bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined hematopoietic and lentiviral gene‐transfer therapies in newborn Twitcher mice reveal contemporaneous neurodegeneration and demyelination in Krabbe disease
Authors: Galbiati F. , Givogri M.I. , Cantuti L. , Lopez Rosas A. , Cao H. , van Breemen R. , Bongarzone E.R. 
Published: January 2009

AbstractThis study characterized the therapeutic benefits of combining hematogenous cell replacement with lentiviral‐mediated gene transfer of galactosylceramidase (GALC) in Twitcher mice, a bona fide model for Krabbe disease. Bone marrow cells and GALC‐lentiviral vectors were administered intravenously without any preconditioning to newborn Twitcher pups before postnatal day 2. Treated Twitchers survived up to 4 months of age. GALC activity remained less than 5% of normal values in the nervous system for the first 2 months after treatment and reached ∼30% in long‐term‐surviving mice. Long‐term reconstitution of GALC activity in the nervous system was provided primarily by infiltrating macrophages and to a lesser extent by direct lentiviral transduction of neural cells. Treated Twitchers had significant preservation of myelin, with a G‐ratio (ratio of the axon diameter to the diameter of the myelinated fiber) in sciatic nerve myelin of 0.75 ± 0.08 compared with 0.85 ± 0.10 in untreated mutants. Although treated mutants had improved locomotor activities during their long‐term survival, they died with symptoms of progressive neurological degeneration, indistinguishable from those seen in untreated Twitchers. Examination of long‐lived Twitchers showed that treated mutants were not protected from developing degeneration of axons throughout the neuroaxis. These results suggest that GALC deficiency not only affects myelinating glia but also leads to neuronal dysfunction. The contemporaneous neuropathology might help to explain the limited efficacy of current gene and cell therapies. © 2009 Wiley‐Liss, Inc.
Identification of neural cell adhesion molecule L1‐derived neuritogenic ligands of the fibroblast growth factor receptor
Authors: Kulahin Nikolaj , Li Shizhong , Kiselyov Vladislav , Bock Elisabeth , Berezin Vladimir 
Published: January 2009

AbstractThe neural cell adhesion molecule L1 plays an important role in axon growth, neuronal survival, and synaptic plasticity. We recently demonstrated that the L1 fibronectin type III (FN3) modules interact directly with the fibroblast growth factor (FGF) receptor (FGFR). Sequence alignment of individual L1 FN3 modules with various FGFs suggested that four sequence motifs located in the third and fifth L1 FN3 modules might be involved in interactions with FGFR. The present study found that corresponding synthetic peptides, termed elcamins 1, 2, 3, and 4, bind and activate FGFR in the absence of FGF1. Conversely, in the presence of FGF1, elcamins inhibited receptor phosphorylation, indicating that the peptides are FGFR partial agonists. Elcamins 1, 3, and 4 dose dependently induced neurite outgrowth in cultured primary cerebellar neurons. The neuritogenic effect of elcamins was dependent on FGFR activation, insofar as the effect was abolished by the receptor inhibition. Thus, the identified peptides act as L1 mimetics with regard to activation of FGFR and induction of neurite outgrowth. © 2009 Wiley‐Liss, Inc.
Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes
Authors: Feldmann Anke , Winterstein Christine , White Robin , Trotter Jacqueline , Krämer‐Albers Eva‐Maria 
Published: January 2009

AbstractOligodendrocytes form the central nervous system myelin sheath by spiral wrapping of their plasma membrane around axons, necessitating a high rate of exocytic membrane addition to the growing myelin membrane. Membrane fusion is mediated by soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor proteins (SNAREs), which act by specific pairing of vesicle (R)‐ and target (Q)‐SNAREs. To characterize oligodendroglial SNAREs and their trafficking pathways, we performed a detailed expression analysis of SNAREs in differentiating cultured oligodendrocytes and myelin and determined their subcellular localization. Expression of the plasma membrane Q‐SNAREs syntaxin 3, syntaxin 4, SNAP23, and the endosomal R‐SNARE VAMP3/cellubrevin increased with oligodendroglial maturation, while the expression of SNAP29 decreased. Interestingly, syntaxin 3, syntaxin 4, and VAMP7/tetanustoxin‐insensitive VAMP accumulated in myelin during development, suggesting a role in myelin membrane fusion. Coimmunoprecipitation from oligodendroglial cell lysates elucidated interactions between SNAREs: for example, Golgi‐localized VAMP4 associated with syntaxin 6 and SNAP29. Furthermore, we identified a cognate core complex composed of VAMP3, syntaxin 4, and SNAP23, which may mediate fusion of endosome‐derived vesicles with the plasma membrane. This study provides a comprehensive analysis of SNARE proteins in oligodendrocytes and assigns defined SNAREs to putative vesicle trafficking pathways in myelinating oligodendrocytes, thus facilitating future functional analysis of distinct SNAREs in oligodendroglial membrane traffic and myelination. © 2009 Wiley‐Liss, Inc.
Targeted mechanical properties for optimal fluid motion inside artificial bone substitutes
Authors: Blecha L.D. , Rakotomanana L. , Razafimahery F. , Terrier A. , Pioletti D.P. 
Published: January 2009

AbstractOur goal was to develop a method to identify the optimal elastic modulus, Poisson's ratio, porosity, and permeability values for a mechanically stressed bone substitute. We hypothesized that a porous bone substitute that favors the transport of nutriments, wastes, biochemical signals, and cells, while keeping the fluid‐induced shear stress within a range that stimulates osteoblasts, would likely promote osteointegration. Two optimization criteria were used: (i) the fluid volume exchange between the artificial bone substitute and its environment must be maximal and (ii) the fluid‐induced shear stress must be between 0.03 and 3 Pa. Biot's poroelastic theory was used to compute the fluid motion due to mechanical stresses. The impact of the elastic modulus, Poisson's ratio, porosity, and permeability on the fluid motion were determined in general and for three different bone substitute sizes used in high tibial osteotomy. We found that fluid motion was optimized in two independent steps. First, fluid transport was maximized by minimizing the elastic modulus, Poisson's ratio, and porosity. Second, the fluid‐induced shear stress could be adjusted by tuning the bone substitute permeability so that it stayed within the favorable range of 0.03 to 3 Pa. Such method provides clear guidelines to bone substitute developers and to orthopedic surgeons for using bone substitute materials according to their mechanical environment. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1082–1087, 2009
Routing runoff and soil particles in a distributed model with GIS: implications for soil protection in mountain agricultural landscapes
Authors: López‐Vicente M. , Navas A. 
Published: January 2009

AbstractSoil erosion by water is a serious threat to crop sustainability and one of the main causes of landscape degradation in Mediterranean environments. The accurate assessment of soil erosion is a first requirement to face the problem of soil loss in highly fragile mountain environments. In this work, single flow (D8), multiple flow (MD) and combined flow (MDD) algorithms are used to compute cumulative runoff. Effective runoff is estimated after accounting infiltration and soil surface properties and added to the revised Morgan, Morgan and Finney (RMMF) model of soil erosion at the ‘Laguna Grande de Estaña’ catchment (Spanish pre‐Pyrenees). The combined flow algorithm explicitly associated to the gullies (MDD8‐G) leads to a more realistic assessment of runoff pathways. The MD algorithm generates unrealistic maps of concentrated runoff in gullies and overestimates soil erosion rates (average rate of 75 Mg ha−1 y−1). The D8 and MDD8‐G algorithms estimate similar values of soil erosion (average rates of 37 and 44 Mg ha−1 y−1, respectively). Paths, crops on steep slopes, open Mediterranean forest and sparse scrublands have the highest values of soil erosion (more than 50 Mg ha−1 y−1). The estimated rates with the MDD8‐G algorithm in control points in crops, forest and scrublands fit better with available data from 137Cs than those obtained with the D8 algorithm. Therefore, the MDD8‐G algorithm improves the quality predictions of soil erosion and is of interest to study processes of overland flow in Mediterranean environments with presence of gullies. Copyright © 2009 John Wiley & Sons, Ltd.
Studying the effects of Mahonia aquifolium populations on small‐scale mountain agro‐ecosystems in Hungary with the view to minimise land degradation
Authors: Hudek C. , Rey F. 
Published: January 2009

AbstractAfter the political changeover in Hungary in 1989, many farm owners faced problems typical of a small sized farm (<1 ha) as well as a lack of various resources. This led to many farms with great horticultural backgrounds being abandoned, especially in mountainous areas where erosion control is essential for soil conservation. Severe changes can occur on soil through property abandonment. The local socio‐economic aspects must be taken into consideration as well as the problem of soil degradation as this will be a motivating factor in preservation initiatives. Under horticultural management, Mahonia aquifolium was tested to determine its efficiency in water erosion control in mountainous conditions in Hungary. Soil loss and water runoff were measured after every rainfall event at six different plots: four cultivated M. aquifolium populations with different ages (4, 12, 20 and 25 years old) and two control plots. A bare soil field and a grass field represented the control plots. The results show that as the age of the M. aquifolium populations increase, the cumulative runoff and sediment values decrease. It also showed that 2 years after setting up a new M. aquifolium plantation, the cumulative runoff decreased by 69 per cent and the cumulative soil loss decreased by 74 per cent. This indicates that a M. aquifolium population could play a significant role in erosion control within a short period of time. Copyright © 2009 John Wiley & Sons, Ltd.
Vitamin D receptor modulates the neoplastic phenotype through antagonistic growth regulatory signals
Authors: Xu Haibo , McCann Mella , Zhang Zhiyu , Posner Gary H. , Bingham Victoria , El‐Tanani Mohamed , Campbell Frederick C. 
Published: January 2009

AbstractVitamin D receptor (VDR) can modulate functionally antagonistic growth regulatory pathways, involving β‐catenin/E‐cadherin on one hand and osteopontin (OPN) on the other. This study investigates effects of VDR ligand treatment on the balance of these discordant signals and on associated cell behavior. Treatment of Rama 37 or SW480 cells by 1α,25‐(OH)2 D3 or analogs suppressed β‐catenin/Lef‐1/Tcf signaling and upregulated E‐cadherin, consistent with a cancer‐inhibitory action. Conversely, treatment also increased transcription of OPN that may be implicated in tumor progression. Molecular crosstalk was observed between the antagonistic VDR‐dependent signals, in that β‐catenin/Lef‐1/Tcf molecules modulated VDR activation of OPN. Treatment effects on cell growth were related to a constitutive balance of OPN and E‐cadherin expression. No growth effects were observed in Rama 37 cells that have low OPN and high E‐cadherin expression. Conversely, treatment of Rama 37 stably transfected subclones that had high OPN and/or low level E‐cadherin induced small but significant increases of cell attachment to fibronectin, anchorage‐independent growth or invasion. This study shows that relative expression levels of key VDR downstream genes may influence growth regulation by 1α,25‐(OH)2 D3 or analogs. These findings may be relevant to the cell‐ or tissue‐specificity of vitamin D growth regulation. © 2009 Wiley‐Liss, Inc.
Hepatocyte growth factor induces hypoxia‐related interleukin‐8 expression in lung adenocarcinoma cells
Authors: Chiang Yung‐Yen 
Published: January 2009

AbstractRapid growth of cancer cells often creates insufficient supply of oxygen and nutrients in the tumour nest. The frequent detection of hypoxia‐inducible factor (HIF) and interleukin‐8 (IL‐8) in afflicted tissues suggests that IL‐8 expression could be associated with elevated levels of HIF. Recently, we found that hypoxia also upregulated the expression of hepatocyte growth factor (HGF) in lung adenocarcinoma (LAD) cells. However, the relationship between HGF and IL‐8 has not been investigated in LAD cells. In this study, we found that HGF induced IL‐8 expression in LAD. Interestingly, hypoxia also increased the level of prostaglandin F2α (PGF2α), a product of dihydrodiol dehydrogenase (DDH). When expression of DDH was suppressed by siRNA, the levels of PGF2α, HGF and IL‐8 were reduced; however, their levels returned to normal after DDH was reintroduced. These data suggest that hypoxia induces biosynthesis of PGF2α, which then activates HGF and IL‐8 expression. The results provide a reasonable explanation of how PGF2α, HGF and IL‐8 exert their effects on cancer cell metastasis. © 2009 Wiley‐Liss, Inc.
Reproducibility assessment of a multiple reference tissue method for quantitative dynamic contrast enhanced–MRI analysis
Authors: Yang Cheng , Karczmar Gregory S. , Medved Milica , Oto Aytekin , Zamora Marta , Stadler Walter M. 
Published: January 2009

AbstractBone metastases of 16 prostate cancer patients were scanned twice 1 week apart by dynamic contrast enhanced (DCE) –MRI at 2‐s resolution using a two‐dimensional gradient‐echo pulse sequence. With a multiple reference tissue method (MRTM), the local tissue arterial input function (AIF) was estimated using the contrast agent enhancement data from tumor subregions and muscle. The 32 individual AIFs estimated by the MRTM, which had considerable intra‐patient and inter‐patient variability, were similar to directly measured AIFs in the literature and using the MRTM AIFs in a pharmacokinetic model to derive estimated individual cardiac outputs provided physiologically reasonable results. The MRTM individual AIFs gave better fits with smaller sum of squared errors and equally reproducible estimate of kinetic parameters compared with a previous reported population AIF measured from remote arteries. The individual MRTM AIFs were also used to obtain a mean local tissue AIF for the unique population of this study, which further improved the reproducibility of the estimated kinetic parameters. The MRTM can be applied to DCE‐MRI studies of bone metastases from prostate cancers to provide an AIF from which reproducible quantitative DCE‐MRI parameters can be derived, thus help standardize DCE‐MRI studies in cancer patients. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Borneo records of Malay tapir, Tapirus indicus Desmarest: a zooarchaeological and historical review
Authors: Cranbrook Earl of , Piper P. J. 
Published: January 2009

AbstractThe Malay tapir, Tapirus indicus Desmarest 1819, currently has a patchy distribution that covers parts of Myanmar, southern Thailand, Peninsular Malaysia and the island of Sumatra. The palaeontological record extends its past range to include China and the Greater Sunda islands of Java and Borneo. A compilation of specimens from cave excavations in the Malaysian states of Sarawak and Sabah, including finds reported here for the first time, shows that Malay tapirs occurred in northern Borneo from the late Upper Pleistocene, ca. 45,000 years ago, through Holocene to near recent dates. The palaeo‐population of Borneo tended to be slightly smaller than extant Tapirus indicus of Peninsular Malaysia and Sumatra, but taxonomically inseparable. While undoubtedly present in the archaeological record through the activities of human cave visitors, it is likely that tapirs were not the targeted quarry of hunting practices directed mainly at bearded pigs. Their representation among overall finds of medium and large mammal remains in the Sunda region shows that tapirs were rare in all environments from Middle Pleistocene to Holocene. Their present ecology indicates that climate change of the post‐Pleistocene, with restoration of the humid tropical rainforest environment, would have reduced the extent of available habitat favourable to the species. Although no authenticated museum specimens have been obtained in Borneo, these archaeological results give plausibility to anecdotal reports of the 19th and early 20th centuries. It is possible that the final disappearance of the tapir from the island was a recent phenomenon. Copyright © 2009 John Wiley & Sons, Ltd.
Acute hypoxia and osteoclast activity: a balance between enhanced resorption and increased apoptosis
Authors: Knowles Helen J , Athanasou Nicholas A 
Published: January 2009

AbstractOsteoclasts are the primary mediators of pathological bone resorption in many conditions in which micro‐environmental hypoxia is associated with disease progression. However, effects of hypoxia on human osteoclast activity have not been reported. Mature human osteoclasts were differentiated from peripheral blood or obtained from giant cell tumour of bone. Osteoclasts were exposed to a constant hypoxic environment and then assessed for parameters including resorption (toluidine blue staining of dentine slices), membrane integrity (trypan blue exclusion), apoptosis (TUNEL, DAPI), and osteolysis‐associated enzyme activity (TRAP, cathepsin K). 24 h exposure to 2% O2 produced a 2.5‐fold increase in resorption associated with increased TRAP and cathepsin K enzyme activity. Hypoxia‐Inducible Factor‐1α (HIF‐1α) siRNA completely ablated the hypoxic increase in osteoclast resorption. 24 h at 2% O2 also increased the number of osteoclasts with compromised membrane integrity from 6% to 21%, with no change in the total osteoclast number or the proportion of late‐stage apoptotic cells. Transient reoxygenation returned the percentage of trypan blue‐positive cells to normoxic levels, suggesting that osteoclasts can recover from the early stages of cell death. Repeated over an extended period, hypoxia/reoxygenation enhanced osteoclast differentiation at this pO2. These data suggest that in diseased bone, where the pO2 may fall to ≤2% O2, a delicate balance between hypoxia‐induced osteoclast activation and hypoxia‐induced osteoclast apoptosis mediates pathological bone resorption. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The significance of fetal ventriculomegaly: etiology, short‐ and long‐term outcomes
Authors: Gaglioti Pietro , Oberto Manuela , Todros Tullia 
Published: January 2009

AbstractFetal cerebral ventriculomegaly (VM) is diagnosed when the width of one or both ventricles, measured at the level of the glomus of the choroid plexus (atrium), is ≥ 10 mm. VM can result from different processes: abnormal turnover of the cerebrospinal fluid (CSF), neuronal migration disorders, and destructive processes. In a high percentage of cases, it is associated with structural malformations of the central nervous system (CNS), but also of other organs and systems. The rate of associated malformations is higher (≥60%) in severe VM (>15 mm) and lower (10–50%) in cases of borderline VM (10–15 mm). When malformations are not present, aneuploidies are found in 3–15% of borderline VM; the percentage is lower in severe VM. The neurodevelopmental outcome of isolated VM is normal in > 90% of cases if the measurement of ventricular width is between 10 and 12 mm; it is less favorable when the measurement is > 12 mm. Copyright © 2009 John Wiley & Sons, Ltd.
Disorders of prosencephalic development
Authors: Volpe P. , Campobasso G. , De Robertis V. , Rembouskos G. 
Published: January 2009

AbstractAbnormal ventral induction may result in disorders of formation, cleavage, and midline development of prosencephalic structures. Holoprosencephaly is a developmental field defect of impaired cleavage of prosencephalon. The most widely accepted classification of holoprosencephaly recognizes three major varieties: the alobar, semilobar and lobar types, according to the severity of the malformation. The brain malformations, characterized by the fusion of the cerebral hemisphere along the midline are commonly associated with facial anomalies.Corpus callosum agenesis and septo‐optic dysplasia are disorders of prosencephalic midline development, and usually have less severe presentations but still, affected subjects may suffer from neurodevelopmental retardation, and/or endocrinologic and visual disorders.In this article we report an up‐to‐date of pathogenesis, prenatal sonographic findings, differential diagnosis and prognosis of the aforementioned anomalies. Copyright © 2009 John Wiley & Sons, Ltd.
Structure and property of injection‐molded polypropylene along the flow direction
Authors: Yu Xiaofeng , Wu Hong , Li Jiang , Guo Shaoyun , Qiu Jianhui 
Published: January 2009

AbstractThe structure and mechanical properties of injection‐molded polypropylene along the flow direction were investigated in this article. A remarkable difference was found in morphology and mechanical properties of the injection‐molded parts along the flow direction. The three‐layered structure (namely the skin, subskin, and core layer) showed a gradient distribution along the flow direction. The IR and WAXD results showed that the orientation of the subskin layer in the gate part is much higher than that in the far part. DSC analysis results indicated that the two parts (gate part and far part) of injection‐molded bar has the same degree of crystallinity that should not be responsible for the mechanical difference of the two parts. According to the measurement of residual internal stress, there is large difference between the gate part and far part, which is the main reason leading to the difference of impact behavior. The annealing treatment eliminated the internal stress, so the mechanical difference between the two parts decreased and the fracture type of the far part changed from brittle to ductile. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers
Organoclay‐filled caprolactam‐blocked methylenediphenyl diisocyanate‐toughened epoxy interpenetrating network matrices
Authors: Premkumar S. , Karikal Chozhan C. , Alagar M. 
Published: January 2009

AbstractAn interpenetrating networks of varying weight percentages (5, 10, and 15%) of caprolactam‐blocked methylenediphenyl diisocyanate(CMDI)‐toughened epoxy matrices were developed and characterized. The toughened epoxy system was further modified with 1, 3, and 5% (by wt) of organophilic montmorillonite (MMT) clay. Organoclay‐filled hybrid CMDI‐epoxy matrices, developed in the form of castings, were characterized for their thermomechanical properties. The data obtained from differential scanning calorimetry and dynamic mechanical analysis showed that there was a significant loss in the values of glass transition temperatures (Tg) of organoclay‐filled hybrid epoxy systems when compared with that of neat epoxy resin, whereas increasing trend in thermal stability was observed. The values obtained from mechanical studies indicated that the CMDI‐toughened epoxy and organoclay‐filled CMDI‐epoxy systems were improved the mechanical properties according to its percentage concentration. From X‐ray diffraction analysis, it was observed that the presence of d001 reflections of the organophilic MMT clay in the CMDI‐toughened epoxy systems indicated the development of intercalated clay structure which in turn confirmed the formation of intercalated nanocomposites. Homogeneous surface morphologies of CMDI‐toughened epoxy and organoclay‐filled CMDI‐toughened epoxy systems were ascertained from scanning electron microscope. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers