vessel density can be easily evaluated in brain tumours using a traditional immuno‐histochemical approach, other parameters of conceptual/biological interest, such as the complex patterns of vascular growth, cannot be fully understood using a traditional bi‐dimensional evaluation. We use here surgical specimens derived from oligodendrogliomas as a model for a novel elucidative 3D reconstruction of the grade‐dependent vascular arborisation in brain tumours.
Neural stem cells, inflammation and NF‐κB: basic principle of maintenance and repair or origin of brain tumours?
Authors: Widera D. , Kaus A. , Kaltschmidt C. , Kaltschmidt B. 
Published: April 2008

Neural Stem Cells
Inflammation, NF‐κB and neural stem cells
Inflammation, NF‐κB and cancer
NSCs and brain cancer
NF‐κB target genes affecting NSCs and tumour formation
Conclusion

AbstractSeveral recent reports suggest that inflammatory signals play a decisive role in the self‐renewal, migration and differentiation of multipotent neural stem cells (NSCs). NSCs are believed to be able to ameliorate the symptoms of several brain pathologies through proliferation, migration into the area of the lesion and either differentiation into the appropriate cell type or secretion of anti‐inflammatory cytokines. Although NSCs have beneficial roles, current evidence indicates that brain tumours, such as astrogliomas or ependymomas are also caused by tumour‐initiating cells with stem‐like properties. However, little is known about the cellular and molecular processes potentially generating tumours from NSCs. Most pro‐inflammatory conditions are considered to activate the transcription factor NF‐κB in various cell types. Strong inductive effects of NF‐κB on proliferation and migration of NSCs have been described. Moreover, NF‐κB is constitutively active in most tumour cells described so far. Chronic inflammation is also known to initiate cancer. Thus, NF‐κB might provide a novel mechanistic link between chronic inflammation, stem cells and cancer. This review discusses the apparently ambivalent role of NF‐κB: physiological maintenance and repair of the brain via NSCs, and a potential role in tumour initiation. Furthermore, it reveals a possible mechanism of brain tumour formation based on inflammation and NF‐κB activity in NSCs.
Molecular mechanism of regulation of the calcium‐binding protein calbindin‐D9k,and its physiological role(s) in mammals: a review of current research
Authors: Choi Kyung‐Chul , Jeung Eui‐Bae 
Published: April 2008

IntroductionPhenotype ofCaBP‐9kknockout mouseUterine expression and regulation of CaBP‐9kPlacental expression and regulation ofCaBP‐9kDuodenal and renal expression and regulation of CaBP‐9kPituitary expression and regulation of CaBP‐9kTranscriptional regulation of CaBP‐9kConclusionsAbstractCalbindin‐D9k(CaBP‐9k) is a cytosolic calcium‐binding protein that is expressed in a variety of tissues, such as uterus, placenta, intestine, kidney, pituitary gland and bone. At present, the precise role(s) of CaBP‐9k remains to be clarified. CaBP‐9k‐null mice are normal, which indicates that other calcium‐transporter genes can compensate for the lack CaBP‐9k. Uterine CaBP‐9k has been shown to be involved in the regulation of myometrial activity by intracellular calcium. In the uterus and placenta,CaBP‐9kexpression is regulated by the sex steroid hormones oestrogen (E2) and progesterone (P4). IntestinalCaBP‐9kis involved in intestinal calcium absorption, and is regulated at the transcriptional and post‐transcriptional levels by 1,25‐dihydroxyvitamin D3, the hormonal form of vitamin D. Thus, evidence to date suggests thatCaBP‐9kmay be regulated in a tissue‐specific manner. In this review, we will summarize current data on the molecular mechanism of regulation ofCaBP‐9kin mammals, including recent research data generated in our laboratories.
Mouse models with human immunity and their application in biomedical research
Authors: Zhang Baojun , Duan Ziyuan , Zhao Yong 
Published: April 2008

Introduction
Recipient mouse selection for engrafting xenogeneic human haematopoietic and immune cells
Pre‐conditioning regimens for establishing humanized mice
Transplantation strategies to establish humanized mice
A proposed ideal humanized mouse model
Applications of humanized mouse models in biomedical research
Conclusions and perspectives

AbstractBiomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)null mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Ragnull mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non‐genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.
Histopathological changes in collagen and matrix metalloproteinase levels in articular condyle of experimental model rats with jaw deformity
Authors: Watanabe A , Yamaguchi M , Utsunomiya T , Yamamoto H , Kasai K 
Published: April 2008

Structured AbstractAuthors –  Watanabe A, Yamaguchi M, Utsunomiya T, Yamamoto H, Kasai KObjective –  To investigate the dynamics of the cartilage matrix in the articular condyle after removal of a side shift plate; Emergence of type I, II, and III collagen in the matrix as well as changes in levels of matrix metalloproteinase (MMP)‐1, ‐8, and ‐13 that degrade collagen were studied histopathologically and immunohistochemically.Design –  Lateral displacement of the mandible was achieved by attaching a side shift plate to the anterior teeth of the maxilla in male rats at 6 weeks. The wearing period of the side shift plate was 8 weeks. Observations were made at 0, 1, 2, 4 and 8 weeks after removal.Results –  In histopathological findings, the timing of proliferation of the layer of hypertrophy varied between the bilateral sides. In immunohistochemical findings a significant decline in the expression of type II collagen in the displacement side was observed immediately after removal. Moreover, the expressions of MMPs were elevated in both sides on 0 weeks. At 1 week after removal, a significant elevated in the expression of type II collagen, MMPs was decline in both sides.Conclusions –  After removal, the levels of MMP‐1, ‐8, and 13 were reduced and the emergence of type II collagen increased. Thus, cellular outgrowth was initiated to trigger intracartilaginous ossification to restore the cartilage matrix.
Exchange transfusion in infants with extreme hyperbilirubinemia: an experience from a developing country
Authors: Salas Ariel A , Mazzi Eduardo 
Published: April 2008

AbstractObjective: To determine the clinical and epidemiological features of infants with extreme hyperbilirubinemia who require exchange transfusion (ET).Study design: Term and near‐term infants admitted to a paediatric hospital over a 5‐year period in La Paz, Bolivia, were included in the study if they met the following criteria: age less than 30 days; total serum bilirubin (TSB) levels ≥428 μmol/L (≥25 mg/dL) on admission and if they had undergone an ET.Results: Fifty‐six infants were identified during the study period. Most of them were exclusively breastfed (98.2%). Median age at admission was 7 days. Weight loss of more than 12% since birth, as well as dehydration, was registered in more than one‐third of cases. Extreme hyperbilirubinemia was considered as secondary to increased enterohepatic circulation (EHC) in most cases (73%). The mean TSB level on admission was 531.8 μmol/L (31.1 mg/dL). Fifteen infants (26.8%) showed signs of acute bilirubin encephalopathy (ABE). Early ABE was reversible after ET in most cases but all infants with advanced ABE developed severe kernicteric sequelae. Nine patients (16.1%) developed adverse events attributable to ET.Conclusions: Dehydration and weight loss in breastfed infants appeared to be an important factor associated with extreme hyperbilirubinemia and secondary brain damage during the first week of life. This may well be avoided if signs of ABE and its associated conditions are identified appropriately by follow‐up programmes.
A new technique for transumbilical insertion of central venous silicone catheters in newborn infants
Authors: Haumont D , De Beauregard V Gouder , Van Herreweghe I , Delanghe G , Ciardelli R , Haelterman E 
Published: April 2008

AbstractAim: A new technique allowing placement of umbilical silicone venous catheters (USVC) is described and compared with percutaneous silicone venous catheters (PSVC).Methods: Data were retrospectively recorded for 198 infants with USVC and 141 infants with PSVC.Results: Overall rate of complications was low and comparable in both groups: thrombosis 1.2%, catheter‐related sepsis 3.5% and mechanical obstruction 5%.Conclusion: A new device allows safe introduction of silicone catheters into the umbilical vein.