bluuebunny/crossref_metadata_2025 huggingface dataset:
H‐ferritin is the major source of iron for oligodendrocytes
Authors: Todorich Bozho , Zhang Xuesheng , Connor James R.
Published: March 2011

There is a critical relationship between oligodendrocyte development, myelin production, and iron bioavailability. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding molecular mechanisms of iron import into oligodendrocytes is necessary for devising effective strategies for iron supplementation. Although transferrin has been considered as an essential component of oligodendrocyte media in culture, oligodendrocytes in vivo lack transferrin receptors. We have established that receptors for H‐ferritin (HF) exist on cells of oligodendroglial lineage and that uptake of extracellular HF by oligodendrocyte progenitors is via receptor mediated endocytosis. These data strongly argue that ferritin is a major source of iron for oligodendrocytes. In this study, we demonstrate that media deficient in transferrin results in loss of viability of oligodendrocyte progenitors in culture. Cell loss could be prevented by supplementing the media with HF. Moreover, the addition of extracellular HF stimulates development of oligodendrocyte progenitor cells (OPCs) by increasing expression of myelin basic protein (MBP) and olig2 proteins without increasing their proliferation. The effect of HF on the OPCs could be mimicked by addition of membrane permeable 3,5,5‐trimethylhexanoyl ferrocene (TMH‐Fe) as an iron source to the media, but not membrane‐impermeable ferric ammonium citrate. Overall, therefore, our results demonstrate the importance of iron for OPCs viability and differentiation and identify extracellular HF as a critical source of iron for oligodendrocytes. Given that ferritin receptors, but not transferrin receptors can be demonstrated on oligodendrocytes in vivo, the delivery of iron to oligodendrocytes viaferritin may be the more biological relevant delivery system. © 2011 Wiley‐Liss, Inc.
Regenerating islet‐derived family member, 4 modulates multiple receptor tyrosine kinases and mediators of drug resistance in cancer
Authors: Vanderlaag Kathryn , Wang Wei , Fayadat‐Dilman Laurence , Wagner Janet , Bald Laura , Grein Jeff , Janatpour Mary J.
Published: March 2011

Regenerating islet‐derived family member, 4 (Reg IV) is a secreted protein and member of the C‐type lectin superfamily. Expression analyses have characterized Reg IV as a prognostic marker for certain cancers; however, the functional role of Reg IV in cancer, including downstream signaling, has only begun to be elucidated. To investigate the biological role of Reg IV in cancer, phosphorylation events were studied in cancer cell lines in the context of either Reg IV stimulation (HCT116 cells) or knockdown of endogenous Reg IV (PC3 and KM12 cells). In addition to the previously observed impact on epidermal growth factor receptor and Akt phosphorylation, we observed modulation in the phosphorylation of multiple additional receptor tyrosine kinases (RTKs), including insulin receptor, insulin‐like growth factor receptor as well as their downstream effectors, mitogen‐activated protein kinase and phosphatidylinositol‐3‐kinase pathways. Furthermore, knockdown of Reg IV impacted the ability of insulin and EGF to stimulate downstream tyrosine phosphorylation. Knockdown of Reg IV in cancer cell lines inhibited anchorage‐dependent and anchorage‐independent (both soft‐agar and spheroid assays) cell growth and induced cell cycle arrest. This was accompanied by upregulation of p21 and p27. Transiently silencing Reg IV in cancer cells induced apoptosis and downregulated Bcl‐2. Conversely, stimulation of HCT116 cells with recombinant Reg IV induced Bcl‐2. Hsp27, a molecule implicated in drug resistance, was similarly modulated by Reg IV. Consistent with our observations with Reg IV siRNA‐mediated knockdown, monoclonal antibodies directed against Reg IV inhibited PC3 and KM12 cell growth. Collectively, Reg IV plays an important role in cancer by modulation of key signaling molecules including Hsp27, Bcl‐2 and multiple RTKs.
Human melanoma cells express FGFR/Src/Rho signaling that entails an adhesion‐independent caveolin‐1 membrane association
Authors: Fecchi Katia , Travaglione Sara , Spadaro Francesca , Quattrini Adriano , Parolini Isabella , Piccaro Giovanni , Raggi Carla , Fabbri Alessia , Felicetti Federica , Carè Alessandra , Fiorentini Carla , Sargiacomo Massimo
Published: March 2011

Caveolae have been indicated as a center of cytoskeleton regulation for Src kinase/Rho GTPase signaling. In addition, Src recruitment on intact cortical actin cytoskeleton appears to be required for bFGF/FGFR signal activation. Recently, we established a relationship between caveolin‐1 (Cav‐1) expression and cell migration in human malignant melanoma, constitutively activated by a bFGF autoregulatory loop. This work intends to investigate whether caveolae's asset, through bFGF/FGFR/c‐Src/Rho signaling, could be related to melanoma cell anchorage. Accordingly, we revealed the existence of a FGFR/Src kinase pathway in Cav‐1 enriched detergent‐resistant membranes (DRMs) of Me665/1 metastatic melanoma cells, as confirmed by FGFR silencing. Moreover, we determined the expression and phosphorylation levels of Cav‐1/Src/Erk signal pathway as a function of FGFR activation and cell density. A sucrose density gradient ultracentrifugation was employed to monitor Cav‐1 membrane association and buoyancy in Me665/1 cells treated for actin fragmentation or for altered phosphorylation signals. As a result, melanoma cells show remarkable resistance to Cav‐1 disassembly, together with persisting cell signal activity, being Src and Cav‐1 crucial modulators of Rho GTPases. In conclusion, our study primarily highlights, in a metastatic melanoma cell line expressing caveolin, the circumstances whereby caveola structural and functional endurance enables the FGFR/Src/Rho GTPases pathway to keep on cell progression.
Long‐term exposure of gastrointestinal stromal tumor cells to sunitinib induces epigenetic silencing of the PTEN gene
Authors: Yang Jing , Ikezoe Takayuki , Nishioka Chie , Takezaki Yuka , Hanazaki Kazuhiro , Taguchi Takahiro , Yokoyama Akihito
Published: March 2011

Although sunitinib possesses significant clinical effects on imatinib‐resistant gastrointestinal stromal tumors (GISTs), the individuals with GIST eventually become resistant to treatment with this tyrosine kinase inhibitor. The mechanism of resistance to sunitinib is still under investigation. To address this issue, we have established sunitinib‐resistant GIST‐T1 sublines (designated as GIST‐T1R) by culturing cells with increasing concentrations of sunitinib. GIST‐T1R cells were also resistant to imatinib‐mediated growth inhibition. Examination of intracellular signaling found that Akt/ mammalian target of rapamycin (mTOR) signaling remained activated in GIST‐T1R but not in parental GIST‐T1 cells, after exposure of these cells to sunitinib, as measured by immunoblotting. Further study found that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was silenced by methylation of the promoter region of the gene. Notably, forced‐expression of PTEN in GIST‐T1R cells negatively regulated the Akt/mTOR pathways and sensitized these cells to sunitinib‐mediated growth arrest and apoptosis. Taken together, epigenetic silence of PTEN might be one of the mechanisms which cause drug‐resistance in individuals with GIST after exposure to tyrosine kinase inhibitors. Blockade of the PI3K/Akt signaling with the specific inhibitors could be useful in such a case.
Inhibition of activated receptor tyrosine kinases by Sunitinib induces growth arrest and sensitizes melanoma cells to Bortezomib by blocking Akt pathway
Authors: Yeramian Andree , Sorolla Anabel , Velasco Ana , Santacana Maria , Dolcet Xavier , Valls Joan , Abal Leandre , Moreno Sara , Egido Ramón , Casanova Josep M. , Puig Susana , Vilella Ramón , Llombart‐Cussac Antonio , Matias‐Guiu Xavier , Martí Rosa M.
Published: March 2011

Despite the use of multiple therapeutic strategies, metastatic melanoma remains a challenge for oncologists. Thus, new approaches using combinational treatment may be used to try to improve the prognosis of this disease. In this report, we have analyzed the expression of receptor tyrosine kinases (RTKs) in melanoma specimens and in four metastatic melanoma cell lines. Both melanoma specimens and cell lines expressed RTKs, suggesting that they may represent eventual targets for multitargeted tyrosine kinase inhibitor, Suntinib. Sunitinib reduced the proliferation of two melanoma cell lines (M16 and M17) and increased apoptosis in one of them (M16). Moreover, the two metastatic melanoma cell lines harbored an activated receptor (PDGFRα and VEGFR, respectively), and Sunitinib suppressed the phosphorylation of the RTKs and their downstream targets Akt and ribosomal protein S6, in these two cell lines. Similar results were obtained when either PDGFRα or VEGFR2 expression was silenced by lentiviral‐mediated short‐hairpin RNA delivery in M16 and M17, respectively. To evaluate the interaction between Sunitinib and Bortezomib, median dose effect analysis using MTT assay was performed, and combination index was calculated. Bortezomib synergistically enhanced the Sunitinib‐induced growth arrest in Sunitinib‐sensitive cells (combination index < 1). Moreover, LY294002, a PI3K inhibitor, sensitized melanoma cells to Bortezomib treatment, suggesting that downregulation of phospho‐Akt by Sunitinib mediates the synergy obtained by Bortezomib + Sunitinib cotreatment. Altogether, our results suggest that melanoma cells harboring an activated RTK may be clinically responsive to pharmacologic RTK inhibition by Sunitinib, and a strategy combining Sunitinib and Bortezomib, may provide therapeutic benefit.
Downregulation of zinc finger protein 132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis
Authors: Abildgaard Mette Opstrup , Borre Michael , Mortensen Martin Mørck , Ulhøi Benedicte P. , Tørring Niels , Wild Peter , Kristensen Helle , Mansilla Francisco , Ottosen Peter D. , Dyrskjøt Lars , Ørntoft Torben F. , Sørensen Karina Dalsgaard
Published: March 2011

This study investigates the expression and biomarker potential of zinc finger protein 132 (ZNF132) in prostate cancer (PC) by transcriptional profiling and immunohistochemical analysis of tissue microarrays, including tumor specimens from 615 radical prostatectomy (RP) patients and 199 conservatively treated patients. Primary clinical endpoints were time to PSA recurrence and cancer‐specific death, respectively. Compared to normal prostate epithelial cells from men without PC, ZNF132 transcript levels were significantly reduced in PC cells from patients with localized PC and further downregulated in metastatic PC. Likewise, ZNF132 protein expression was significantly lower in primary tumors from patients with metastatic compared to localized PC and further reduced in castrate‐refractory PC, indicating that ZNF132 downregulation correlates with disease progression. Reduced ZNF132 immunoreactivity was significantly associated with high Gleason score and advanced T stage in both PC patient cohorts. By univariate analysis, no/weak ZNF132 staining was a significant adverse predictor of PSA recurrence after RP (p = 0.024) and cancer‐specific death following conservative treatment (p = 0.009). In multivariate models, however, ZNF132 did not add significant independent value to established prognostic factors. Finally, bisulfite sequencing revealed frequent promoter hypermethylation of ZNF132 in both PC cell lines and PC tissue samples, indicating that ZNF132 is epigenetically silenced in PC. In summary, our results show that downregulation of ZNF132 is associated with aggressive PC and furthermore identify ZNF132 as a new candidate methylation marker for PC.
Ligand migration in human indoleamine‐2,3 dioxygenase
Authors: Nienhaus Karin , Nickel Elena , Lu Changyuan , Yeh Syun‐Ru , Nienhaus G. Ulrich
Published: March 2011

Human indoleamine 2,3‐dioxygenase (hIDO), a monomeric heme enzyme, catalyzes the oxidative degradation of L‐tryptophan (L‐Trp) and other indoleamine derivatives. Its activity follows typical Michaelis–Menten behavior only for L‐Trp concentrations up to 50 μM; a further increase in the concentration of L‐Trp causes a decrease in the activity. This substrate inhibition of hIDO is a result of the binding of a second L‐Trp molecule in an inhibitory substrate binding site of the enzyme. The molecular details of the reaction and the inhibition are not yet known. In the following, we summarize the present knowledge about this heme enzyme. © 2011 IUBMB IUBMB Life, 63(3): 153–159, 2011
Ligand migration in the truncated hemoglobin of Mycobacterium tuberculosis
Authors: Heroux Maxime S. , Mohan Anne D. , Olsen Kenneth W.
Published: March 2011

The truncated hemoglobin of Mycobacterium tuberculosis (Mt‐trHbO) is a small heme protein belonging to the hemoglobin superfamily. Truncated hemoglobins (trHbs) are believed to have functional roles such as terminal oxidases and oxygen sensors involved in the response to oxidative and nitrosative stress, nitric oxide (NO) detoxification, O2/NO chemistry, O2 delivery under hypoxic conditions, and long‐term ligand storage. Based on sequence similarities, they are classified into three groups. Experimental studies revealed that all trHbs display a 2‐on‐2 α‐helical sandwich fold rather than the 3‐on‐3 α‐helical sandwich fold of the classical hemoglobin fold. Using locally enhanced sampling (LESMD) molecular dynamics, the ligand‐binding escape pathways from the distal heme binding cavity of Mt‐trHbO were determined to better understand how this protein functions. The importance of specific residues, such as the group II and III invariant W(G8) residue, can be seen in terms of ligand diffusion pathways and ligand dynamics. LESMD simulations show that the wild‐type Mt‐trHbO has three diffusion pathways while the W(G8)F Mt‐trHbO mutant has only two. The W(G8) residue plays a critical role in ligand binding and stabilization and helps regulate the rate of ligand escape from the distal heme pocket. Thus, this invariant residue is important in creating ligand diffusion pathways and possibly in the enzymatic functions of this protein. © 2011 IUBMB IUBMB Life, 63(3): 214–220, 2011
Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions
Authors: Ascenzi Paolo , Polticelli Fabio , Marino Maria , Santucci Roberto , Coletta Massimo
Published: March 2011

Cytochrome c (cytc) is pivotal in mitochondrial respiration and apoptosis. The heme‐Fe‐atom of native hexacoordinated horse heart cytc (hhcytc) displays a very low reactivity toward ligands and does not exhibit catalytic properties. However, on interaction with cardiolipin (CL), hhcytc changes its tertiary structure disrupting the heme‐Fe‐Met80 distal bond. The CL‐hhcytc complex displays a very low midpoint potential, out of the range required for its physiological role, binds CO and NO with high affinity, facilitates peroxynitrite isomerization to NO3−, and displays peroxidase activity. As a whole, the CL‐hhcytc complex could play either proapoptotic effects, catalyzing lipid peroxidation and the subsequent hhcytc release into the cytoplasm, orantiapoptotic actions, such as scavenging peroxynitrite (i.e., protecting the mitochondrion from reactive nitrogen and oxygen species), and binding of CO and NO (i.e., inhibiting lipid peroxidation and hhcytc traslocation). Here, the CL‐driven allosteric modulation of hhcytc properties is reviewed, highlighting proapoptotic and antiapoptotic actions. © 2011 IUBMB IUBMB Life, 63(3): 160–165, 2011
Changes in hip fracture rates in southeastern Australia spanning the period 1994–2007
Authors: Pasco Julie A , Brennan Sharon L , Henry Margaret J , Nicholson Geoffrey C , Sanders Kerrie M , Zhang Yu , Kotowicz Mark A
Published: March 2011

Hip fracture incidence rates appear to be declining in Western populations. Utilizing comprehensive incident hip fracture data from radiology reports, we determined changes in hip fracture rates in southeastern Australia between 1994–1996 and 2006–2007 for residents aged 55 years or older. During this period, the population at risk increased by 47% for men and 40% for women. Although the absolute number of hip fractures increased by 53% in men and 4.4% in women, standardized hip fracture ratios were 0.92 [95% confidence interval (CI) 0.79–1.08] and 0.69 (95% CI 0.62–0.77), respectively. Marked reductions in hip fracture rates were observed for women: 32% for ages 75 to 84 years and 29% for ages 85 years or older. Data from the Geelong Osteoporosis Study were used to identify changes in body composition and lifestyle that might have influenced hip fracture risk in women during this period. Between 1993–1997 and 2004–2008, there was an increase in adiposity, bone mineral density (BMD), healthy lifestyles, and exposure to bone-active drugs; use of hormone therapy declined. Thus hip fracture incidence rates have decreased from the mid-1990 s to the mid-2000 s, the effect being greater among women. Our data also suggest that the recent increase in adiposity and consequent increase in BMD at the hip may have contributed to this decline. However, improved efficacy and increased uptake of antifracture drug treatments, other cohort effects, or other environmental influences cannot be excluded. © 2011 American Society for Bone and Mineral Research.
Differential expression of complement proteins in cerebrospinal fluid from active multiple sclerosis patients
Authors: Li Yun , Qin Zhaoyu , Yang Mingchong , Qin Yanjiang , Lin Chengzhao , Liu Shilian
Published: March 2011

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with complex immunopathogenesis. Using the 2‐D DIGE technology, we separate CSF proteins from patients with active MS and control subjects. Three of the seven differential proteins identified were related with complement system, and the network analysis of the differential proteins revealed complement activation involvement in active MS. Complement C4b (gamma chain) was confirmed elevated by performing western blotting analysis (P < 0.01). The present results are an independent quantitative proteomic measure in CSF from active MS patients. The differential expression of the complement C4b and related proteins in CSF provides potential biomarkers as well as evidence for the involvement of complement activation in the pathogenesis of MS disease. J. Cell. Biochem. 112: 1930–1937, 2011. © 2011 Wiley‐Liss, Inc.
Microwave treated activated carbon from industrial waste lignin for endosulfan adsorption
Authors: Maldhure Atul V. , Ekhe Jayant D.
Published: March 2011

BACKGROUND: Disposal of large amounts of recurring industrial waste lignin is a big problem for the paper industries and there is need for a rational alternative to utilize this waste lignin. Thus highly porous activated carbons (ACs) were prepared from lignin using H3PO4 as an activating chemical with and without microwave treatment in a self‐generated environment at 600 °C and the influence of different types of impregnation on the adsorption–desorption capacities of endosulfan from a liquid phase was studied.

RESULT: The maximum adsorption capacities (Xm) for ACs prepared by a microwave treatment and using a simple impregnation method were 6.2422 mg g−1 and 3.9557 mg g−1, respectively. Equilibrium adsorption time determined from kinetic experiments was 5 h and the experimental kinetic data were described by a pseudo‐second‐order rate model. Surface characteristics and desorption patterns showed considerable difference between the two ACs with the microwave treated AC showing less hysteresis, greater Xm and established overall superiority over the other.

CONCLUSION: Use of microwave treatment produced more oxygen surface functional groups. Results indicate that surface chemistry of the microwave treated sample is more important than the textural properties for the higher adsorption of endosulfan. The microwave treated sample also resulted in less hysteresis and fewer carbonyl surface groups. Desorption patterns cannot be predicted from adsorption alone. Copyright © 2011 Society of Chemical Industry
Clonal selection of high producing, stably transfected HEK293 cell lines utilizing modified, high‐throughput FACS screening
Authors: Song Michael , Raphaelli Kristin , Jones Martina L. , Aliabadi‐Zadeh Khosrow , Leung Kar Man , Crowley David , Hughes Benjamin , Mahler Stephen , Gray Peter P. , Huang Edwin P. , Chin David Y.
Published: March 2011

BACKGROUND: Human embryonic kidney‐293 (HEK‐293) cells are commonly used as a transient expression host but their application in stable therapeutic protein production is limited. This is presumably due to the absence of a suitable amplifiable expression system and hence limited protein output compared with other mammalian cells such as Chinese hamster ovary cells. This paper describes a rapid clonal selection method for isolating HEK293 cell lines with high specific productivity, for a non‐amplifiable expression system, to achieve high‐level, scalable expression of recombinant antibodies.

RESULTS: Flow cytometry utilizing cold capture of secreted protein on the cell surface was applied to isolate high expressing clones from a stable antibiotic resistant pool. The top three isolated clones showed a five‐ to seven‐fold improvement in volumetric outputs compared with the initial resistant pool (∼20 mg L−1) under batch conditions. In fed‐batch conditions using commercially available hydrolysate supplements, the final titre was further increased to 500–600 mg L−1 in shaker flasks. One clone was scaled up to 25 L bag production using a similar hydrolysate feeding regime. The antibody titre reached 655 mg L−1, and 12 g of antibody was recovered after purification, demonstrating scalability of the process. The process of clonal selection through to fed‐batch production of gram quantities was completed within 4 months.

CONCLUSION: HEK‐293 cells can be used as a stable host for the production of biopharmaceuticals, producing gram quantities of recombinant proteins for preclinical development. Copyright © 2011 Society of Chemical Industry
A scalable Nenitzescu synthesis of 2‐methyl‐4‐(trifluoromethyl)‐1H‐indole‐5‐carbonitrile
Authors: Boros Eric E. , Kaldor Istvan , Turnbull Philip S.
Published: March 2011

2‐Methyl‐4‐(trifluoromethyl)‐1H‐indole‐5‐carbonitrile is a key intermediate in the synthesis of selective androgen receptor modulators discovered in these laboratories. A practical and convergent synthesis of the title compound starting from 4‐nitro‐3‐(trifluoromethyl)phenol and tert‐butyl acetoacetate was developed, including a telescoped procedure for synthesis (without isolation) and Nenitzescu reaction of 2‐trifluoromethyl‐1,4‐benzoquinone. Conversion of the known Nenitzescu indole product to a novel triflate intermediate followed by palladium‐catalyzed cyanation afforded a penultimate carbonitrile. Removal of the C‐3 tert‐butyl ester group on the indole through a decarboxylative pathway completed the synthesis of the title compound in six steps (27% overall yield) from 4‐nitro‐3‐(trifluoromethyl)phenol (five steps, 37% overall yield from tert‐butyl acetoacetate). J. Heterocyclic Chem., (2011).
Synthesis of novel 2‐alkoxy(aralkoxy)‐4H‐[1,2,4]triazolo[1,5‐a]quinazolin‐5‐ones starting with dialkyl‐N‐cyanoimidocarbonates
Authors: Al‐Salahi Rashad , Geffken Detlef
Published: March 2011

A novel series of 2‐alkoxy(aralkoxy)‐4H‐[1,2,4]triazolo[1,5‐a]quinazolines were synthesized employing N‐cyanoimidocarbonates and 2‐hydrazinobenzoic acid as building blocks. Chemical transformation of the inherent lactam moiety in the targeted 2‐alkoxy(aralkoxy)[1,2,4]triazolo[1,5‐a]quinazolines was offered access to a variety of derivatives. J. Heterocyclic Chem., (2011).
Erythrocytes inhibit ligament fibroblast proliferation in a collagen scaffold
Authors: Harrison Sophia L. , Vavken Patrick , Murray Martha M.
Published: March 2011

In this work, we hypothesized that the concentration of erythrocytes in a provisional scaffold would have a significant effect on three of the major biological processes occurring in early wound healing. ACL fibroblast proliferation, collagen production, and scaffold contraction were measured in collagen gels containing fibroblasts and erythrocytes in subphysiologic (1 × 108 erythrocytes/ml), physiologic (1 × 109 erythrocytes/ml), and supraphysiologic (1 × 1010 erythrocytes/ml) concentrations. Fibroblast‐seeded gels containing only platelet‐poor plasma were used as a control group. All gels were cultured for 1, 14, and 21 days. DNA, ELISA for procollagen and scaffold size measurements were used to quantify the three above parameters of wound healing. Samples with concentrations of erythryocytes lower than that in whole blood stimulated greater fibroblast proliferation and scaffold contraction than those with erythrocyte concentrations similar to that in whole blood (p < 0.027; p < 0.03). Increasing the erythrocyte concentration over that in the whole blood stimulated fibroblast collagen production (p < 0.009) and limited scaffold contraction (p < 0.031). Further work examining the role of the erythrocyte in the early provisional scaffold is warranted. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1361–1366, 2011
TNF is required for the induction but not the maintenance of compression‐induced BME signals in murine tail vertebrae: Limitations of anti‐TNF therapy for degenerative disc disease
Authors: Papuga M. Owen , Kwok Edmund , You Zhigang , Rubery Paul T. , Dougherty Paul E. , Pryhuber Gloria , Beck Christopher A. , Hilton Matthew J. , Awad Hani A. , Schwarz Edward M.
Published: March 2011

While bone marrow edema (BME) is diagnostic of spondyloarthropathy, its nature remains poorly understood. In contrast, BME in ankylosing spondylitis is caused by tumor necrosis factor (TNF)‐induced vascular and cellular changes. To investigate the relationship between chronic compression and TNF signaling in compression‐induced BME we utilized a tail vertebrae compression model with WT, TNF‐Tg, and TNFR1&2−/− mice to evaluate: (i) healing following release of chronic compression, (ii) induction of BME in the absence of TNFR, and (iii) efficacy of anti‐TNF therapy. Compression‐induced normalized marrow contrast enhancement (NMCE) in WT was significantly decreased threefold (p < 0.01) within 2 weeks of release, while the NMCE values in TNF‐Tg vertebrae remained elevated, but had a significant decrease (p < 0.05) by 6 weeks after the release of compression. TNFR1&2−/− mice were resistant to compression‐induced BME. Anti‐TNF therapy did not affect NMCE versus placebo. Histological examination revealed that NMCE values significantly correlated with marrow vascularity and cellularity (p < 0.05), which account for 76% of the variability of NMCE. Collectively, these data demonstrate a critical role for TNF in the induction of chronic compression‐induced BME, but not in its maintenance. Amelioration of BME is achieved through biomechanical stability, but is not affected by anti‐TNF therapy. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1367–1374, 2011
Immediate ACL reconstruction prevents microvascular pathophysiology in the Uninjured MCL that is not fully reversed by delayed ACL reconstruction
Authors: Mammoto Takeo , Demcoe Ross , Miller Daniel , Leonard Catherine , Seerattan Ruth , Bray Robert , Salo Paul
Published: March 2011

Anterior cruciate ligament (ACL) injury induces maladaptive vascular responses that degrade medial collateral ligament (MCL) function. The purpose of this study was to determine if early or delayed ACL reconstruction can prevent or reverse the abnormal changes in vascular function that occur in the uninjured MCL after ACL injury. Twenty‐four rabbits were divided into four groups (n = 6); control, ACL‐deficient (ACL‐X), immediate ACL reconstructed (ACL‐IR) and delayed ACL reconstructed (ACL‐DR). After 8 weeks, MCLs were assessed for blood flow, responses to acetylcholine (ACh) and phenylephrine (Phe) and autoregulatory responses, using laser speckle perfusion imaging. In ACL‐X knees, blood flow in the MCL increased by 2.5‐fold compared to control. MCL hyperemia was diminished in ACL‐DR knees and was unaltered in ACL‐IR knees. MCL vasculature was unresponsive to ACh and Phe in ACL‐X. These responses were partially restored by ACL reconstruction. Autoregulatory responses were not significantly different between groups. ACL‐DR decreased hyperemia in the MCL and partially attenuated abnormal MCL vascular responses. ACL‐IR was more effective at preventing MCL hyperemia and preserving vascular responsiveness to ACh and Phe. This suggests that the vascular alterations in the uninjured rabbit MCL are largely caused by abnormal mechanical loading resulting from ACL deficiency and can be prevented through early reconstruction. Early ACL reconstruction could limit the progression of microvascular dysfunction of the MCL, and preserve physiological joint homeostasis. This might prevent joint degeneration and delay the progression of osteoarthritis. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1390–1396, 2011
Effects of lateral ligament sectioning on the stability of the ankle and subtalar joint
Authors: Ringleb Stacie I. , Dhakal Ajaya , Anderson Claude D. , Bawab Sebastain , Paranjape Rajesh
Published: March 2011

Patients with subtalar joint instability are often diagnosed with ankle instability. Only after a prolonged period of time in which a patient does not improve after treatment for ankle instability is subtalar joint instability considered. To develop a clinically relevant method to diagnose subtalar joint instability, the kinematics of the simulated unstable subtalar joint were examined. A 6 degree‐of‐freedom positioning and loading device was developed. Plantarflexion/dorsiflexion, inversion/eversion, and internal/external rotation were applied individually or as coupled motions along with an anterior/posterior drawer. Kinematic data were collected from sensors attached to the calcaneus, talus, and tibia by keeping all the ligaments intact, and by serially sectioning anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), cervical ligament, and talocalceneal interosseous ligament. Kinematic results were reported using Euler angles. The ATFL and CFL contributed talocrural instability, similar to previous studies. The interosseous ligament was the greatest contributor to subtalar joint stability. The hindfoot motion (calcaneus relative to tibia) showed significant increases in motion when the ankle and/or subtalar joint was made to be unstable. Therefore, it is difficult to diagnose subtalar joint instability on physical examination alone. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1459–1464, 2011
Cobalt chromium alloy with immobilized BMP peptide for enhanced bone growth
Authors: Poh Chye Khoon , Shi Zhilong , Tan Xiao Wei , Liang Zhen Chang , Foo Xue Mei , Tan Hark Chuan , Neoh Koon Gee , Wang Wilson
Published: March 2011

Cobalt chromium (CoCr) alloys are widely used in orthopedic practice, however, lack of integration into the bone for long‐term survival often occurs, leading to implant failure. Revision surgery to address such a failure involves increased risks, complications, and costs. Advances to enhancement of bone‐implant interactions would improve implant longevity and long‐term results. Therefore, we investigated the effects of BMP peptide covalently grafted to CoCr alloy on osteogenesis. The BMP peptide was derived from the knuckle epitope of bone morphogenic protein‐2 (BMP‐2) and was conjugated via a cysteine amino acid at the N‐terminus. X‐ray photoelectron spectroscopy and o‐phthaldialdehyde were used to verify successful grafting at various stages of surface functionalization. Surface topography was evaluated from the surface profile determined by atomic force microscopy. Osteoblastic cells (MC3T3‐E1) were seeded on the substrates, and the effects of BMP peptide on osteogenic differentiation were evaluated by measuring alkaline phosphatase (ALP) activity and calcium mineral deposition. The functionalized surfaces showed a twofold increase in ALP activity after 2 weeks incubation and a fourfold increase in calcium content after 3 weeks incubation compared to the pristine substrate. These findings are potentially useful in the development of improved CoCr implants for use in orthopedic applications. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1424–1430, 2011
Regulation of the inflammatory response by tin protoporphyrin IX in the rat anterior cruciate ligament transection model of osteoarthritis
Authors: Braza‐Boïls Aitana , Alcaraz Maria José , Ferrándiz Maria Luisa
Published: March 2011

The purpose of this study was to investigate several inflammatory mediators and cartilage degradation molecules as possible biomarkers of joint lesion in the anterior cruciate ligament transection (ACLT) model of osteoarthritis in rats. We also assessed whether the treatment with the anti‐inflammatory agent tin protoporphyrin IX (SnPP) reduces the progression of disease. Our results indicate that serum levels of interleukin (IL)‐6 and PGE2 are significantly increased in ACLT rats 10 weeks after surgery, whereas the increases in IL‐1β and tumor necrosis‐α were not significant. In addition, our data suggest that IL‐17 is the main pro‐inflammatory cytokine in the ACLT joint. We have shown that serum C‐telopeptide of type II collagen (CTX‐II) is a biomarker better than cartilage oligomeric matrix protein, whereas hyaluronic acid showed no correlation with disease progression. Administration of SnPP (i.p. 12 mg/kg BW/day for 10 weeks) reduces the severity of structural changes and the levels of CTX‐II, IL‐6, and PGE2 in serum and IL‐17 and PGE2 in ACLT knees. These effects on PGE2 are dependent on the down‐regulation of cyclooxygenase‐2. Our findings indicate that systemic and local inflammatory mediators participate in the rat ACLT model and anti‐inflammatory strategies may help to reduce the progression of joint lesion. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1375–1382, 2011
Micro‐Raman spectroscopic investigations of mineral assemblages in parallel to bedding laminae in 2.9 Ga sandstones of the Pongola Supergroup, South Africa
Authors: Bower Dina M.
Published: March 2011

Laminated sandstones from the 2.9 Ga Pongola Supergroup, South Africa, were characterized using micro‐Raman spectral imaging to elucidate the origin of the mineral components. These sandstones were formed in a paleoenvironment conducive to sustaining life and contain compelling features reminiscent of ancient microbial mat remains. Most sedimentary rocks of this age have been altered over time through metamorphism and weathering, obscuring any original biologic or mineralogic signatures. Therefore, determination of the exact formation mechanism for biologically associated features is often precluded, resulting in large gaps in our understanding of early life and Earth's early habitable environments. The results of the Raman analyses show that the parallel to bedding laminations in these rocks consist of elongated muscovite grains that are intimately associated with anatase, rutile, goethite, and graphitic carbon. The morphology, orientation, and intimate associations of the component mineral assemblage in the laminations suggest that physiochemical events, such as weathering, low‐grade metamorphism, or hydrothermal fluids, were also key in their formation and influenced their geochemical makeup. Given the complicated histories of ancient sedimentary rocks, the use of techniques such as micro‐Raman spectroscopy is crucial in determining the origins of sedimentary structures that might otherwise be misinterpreted. Copyright © 2011 John Wiley & Sons, Ltd.
Improvement of water transport mechanisms during potato drying by applying ultrasound
Authors: Ozuna César , Cárcel Juan A , García‐Pérez José V , Mulet Antonio
Published: March 2011

BACKGROUND:The drying rate of vegetables is limited by internal moisture diffusion and convective transport mechanisms. The increase of drying air temperature leads to faster water mobility; however, it provokes quality loss in the product and presents a higher energy demand. Therefore, the search for new strategies to improve water mobility during convective drying constitutes a topic of relevant research. The aim of this work was to evaluate the use of power ultrasound to improve convective drying of potato and quantify the influence of the applied power in the water transport mechanisms.

RESULTS:Drying kinetics of potato cubes were increased by the ultrasonic application. The influence of power ultrasound was dependent on the ultrasonic power (from 0 to 37 kW m−3), the higher the applied power, the faster the drying kinetic. The diffusion model considering external resistance to mass transfer provided a good fit of drying kinetics. From modelling, it was observed a proportional and significant (P< 0.05) influence of the applied ultrasonic power on the identified kinetic parameters: effective moisture diffusivity and mass transfer coefficient.

CONCLUSIONS:The ultrasonic application during drying represents an interesting alternative to traditional convective drying by shortening drying time, which may involve an energy saving concerning industrial applications. In addition, the ultrasonic effect in the water transport is based on mechanical phenomena with a low heating capacity, which is highly relevant for drying heat sensitive materials and also for obtaining high‐quality dry products. Copyright © 2011 Society of Chemical Industry
Enhanced magnetic cell labeling efficiency using –NH2 coated MPIOs
Authors: Tang Kevin S. , Shapiro Erik M.
Published: March 2011

Strategies have been developed for labeling cells with micron sized iron oxide particles (MPIOs) for in vivo visualization of cells by magnetic resonance imaging. Although this approach is well established and has a variety of applications, current protocols employ long labeling times. It has been previously demonstrated that incubation of dextran coated iron oxide nanoparticles with positively charged transfection agents, such as poly‐L‐lysine increases labeling efficiency. Therefore, we sought to ascertain whether preincubating MPIOs with various quantities of poly‐L‐lysine would similarly enhance the rate of magnetic cell labeling. This was also tested against an NH2 functionalized, commercially available MPIO. Indeed, we demonstrate significantly increased rate of magnetic cell labeling with MPIOs previously incubated with varying amounts of poly‐L‐lysine, with robust intracellular labeling at 2 hours. Yet the most robust labeling was achieved with the MPIO‐NH2. Interestingly, even for particle formulations which still had negative zeta potential, enhancement of magnetic cell labeling was achieved. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Two‐dimensional phase cycled reconstruction for inherent correction of echo‐planar imaging nyquist artifacts
Authors: Chen Nan‐Kuei , Avram Alexandru V. , Song Allen W.
Published: March 2011

The inconsistency of k‐space trajectories results in Nyquist artifacts in echo‐planar imaging (EPI). Traditional techniques often only correct for phase errors along the frequency‐encoding direction (one‐dimensional correction), which may leave significant residual artifacts, particularly for oblique‐plane EPI or in the presence of cross‐term eddy currents. As compared with one‐dimensional correction, two‐dimensional (2D) phase correction can be much more effective in suppressing Nyquist artifacts. However, most existing 2D correction methods require reference scans and may not be generally applicable to different imaging protocols. Furthermore, EPI reconstruction with these 2D phase correction methods is susceptible to error amplification due to subject motion. To address these limitations, we report an inherent and general 2D phase correction technique for EPI Nyquist removal. First, a series of images are generated from the original dataset, by cycling through different possible values of phase errors using a 2D reconstruction framework. Second, the image with the lowest artifact level is identified from images generated in the first step using criteria based on background energy in sorted and sigmoid‐weighted signals. In this report, we demonstrate the effectiveness of our new method in removing Nyquist ghosts in single‐shot, segmented and parallel EPI without acquiring additional reference scans and the subsequent error amplifications. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Quantitative lithium magnetic resonance spectroscopy in the normal human brain on a 3 T clinical scanner
Authors: Smith Fiona E. , Cousins David A. , Thelwall Peter E. , Ferrier I. Nicol , Blamire Andrew M.
Published: March 2011

Lithium (Li) is a core for many neuropsychiatric conditions. The safe serum range of Li treatment is narrow, and regular monitoring by blood test is required, although serum levels are thought to be a poor indicator of Li concentration in the brain itself. Brain Li concentration can be measured by magnetic resonance spectroscopy. However, little data exist in the healthy human brain, and there are no studies of the relaxation properties of brain 7Li at 3 T. Here, 11 healthy male subjects were prescribed Li over a period of 11 days. In seven subjects, the in vivo T1 of 7Li was measured to be 2.1 ± 0.7 s. In the remaining subjects, spectroscopic imaging (1D) yielded a mean brain 7Li concentration of 0.71 ± 0.1 mM, with no significant difference between gray and white matter. Mean serum concentration was 0.9 ± 0.16 mM, giving a mean brain/serum ratio of 0.78 ± 0.26. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Technical Note: A note on the selection of the penalty parameter for discontinuous Galerkin finite element schemes
Authors: Ainsworth Mark , Rankin Richard
Published: March 2011

We obtain a computable lower bound on the value of the interior penalty parameters sufficient for the existence of a unique discontinuous Galerkin finite element approximation of a second order elliptic problem. The bound obtained is valid for meshes containing an arbitrary number of hanging nodes and elements of arbitrary nonuniform polynomial order. © 2011 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2011
A new method for two dimensional hyperbolic problems in semi‐unbounded irregular domains
Authors: Bratsos A. G.
Published: March 2011

Anewmethod called the full rational differential quadrature method is presented to deal with two dimensional linear and nonlinear hyperbolic problems in semi‐unbounded irregular domains. The spacial and temporal discretizations are both implemented by the rational differential quadrature method (RDQM). The RDQM, proven to be A‐stable (Chen and Tanaka, Comput Mech 28 (2002) 331–338) in the temporal discretization, is much more efficient than the finite difference schemes widely used in earlier works. In addition, the irregular boundary conditions are treated by the direct expansion method(DEM). Numerical experiments show that the present method is of high efficiency and easy to implement. © 2011Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2011
Cutaneous hematologic disorders in children
Authors: Boccara Olivia , Blanche Stéphane , de Prost Yves , Brousse Nicole , Bodemer Christine , Fraitag Sylvie
Published: March 2011

Background

To determine and list the clinical and pathological features of cutaneous hematologic diseases in childhood.

Procedure

We retrospectively analyzed the data for 51 patients up to 15 years of age, who presented with primary cutaneous hematologic disorders according to the WHO‐EORTC classification, at Necker‐Enfants Malades Hospital, Paris, France, over a 17‐year period. The cases were classified into the following diagnostic categories: CD30+ T‐cell lymphoproliferative disorders (24) all consisting of lymphomatoid papulosis (LyP, 24), lymphoblastic lymphoma (LL, 7), acute leukemias (AL, 7), mycosis fungoides (MF, 5), Epstein–Barr virus‐related lymphoproliferative disorders (EBV‐related LPD, 5), T/NK‐cell lymphoma, nasal type (1), γ/δ T‐cell lymphoma (1), and panniculitis‐like T‐cell lymphoma (1).

Results

We encountered a majority of LyP. No secondary lymphoma was found in LyP patients with a median follow‐up of 8 years. 29% and 80% of LyP and MF patients, respectively, presented with pityriasis lichenoides chronica (PLC) before onset of disease. Owing to a frequently misleading clinicopathological presentation, MF patients were first underdiagnosed. Clinicopathological features of LL and AL were highly stereotypical, leading to the diagnosis being suspected and confirmed more promptly. In the latter patients and in EBV‐related LPD patients, skin lesions usually led to the discovery of systemic disease.

Conclusion

Distribution of cutaneous hematologic diseases seems to be different in adults and in children aged <15‐year old. PLC was strongly correlated with MF and LyP. Physicians must be made aware of the stereotypical clinical presentations of LL and AL to allow prompt diagnosis and treatment. Pediatr Blood Cancer 2012; 58: 226–232. © 2011 Wiley Periodicals, Inc.
Model predicted Down syndrome detection rates for nuchal translucency screening in twin pregnancies
Authors: Maymon Ron , Rosen Hadar , Baruchin Ohad , Herman Arie , Cuckle Howard
Published: March 2011

Objective

To estimate the Down syndrome detection rate for nuchal translucency (NT) screening in twins when fetus‐specific risk allows for between‐fetus NT correlation.

Methods

The between‐fetus correlation coefficient of log NT, in multiples of the median (MoM), was estimated from a series of 977 unaffected twins scanned at a single centre. Results were expressed in multiples of the normal median using a curve derived from 515 unaffected singleton pregnancies at the same centre. A screening result was classified as positive if the risk for at least one fetus exceeded the cut‐off. Detection rates were estimated for a fixed 1–5% false‐positive rate, at different gestational weeks, separately for risk calculation using an algorithm which takes account of between‐fetus NT correlation or not.

Results

The correlation coefficient in unaffected pregnancies was 0.43 (P < 0.0001) and estimated to be 0.23 and 0.11 in discordant and concordant twins. At 12 weeks of gestation, the model predicted detection rate for a 3% false‐positive rate was 68% when between‐fetus correlation is not taken into account, increasing to 73% when it is applied. Similarly, for other false‐positive rates and gestational weeks there was a predicted 4–6% increase in detection.

Conclusion

Using a fetus‐specific Down syndrome risk algorithm leads to a worthwhile increase in detection. Copyright © 2011 John Wiley & Sons, Ltd.