bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐transplant Burkitt lymphoma is a more aggressive and distinct form of post‐transplant lymphoproliferative disorder
Authors: Picarsic Jennifer , Jaffe Ronald , Mazariegos George , Webber Steve A. , Ellis Demetrius , Green Michael D. , Reyes‐Múgica Miguel
Published: March 2011

BACKGROUND:

Although the literature reports a low incidence of Burkitt lymphoma (BL) as a post‐transplant lymphoproliferative disorder (PTLD), this entity appears to be different from other monomorphic PTLDs (M‐PTLDs), both in its aggressive clinical presentation and its distinct pathologic profile.

METHODS:

Patients with BL, diagnosed in the post‐transplant setting, (patients aged ≤18 years) were retrieved from the pathology archives at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center from 1982 to 2010. Clinical outcomes were obtained along with pathologic review.

RESULTS:

Twelve patients with pediatric BL in the post‐transplant setting (9 boys, 3 girls) were retrieved. The patients displayed a monomorphic population of small to intermediate‐sized, noncleaved, lymphoid elements with a “starry‐sky” pattern. The immunophenotype for patients available to the study was CD20+ (n = 9/10), CD10+ (n = 8/8), bcl‐6+ (n = 11/11), with a near 100% Ki‐67/MIB‐1 proliferation index (n = 7/7), and negative for TdT (n = 7/7). Most pretransplant Epstein‐Barr virus titers were negative (n = 8/10), with post‐transplant titers positive in all tested patients (n = 11), and with positive Epstein‐Barr–encoded RNA in situ hybridization in most cases (n = 9/11). The median time from transplantation to diagnosis was 52 months (range, 6‐107 months). Nine patients were currently alive after immediate antineoplastic chemotherapy, with median disease‐free time of 93 months from diagnosis (range, 2‐199 months).

CONCLUSIONS:

BL‐PTLD had a higher Epstein‐Barr virus incidence compared with sporadic and immunodeficiency‐associated BL and represented a distinct monomorphic PTLD. Although some M‐PTLDs can be managed less aggressively with decreased immunosuppression alone, immediate lymphoma‐specific chemotherapy was associated with a favorable outcome and was strongly recommended. Cancer 2011;. © 2011 American Cancer Society.
Radiotherapy and surgery—An indispensable duo in the treatment of retroperitoneal sarcoma
Authors: Van De Voorde Lien , Delrue Louke , van Eijkeren Marc , De Meerleer Gert
Published: March 2011

The authors undertook a systematic review to designate the role that radiotherapy (RT) might play in the treatment of retroperitoneal sarcomas. Correlating with recent literature, the objective of this review was to evaluate whether there was enough evidence for the authors to develop an institutional treatment protocol concerning the use of RT in the treatment of retroperitoneal sarcoma. Furthermore, this was a call for surgeons to talk to radiation oncologists before performing surgery. The 2 objectives of this review were: 1) to determine the benefit of RT in terms of local control and/or survival in the treatment of retroperitoneal sarcomas and 2) to discover the optimal timing of RT in the treatment sequence. A computerized literature search was performed in the PubMed database, the Cochrane Library database, and reference lists; and journals also were searched by hand to identify all retrospective and prospective reports published since 1998 relating to RT treatment of adult retroperitoneal sarcoma. Mainly, analyses were sought that were based on a 5‐year local control rate (LCR), 5‐year disease‐free survival, and 5‐year overall survival (OS). If only 2 years follow‐up were available, then the authors also noted this outcome. Toxicity data were collected and analyzed separately. The synthesis of the literature was based on 9 prospectively nonrandomized studies and 10 retrospective studies that, together, reviewed a total of 1426 patients. The 5‐year LCR varied from 27% to 62%, and the results from other reports fell in between those values. The 5‐year OS rate ranged from 12% to 90%, and complete resection and tumor grade were the most important prognostic factors in most studies. This review resulted in 7 recommendations concerning the use of RT in the treatment of retroperitoneal sarcoma. The authors concluded that there is good evidence from multiple single‐institutions studies that RT improves the LCR in patients with retroperitoneal sarcoma. Until now, there has not been a translation of this approach into survival benefit. The current results indicated that preoperative external‐beam RT followed by radical surgery seems to be the preferred sequence, and adding intraoperative RT is a safe procedure for dose escalation in the upper abdomen. Cancer 2011;. © 2011 American Cancer Society.
Polydactyly: How many disorders and how many genes? 2010 update
Authors: Biesecker Leslie G.
Published: March 2011

Limb development is clinically and biologically important. Polydactyly is common and caused by aberrant anterior–posterior patterning. Human disorders that include polydactyly are diverse. To facilitate an understanding of the biology of limb development, cataloging the genes that are mutated in patients with polydactyly would be useful. In 2002, I characterized human phenotypes that included polydactyly. Subsequently, many advances have occurred with refinement of clinical entities and identification of numerous genes. Here, I update human polydactyly entities by phenotype and mutated gene. This survey demonstrates phenotypes with overlapping manifestations, genetic heterogeneity, and distinct phenotypes generated from mutations in single genes. Among 310 clinical entities, 80 are associated with mutations in 99 genes. These results show that knowledge of limb patterning genetics is improving rapidly. Soon, we will have a comprehensive toolkit of genes important for limb development, which will lead to regenerative therapies for limb anomalies. Developmental Dynamics 240:931–942, 2011. © 2011 Wiley‐Liss, Inc.
Establishment of conditional reporter mouse lines at ROSA26 locus for live cell imaging
Authors: Abe Takaya , Kiyonari Hiroshi , Shioi Go , Inoue Ken‐Ichi , Nakao Kazuki , Aizawa Shinichi , Fujimori Toshihiko
Published: March 2011

A series of conditional reporter mouse lines were established in which specific organelles were labeled with fluorescent proteins. Subcellular localization and intensity of 28 fluorescent fusion‐protein constructs were surveyed in cell lines, and 16 constructs then were selected to generate mouse lines. The fusion cDNAs were inserted into the ROSA26 genomic locus next to the stop sequences flanked with loxP so that fluorescent proteins were expressed under the ubiquitous ROSA26 transcriptional machinery when the loxP sequences were recombined with Cre. The subcellular localization and intensity of the fusion product in each reporter mouse line were examined by ubiquitously expressing them in E7.5 embryos. Twelve reporter lines, that mark nucleus, mitochondria, Golgi apparatus, plasma membrane, microtubule, actin filament, and focal adhesion, were found suitable for live imaging. Distinct double staining was demonstrated for nucleus and plasma membrane or Golgi apparatus; clear time‐lapse live images were obtained for nucleus and plasma membranes; conditional expression was confirmed on Lyn‐Venus and H2B‐mCherry lines in notochord with Not‐Cre. genesis, 49:579–590, 2011. © 2011 Wiley‐Liss, Inc.
Photolysis of Hi‐CO Nitrogenase – Observation of a Plethora of Distinct CO Species Using Infrared Spectroscopy
Authors: Yan Lifen , Dapper Christie H. , George Simon J. , Wang Hongxin , Mitra Devrani , Dong Weibing , Newton William E. , Cramer Stephen P.
Published: March 2011

Fourier‐transform infrared‐spectroscopy (FT‐IR) was used to study the photochemistry of CO‐inhibited Azotobacter vinelandii Mo nitrogenase using visible light at cryogenic temperatures. The FT‐IR difference spectrum of photolyzed hi‐CO at 4 K comprises negative bands at 1973 cm–1 and 1679 cm–1 together with positive bands at 1711 cm–1, 2135 and 2123 cm–1. The negative bands are assigned to a hi‐CO state that comprises 2 metal‐bound CO ligands, one terminally bound, and one bridged and/or protonated species. The positive band at 1711 cm–1 is assigned to a lo‐CO product with a single bridged and/or protonated metal‐CO group. We term these species “Hi‐1” and “Lo‐1”, respectively. The high‐energy bands are assigned to a liberated CO trapped in the protein pocket. Warming results in CO recombination, and the temperature dependence of the recombination rate yields an activation energy of 4 kJ mol–1. Two α‐H195 variant enzymes yielded additional signals. Asparagine substitution, α‐H195N, gives a spectrum containing 2 negative “Hi‐2” bands at 1936 and 1858 cm–1 with a positive “Lo‐2” band at 1780 cm–1, while glutamine substitution, α‐H195Q, produces a complex spectrum that includes a third CO species, with negative “Hi‐3” bands at 1938 and 1911 cm–1 and a positive feature “Lo‐3” band at 1921 cm–1. These species can be assigned to a combination of terminal, bridged, and possibly protonated CO groups bound to the FeMo cofactor active site. The proposed structures are discussed in terms of both CO inhibition and the mechanism nitrogenase catalysis. Given the intractability of observing nitrogenase intermediates by crystallographic methods, IR‐monitored photolysis appears to be a promising and information‐rich probe of nitrogenase structure and chemistry.
Ligand‐Free Pd‐Catalyzed Carbonylative Cross‐Coupling Reactions under Atmospheric Pressure of Carbon Monoxide: Synthesis of Aryl Ketones and Heteroaromatic Ketones
Authors: Li Hongling , Yang Min , Qi Yanxing , Xue Jijun
Published: March 2011

The carbonylative Suzuki cross‐coupling reactions of boronic acids with aryl iodides catalyzed by Pd2(dba)3 as a ligand‐free catalyst under atmospheric pressure of carbon monoxide has been firstly developed. Under mild reaction conditions, a broad range of aryl/heteroaryl iodides and aryl/heteroaryl boronic acids were selectively coupled to afford the corresponding diaryl ketones in good to excellent yields at low catalyst loadings (0.05 to 2 mol‐%). Moreover, the catalyst can also be recycled.
Silicon Lewis Acid Catalyzed [3+2] Cycloaddition Reactions of Hydrazones/Cyclopentadiene: Mild Access to Pyrazolidine Derivatives
Authors: Zamfir Alexandru , Schenker Sebastian , Bauer Walter , Clark Timothy , Tsogoeva Svetlana B.
Published: March 2011

A first and fairly mild metal‐free catalytic route was developed for the [3+2] cycloadditions of different N‐acylhydrazones to cyclopentadiene, providing the synthetically andbiologically important five‐membered cyclic compounds pyrazolidines. The reaction was successfully conducted in high yields (up to 99 %) with high diastereoselectivities (up to 98:2 dr) by using catalytic amounts of TMSOTf (trimethylsilyl triflate) as a readily available Lewis acidic catalyst. The experimental findings were supported by DFT calculations of the reaction mechanism. The theoretical and experimental diastereomeric excess values show good agreement, rendering the computations an efficient tool for predicting the selectivities in these and related reactions.
The brain tumor microenvironment
Authors: Charles Nikki A. , Holland Eric C. , Gilbertson Richard , Glass Rainer , Kettenmann Helmut
Published: March 2011

High‐grade brain tumors are heterogeneous with respect to the composition of bona fide tumors cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell‐like capacity. The stem‐like cells may be the cells of origin for tumor relapse. However, the tumor‐associated parenchymal cells—such as vascular cells, microglia, peripheral immune cells, and neural precursor cells—also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact and signaling pathways known for these types of cell–cell communication. The tumor‐vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem‐like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non‐neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural stem and progenitor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. © 2011 Wiley‐Liss, Inc.
Progenitors in the adult cerebral cortex: Cell cycle properties and regulation by physiological stimuli and injury
Authors: Simon Christiane , Götz Magdalena , Dimou Leda
Published: March 2011

The adult brain parenchyma contains a widespread population of progenitors generating different cells of the oligodendrocyte lineage such as NG2+ cells and some mature oligodendrocytes. However, it is still largely unknown how proliferation and lineage decisions of these progenitors are regulated. Here, we first characterized the cell cycle length, proliferative fraction, and progeny of dividing cells in the adult cerebral cortex and then compared these proliferation characteristics after two distinct stimuli, invasive acute brain injury and increased physiological activity by voluntary physical exercise. Our data show that adult parenchymal progenitors have a very long cell cycle due to an extended G1 phase, many of them can divide at least twice and only a limited proportion of the progeny differentiates into mature oligodendrocytes. After stab wound injury, however, many of these progenitors re‐enter the cell cycle very fast, suggesting that the normally long G1 phase is subject to regulation and can be abruptly shortened. In striking contrast, voluntary physical exercise shows the opposite effect with increased exit of the cell cycle followed by an enhanced and fast differentiation into mature oligodendrocytes. Taken together, our data demonstrate that the endogenous population of adult brain parenchymal progenitors is subject to profound modulation by environmental stimuli in both directions, either faster proliferation or faster differentiation. © 2011 Wiley‐Liss, Inc.
Activation of interferon signaling pathways in spinal cord astrocytes from an ALS mouse model
Authors: Wang Rengang , Yang Bo , Zhang Dongxian
Published: March 2011

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting predominantly motor neurons. Recent studies suggest that the disease progression of ALS is non‐cell‐autonomous, although the interaction between neurons and glial cells in different disease stages is not entirely clear. Here, we demonstrate that the interferon (IFN) signaling pathway is activated in human SOD1(G93A) transgenic mice, a rodent model of ALS. IFN‐stimulated genes (ISGs) increased in the spinal cord of SOD1(G93A) mice at a presymptomatic age. In addition, the up‐regulated ISGs, and most likely their transcriptional activators, were found specifically in astrocytes surrounding motor neurons, suggesting that IFN signaling in astrocytes was triggered by specific pathologic changes in motor neurons. Furthermore, induction of ISGs in cultured astrocytes was highly sensitive to IFN, especially Type I IFN. ISGs in astrocytes were activated specifically by endoplasmic reticulum stress‐induced neurodegeneration in vitro, implicating a similar process in the presymptomatic stage of SOD1 mutant mice. Finally, reduction or deletion of IFNα receptor 1 inhibited IFN signaling and increased the life‐span of SOD1(G93A) mice. Thus, the activation of IFN signaling pathways represents an early “dialogue” between motor neurons and astrocytes in response to pathological changes in ALS. © 2011 Wiley‐Liss, Inc.
Impact of aquaporin‐4 channels on K+ buffering and gap junction coupling in the hippocampus
Authors: Strohschein Susan , Hüttmann Kerstin , Gabriel Siegrun , Binder Devin K. , Heinemann Uwe , Steinhäuser Christian
Published: March 2011

Aquaporin‐4 (AQP4) is the main water channel in the brain and primarily localized to astrocytes where the channels are thought to contribute to water and K+ homeostasis. The close apposition of AQP4 and inward rectifier K+ channels (Kir4.1) led to the hypothesis of direct functional interactions between both channels. We investigated the impact of AQP4 on stimulus‐induced alterations of the extracellular K+ concentration ([K+]o) in murine hippocampal slices. Recordings with K+‐selective microelectrodes combined with field potential analyses were compared in wild type (wt) and AQP4 knockout (AQP4−/−) mice. Astrocyte gap junction coupling was assessed with tracer filling during patch clamp recording. Antidromic fiber stimulation in the alveus evoked smaller increases and slower recovery of [K+]o in the stratum pyramidale of AQP4−/− mice indicating reduced glial swelling and a larger extracellular space when compared with control tissue. Moreover, the data hintat an impairment of the glial Na+/K+ ATPase in AQP4‐deficient astrocytes. In a next step, we investigated the laminar profile of [K+]o by moving the recording electrode from the stratum pyramidale toward the hippocampal fissure. At distances beyond 300 μm from the pyramidal layer, the stimulation‐induced, normalized increases of [K+]o in AQP4−/− mice exceeded the corresponding values of wt mice, indicating facilitated spatial buffering. Astrocytes in AQP4−/− mice also displayed enhanced tracer coupling, which might underlie the improved spatial re‐ distribution of [K+]o in the hippocampus. These findings highlight the role of AQP4 channels in the regulation of K+ homeostasis. © 2011 Wiley‐Liss, Inc.
Influence of nanofluids on mixed convective heat transfer over a horizontal backward‐facing step
Authors: Mohammed H.A. , Al‐aswadi A.A. , Abu‐Mulaweh H.I. , Shuaib N.H.
Published: March 2011

Predictions are reported for laminar mixed convection using various types of nanofluids over a horizontal backward‐facing step in a duct, in which the upstream wall and the step are considered adiabatic surfaces, while the downstream wall from the step is heated to a uniform temperature that is higher than the inlet fluid temperature. The straight wall that forms the other side of the duct is maintained at constant temperature equivalent to the inlet fluid temperature. Eight different types of nanoparticles, Au, Ag, Al2O3, Cu, CuO, diamond, SiO2, and TiO2, with 5% volume fraction are used. The conservation equations along with the boundary conditions are solved using the finite volume method. Results presented in this paper are for a step height of 4.9 mm and an expansion ratio of 1.942, while the total length in the downstream of the step is 0.5 m. The Reynolds number is in the range of 75 ≤ Re ≤ 225. The downstream wall was fixed at a uniform wall temperature in the range of 0 ≤ ΔT ≤ 30 °C which is higher than the inlet flow temperature. Results reveal that there is a primary recirculation region for all nanofluids behind the step. It is noticed that nanofluids without secondary recirculation region have a higher Nusselt number and it increases with Prandtl number decrement. On the other hand, nanofluids with secondary recirculation regions are found to have a lower Nusselt number. Diamond nanofluid has the highest Nusselt number in the primary recirculation region, while SiO2 nanofluid has the highest Nusselt number downstream of the primary recirculation region. The skin friction coefficient increases as the temperature difference increases and the Reynolds number decreases. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20344
Hypothyroidism following childhood cancer therapy–an under diagnosed complication
Authors: Brabant Georg , Toogood Andrew A. , Shalet Stephen M , Frobisher Clare , Lancashire Emma R , Reulen Raoul C , Winter David L , Hawkins Michael M.
Published: March 2011

To determine the prevalence of hypothyroidism amongst most adult survivors of childhood cancer in Britain using the British Childhood Cancer Survivor Study (BCCSS). The BCCSS is a population based cohort of individuals diagnosed with childhood cancer between 1940 and 1991 and who survived at least 5 years from diagnosis (n = 17,981). 10483, 71% of those survivors aged at least 16 years, returned a completed questionnaire, which asked if hypothyroidism had been diagnosed. Of the whole cohort, 7.7% reported hypothyroidism with the highest risk among patients treated for Hodgkin's disease (HD) (19.9%), CNS neoplasms (15.3%), Non‐Hodgkin's lymphoma (6.2%) and leukaemia (5.2%). Survivors were more likely to develop hypothyroidism if they had received radiotherapy for HD (p = 0.0001) or a CNS neoplasm (p < 0.00005) but not leukaemia (p = 0.3). In these three patient groups, the frequency of hypothyroidism was similar in men and women. Survivors of irradiated CNS tumours reported a prevalence of hypothyroidism, which was substantially lower if discharged to primary care compared with being on hospital follow‐up and which declined substantially with increased follow‐up in both primary care (p = 0.004) and hospital follow‐up (p = 0.023) settings. Hypothyroidism is a common finding amongst adult survivors of childhood malignancy. The substantial differences in reported hypothyroidism prevalence after irradiated CNS neoplasms suggests substantial under‐diagnosis, which increased with increased follow‐up, and which increased among those followed‐up in primary care compared with hospital settings.
Breast cancer and age in Black and White women in South East England
Authors: Jack Ruth H. , Davies Elizabeth A. , Møller Henrik
Published: March 2011

Black women have lower age‐standardized breast cancer incidence rates than White women in the United Kingdom. However, little is known about such differences in risk in separate age groups. Records on female residents of South East England diagnosed with breast cancer between 1998 and 2003 were extracted from the Thames Cancer Registry database. Age‐specific incidence rates were calculated for each 5‐year age group using 2001 Census population data for White, Black Caribbean and Black African women. Black Caribbean and Black African breast cancer patients were younger than both the White patients and those with no ethnicity recorded. Black Caribbean and Black African women in the population also had a younger age profile than White women. The computed age‐specific incidence rates in women aged under 50 were similar in the different ethnic groups, whereas in women aged 50 and over White women had higher rates. The younger age of Black Caribbean and Black African breast cancer patients in South East England reflects the younger age of these populations, rather than an increased risk of disease at younger ages.
Significant associations of prostate cancer susceptibility variants with survival in patients treated with androgen‐deprivation therapy
Authors: Bao Bo‐Ying , Pao Jiunn‐Bey , Huang Chun‐Nung , Pu Yeong‐Shiau , Chang Ta‐Yuan , Lan Yu‐Hsuan , Lu Te‐Ling , Lee Hong‐Zin , Chen Lu‐Min , Ting Wen‐Chien , Hsieh Chi‐Jeng , Huang Shu‐Pin
Published: March 2011

Androgen‐deprivation therapy (ADT) is the most common therapy for advanced prostate cancer, but the prognosis significantly differs among individuals. In this study, we evaluated recently identified 19 prostate cancer susceptibility variants as prognostic predictors for the survival after ADT. A total of 601 prostate cancer patients treated with ADT were enrolled in this study cohort. The prognostic significance of the prostate cancer risk variants on disease progression, prostate cancer‐specific mortality (PCSM) and all‐cause mortality (ACM) after ADT were assessed by Kaplan–Meier analysis and Cox regression model. Two polymorphisms, rs16901979 and rs7931342, were significantly associated with PCSM (p = 0.005 for rs16901979 and p = 0.038 for rs7931342), and rs16901979 was also associated with ACM (p = 0.003) following ADT. Although the effect of rs7931342 was attenuated after controlling for other known clinical prognostic factors, rs16901979 remained a significant predictor for PCSM and ACM after ADT (p = 0.002). Moreover, the addition of the rs16901979 status in current clinical staging system further enhanced the risk prediction on PCSM and ACM particularly for the high‐risk patients with distant metastasis (p < 0.017). In conclusion, this is the first study showing that prostate cancer risk variants, such as rs16901979, might improve outcome prediction following ADT, thus allowing identification of high‐risk patients who might benefit from appropriate adjuvant therapy.
Increased frequency of 20q gain and copy‐neutral loss of heterozygosity in mismatch repair proficient familial colorectal carcinomas
Authors: Middeldorp A. , van Eijk R. , Oosting J. , Forte G.I. , van Puijenbroek M. , van Nieuwenhuizen M. , Corver W.E. , Ruano D. , Caldes T. , Wijnen J. , Morreau H. , van Wezel T.
Published: March 2011

Many hereditary nonpolyposis colorectal cancers (CRCs) cannot be explained by Lynch syndrome. Other high penetrance genetic risk factors are likely to play a role in these mismatch repair (MMR)‐proficient CRC families. Because genomic profiles of CRC tend to vary with CRC susceptibility syndromes, our aim is to analyze the genomic profile of MMR‐proficient familial CRC to obtain insight into the biological basis of MMR‐proficient familial CRC. We studied 30 MMR‐proficient familial colorectal carcinomas, from 15 families, for genomic aberrations, including gains, physical losses, and copy‐neutral loss of heterozygosity LOH (cnLOH) using SNP array comparative genomic hybridization. In addition, we performed somatic mutation analysis for KRAS, BRAF, PIK3CA and GNAS. The frequency of 20q gain (77%) is remarkably increased when compared with sporadic CRC, suggesting that 20q gain is involved in tumor progression of familial CRC. There is also a significant increase in the frequency of cnLOH and, as a consequence, a reduced frequency of physical loss compared with sporadic CRC. The most frequent aberrations observed included gains of 7p, 7q, 8q, 13q, 20p and 20q as well as physical losses of 17p, 18p and 18q. Most of these changes are also observed in sporadic CRC. Mutations in KRAS were identified in 37% of the MMR‐proficient CRCs, and mutations in BRAF were identified in 16%. No mutations were identified in PIK3CA or chromosome 20 candidate gene GNAS. We show that the patterns of chromosomal instability of MMR‐proficient familial CRC are clearly distinct from those from sporadic CRC. Both the increased gain on chromosome 20 and the increased levels of cnLOH suggest the presence of yet undiscovered germline defects that can, in part, underlie the cancer risk in these families.
Neuroglobin, estrogens, and neuroprotection
Authors: De Marinis Elisabetta , Marino Maria , Ascenzi Paolo
Published: March 2011

Globins have been found in glial cells and neurons of invertebrates and vertebrates. The first nerve globin has been recognized in the nerve cord of the polychaete annelid Aphrodite aculeata in 1872. In some invertebrates, the nerve globin reaches a millimolar concentration which is likely sufficient to sustain the aerobic metabolism and thus the excitability of the nervous system. In 2000, the first vertebrate nerve globin, named neuroglobin (Ngb), has been identified in neuronal tissues of mice and humans. In contrast to invertebrate nerve globins, the concentration of Ngb, the prototype of vertebrate nerve globins, is low (μM), reaching a maximum of 100 μM in retina cells. Therefore, Ngb appears unlikely to act primarily as an O2 buffer and to facilitate O2 diffusion to the mitochondria. Indeed, Ngb has been hypothesized to catalyze the formation/decomposition of reactive nitrogen and/or oxygen species and to be part of intracellular signaling pathways enhancing cell survival. Here, we report that neuronal Ngb levels are strongly induced by the steroid hormone 17β‐estradiol. Furthermore, Ngb participates to mechanisms involved in 17β‐estradiol‐induced protective effects against H2O2‐induced neurotoxicity. © 2011 IUBMB IUBMB Life, 63(3): 140–145, 2011
The refined structure of functional unit h of keyhole limpet hemocyanin (KLH1‐h) reveals disulfide bridges
Authors: Jaenicke Elmar , Büchler Kay , Decker Heinz , Markl Jürgen , Schröder Gunnar F
Published: March 2011

Hemocyanins are multimeric oxygen‐transport proteins in the hemolymph of many arthropods and mollusks. The overall molecular architecture of arthropod and molluscan hemocyanin is very different, although they possess a similar binuclear type 3 copper center to bind oxygen in a side‐on conformation. Gastropod hemocyanin is a 35 nm cylindrical didecamer (2 × 10‐mer) based on a 400 kDa subunit. The latter is subdivided into eight paralogous “functional units” (FU‐a to FU‐h), each with an active site. FU‐a to FU‐f contribute to the cylinder wall, whereas FU‐g and FU‐h form the internal collar complex. Atomic structures of FU‐e and FU‐g, and a 9 Å cryoEM structure of the 8 MDa didecamer are available. Recently, the structure of keyhole limpet hemocyanin FU‐h (KLH1‐h) was presented as a Cα‐trace at 4 Å resolution. Unlike the other seven FU types, FU‐h contains an additional C‐terminal domain with a cupredoxin‐like fold. Because of the resolution limit of 4 Å, in some loops, the course of the protein backbone could not be established with high certainty yet. Here, we present a refined atomic structure of FU‐h (KLH1‐h) obtained from low‐resolution refinement, which unambiguously establishes the course of the polypeptide backbone and reveals the disulfide bridges as well as the orientation of bulky amino acids. © 2011 IUBMB IUBMB Life, 63(3): 183–187, 2011
Fast and long term lipid droplet tracking with CARS microscopy
Authors: Jüngst Christian , Winterhalder Martin J. , Zumbusch Andreas
Published: March 2011

Photobleaching of organic fluorophores commonly used in fluorescence microscopy puts a limit to the number of images which can be acquired. Label‐free imaging techniques therefore offer advantages both for rapid image acquisition and for long–term observations. CARS microscopy is a label‐free imaging technique offering molecule specific contrast. Here we demonstrate that CARS microscopy allows video‐rate tracking of intracellular transport of lipid droplets, but also continuous long‐term observation of cells over several hours. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spata4 promotes osteoblast differentiation through Erk-activated Runx2 pathway
Authors: Wang Xiaoyan , Harimoto Kenichi , Liu Jing , Guo Junwei , Hinshaw Stephen , Chang Zhijie , Wang Zhao
Published: March 2011

The spermatogenesis associated 4 gene (Spata4, previously named TSARG2) was demonstrated to participate in spermatogenesis. Here we report that Spata4 is expressed in osteoblasts and that overexpression of Spata4 accelerates osteoblast differentiation and mineralization in MC3T3-E1 cells. We found that Spata4 interacts with p-Erk1/2 in the cytoplasm and that overexpression of Spata4 enhances the phosphorylation of Erk1/2. Intriguingly, we observed that Spata4 increases the transcriptional activity of Runx2, a critical transcription factor regulating osteoblast differentiation. We showed that Spata4-activated Runx2 is through the activation of Erk1/2. Consistent with this observation, we found that overexpression of Spata4 increases the expression of osteoblastic marker genes, including osteocalcin (Ocn), Bmp2, osteopontin (Opn), type 1 collagen, osterix (Osx), and Runx2. We concluded that Spata4 promotes osteoblast differentiation and mineralization through the Erk-activated Runx2 pathway. Our findings provided new evidence that Spata4 plays a role in regulation of osteoblast differentiation. © 2011 American Society for Bone and Mineral Research
Down‐regulation of BMI‐1 cooperates with artemisinin on growth inhibition of nasopharyngeal carcinoma cells
Authors: Wu Jing , Hu Dong , Yang Guang , Zhou Junyi , Yang Changfu , Gao Yun , Zhu Zhenyu
Published: March 2011

Artemisinin and its derivatives are well known antimalaria drugs, particularly useful for the treatment of infection of Plasmodium falciparum malaria parasites resistant to traditional antimalarial pharmaceuticals. Artemisinin has inhibitory effects on cancer cell growth and anti‐angiogenetic activity, including many drug‐ and radiation‐resistant cancer cell lines. Moloney murine leukemia virus insertion site 1 (BMI‐1) has been shown to regulate proliferation by inhibiting p16ink4a transcription. It is well known that BMI‐1 over‐expression was found in nasopharyngeal carcinoma cell lines and correlated with advanced invasive stage of the tumor progression and poor prognosis. In the present investigation, we analyzed the inhibitory effects of artemisinin on proliferation of nasopharyngeal carcinoma cell lines (CNE‐1 and CNE‐2, well‐differentiated cells, and poorly differentiated cells). We demonstrated that artemisinin induced G1 cell cycle arrest in CNE‐1 and CNE‐2 cells. Artemisinin inhibited BMI‐1 both in protein and transcript levels. BMI‐1 knockdown made the cells more sensitive to artemisinin with an increase in G1 phase, but over‐expression of BMI‐1 partially reversed the artemisinin‐induced G1 cell cycle arrest. Depletion of BMI‐1 was able to intensifying the increment of p16 and the reduction of CDK4 induced by artemisinin. In addition, over‐expression of BMI‐1 was capable of attenuating the increasing p16 and decreasing CDK4 in cells treated with artemisinin. Taking together, the BMI1‐p16/CDK4 axis was involved in the artemisinin‐driven G1 arrest in nasopharyngeal carcinoma cells, and these results indicated that a potential treatment that the combination of artemisinin and BMI‐1 downregulation could enhance the growth inhibitory affects on nasopharyngeal carcinoma cells. J. Cell. Biochem. 112: 1938–1948, 2011. © 2011 Wiley‐Liss, Inc.
Developing and validating the “composite measure of problem behaviors”
Authors: Kingston Jessica , Clarke Sue , Ritchie Timothy , Remington Bob
Published: March 2011

Clinicians frequently encounter problem behaviors such as self‐harm, restrictive eating, binge eating, alcohol misuse, drug misuse, smoking, sexual promiscuity, internet addiction, excessive exercise, and aggression. Although these behaviors commonly co‐occur, no scale exists to measure them concurrently. Based on data from two opportunity samples (N = 691 and N = 53), this study designed and validated a composite measure of the problem behaviors noted above. The Composite Measure of Problem Behaviors, developed using exploratory factor analysis, demonstrated good psychometric properties. Subsequent confirmatory factor analysis, using both the first (N = 691) and a third sample (N = 740), identified a common higher order factor that accounted for covariance between behaviors. Findings thus suggest that despite the formal dissimilarity of behaviors assessed, a common function may explain their covariation. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–16, 2011.
The effect of platinum on the performance of WO3 nanocrystal photocatalysts for the oxidation of Methyl Orange and iso‐propanol
Authors: Joshi Upendra A. , Darwent James R. , Yiu Humphrey H. P. , Rosseinsky Matthew J.
Published: March 2011

BACKGROUND: This research investigated the effect of platinum (Pt) on the reactivity of tungsten oxide (WO3) for the visible light photocatalytic oxidation of dyes.

RESULTS: Nanocrystalline tungsten oxide (WO3) photocatalysts were synthesised by a sol‐gel process and employed for the photocatalytic degradation of Methyl Orange under visible light. For comparison commercial bulk WO3 materials were also studied for the same reaction. These materials were fully characterised using X‐ray diffraction (XRD), UV‐visible diffuse reflection spectroscopy and transmission electron microscopy (TEM). The photocatalytic oxidation of iso‐propanol was used as a model reaction to follow the concomitant reduction of molecular oxygen. No reactions occured in the absence of platinum, which is an essential co‐catalyst for the multi‐electron reduction of oxygen. The platinised WO3 catalysts were stable for multiple oxidation–reduction cycles. The results from the catalytic activity measurements showed that platinised nanocrystalline WO3 is a superior oxidation photocatalyst when compared with bulk WO3. Methyl Orange was completely decolourised in 4 h.

CONCLUSIONS: The enhanced performance of nanocrystalline Pt‐WO3 is attributed to improved charge separation in the nanosized photocatalyst. Platinum is an essential co‐catalyst to reduce oxygen. This photocatalyst could be applied to the treatment of organic pollutants in wastewater, with the advantage of using visible light compared with the widely studied TiO2, which requires UV light. Copyright © 2011 Society of Chemical Industry
Synthesis of new polydentate pyrazolyl‐ethene ligands by interaction of 1H‐pyrazole and 1,1,2,2‐tetrabromoethane in a superbasic medium
Authors: Potapov Andrei S. , Nudnova Evgenia A. , Khlebnikov Andrei I. , Ogorodnikov Vladimir D. , Petrenko Tatiana V.
Published: March 2011

Reaction of pyrazole and 1,1,2,2‐tetrabromoethane in a superbasic medium dimethylsulfoxide‐potassium hydroxide was investigated, and a number of pyrazolyl‐ and bromo‐substituted ethenes, which are the products of concurrent substitution and elimination reactions, were identified. Carrying out the reaction using different reagent mole ratios allowed to selectively isolate Z‐1,2‐bis(pyrazol‐1‐yl)ethene, 1,1,2‐tris(pyrazol‐1‐yl)ethane, and 1,1,2,2‐tetrakis(pyrazol‐1‐yl)ethane. Crystal structure of {Z‐1,2‐bis (pyrazol‐1‐yl)ethene}dichlorozinc was established using X‐ray diffraction method. J. Heterocyclic Chem., (2011).
Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF‐2 and VEGF
Authors: Willems Wouter F. , Larsen Mikko , Giusti Guilherme , Friedrich Patricia F. , Bishop Allen T.
Published: March 2011

Frozen bone allografts are susceptible to nonunion and fracture due to limited revascularization and incomplete bone remodeling. We aim to revascularize bone allografts by combining angiogenesis from implanted arteriovenous (AV) bundles with delivery of fibroblast growth factor (FGF‐2) and/or vascular endothelial growth factor (VEGF) via biodegradable microspheres. Rat femoral diaphyseal allografts were frozen at −80°C, and heterotopically transplanted over a major histocompatibility mismatch. A saphenous AV bundle was inserted into the intramedullary canal. Growth factor was encapsulated into microspheres and inserted into the graft, providing localized and sustained drug release. Forty rats were included in four groups: (I) phosphate‐buffered saline, (II) FGF‐2, (III) VEGF, and (IV) FGF‐2 + VEGF. At 4 weeks, angiogenesis was measured by the hydrogen washout method and microangiography. Bone remodeling was evaluated by quantitative histomorphometry and histology. Bone blood flow was significantly higher in groups III and IV compared to control (p < 0.05). Similarly, bone remodeling was higher in VEGF groups. FGF‐2 had little effect on allograft revascularization. No synergistic effect was observed with use of both cytokines. Delivered in microspheres, VEGF proved to be a potent angiogenic cytokine, increasing cortical bone blood flow and new bone formation in frozen allografts revascularized with an implanted AV bundle. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1431–1436, 2011
Effects of Interleukin‐6 Ablation on Fracture Healing in Mice
Authors: Wallace Aaron , Cooney Timothy E. , Englund Richard , Lubahn John D.
Published: March 2011

This study examined the impact of an interleukin‐6 (IL‐6) knockout on fracture healing in terms of histological and biomechanical responses. Following IACUC approval, tibial fractures were produced in 4‐ to 6‐week‐old IL‐6 knockouts (n = 35) and wild‐type mice (n = 36) and harvested along with contralateral limbs at 2 and 6 weeks postsurgery. Histology quantified stage of healing, lymphocyte infiltration, TRAP+ cells, and osteocalcin deposition. Bend testing established maximum load and stiffness. Based on normality assessments, Mann–Whitney U or independent t‐tests were used for data analysis using a p‐value threshold of 0.05. Stage of healing, lymphocyte infiltration, and osteocalcin deposition were similar for all time points (p ≥ 0.243). TRAP+ cell counts were reduced approximately 10‐fold in the knockout at 2 weeks (p = 0.015) but were similar at 6 weeks (p = 0.689). Force‐to‐failure in knockouts was approximately 40% that of wild‐type mice at 2 weeks (p = 0.040) but similar at 6 weeks (p = 0.735). Knockout bone was about 25% less stiff at 2 weeks but approximately 60% stiffer at 6 weeks (p ≥ 0.110). The absence of IL‐6 during early fracture healing significantly reduced osteoclastogenesis and impaired callus strength. By 6 weeks, most histological and biomechanical parameters were similar to fractures in wild‐type bone. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1437–1442, 2011
Local tissue properties of human osteoarthritic cartilage correlate with magnetic resonance T1rho relaxation times
Authors: Tang Simon Y. , Souza Richard B. , Ries Michael , Hansma Paul K. , Alliston Tamara , Li Xiaojuan
Published: March 2011

The objective of this study is to examine the local relationship between T1ρ relaxation times and the mechanical behavior of human osteoarthritic articular cartilage using high‐resolution magnetic resonance imaging (MRI) and local in situ microindentation. Seven human tibial plateaus were obtained from patients who underwent total knee arthroplasty due to severe osteoarthritis (OA). Three to six sites were selected from each sample for visual classification using the ICRS Outerbridge scale (a total of 36 sites). Samples were imaged by MR, and the local distribution of T1ρ relaxation times were obtained at these selected sites. The elastic and viscoelastic characteristics of the tissue were quantified nondestructively using dynamic microindentation to measure peak dynamic modulus, energy dissipation, and phase angle. Measured Outerbridge scores, MR T1ρ relaxation times, and mechanical properties were highly heterogeneous across each cartilage surface. Site‐specific measures of T1ρ relaxation times correlated significantly with the phase angle (p < 0.001; R = 0.908), a viscoelastic mechanical behavior of the cartilage. The novel combination of high‐resolution MR imaging and microindentation allows the investigation of the local relationship between quantitative MRI and biomechanical properties in highly heterogeneous OA cartilage. These findings suggest that MRI T1ρ can provide a functional assessment of articular cartilage. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1312–1319, 2011
A preliminary study comparing the use of allogenic chondrogenic pre‐differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits
Authors: Dashtdar Havva , Rothan Hussin A. , Tay Terence , Ahmad Raja Elina , Ali Razif , Tay Liang Xin , Chong Pan Pan , Kamarul Tunku
Published: March 2011

Chondrogenic differentiated mesenchymal stem cells (CMSCs) have been shown to produce superior chondrogenic expression markers in vitro. However, the use of these cells in vivo has not been fully explored. In this study, in vivo assessment of cartilage repair potential between allogenic‐derived chondrogenic pre‐differentiated mesenchymal stem cells and undifferentiated MSCs (MSCs) were compared. Bilateral full thickness cartilage defects were created on the medial femoral condyles of 12 rabbits (n = 12). Rabbits were divided into two groups. In one group, the defects in the right knees were repaired using alginate encapsulated MSCs while in the second group, CMSCs were used. The animals were sacrificed and the repaired and control knees were assessed at 3 and 6 months after implantation. Quantitative analysis was performed by measuring the Glycosaminoglycans (GAGs)/total protein content. The mean Brittberg score was higher in the transplanted knees as compared to the untreated knee at 6 months (p < 0.05). Quantitative analysis of GAGs was consistent with these results. Histological and immunohistochemical analysis demonstrated hyaline‐like cartilage regeneration in the transplanted sites. Significant differences between the histological scores based on O'Driscoll histological grading were observed between contralateral knees at both 3 and 6 months (p < 0.05). No significant differences were observed between the Britberg, O'Driscoll scores, and GAGs/total protein content when comparing defect sites treated with MSC and CMSC (p > 0.05). This study demonstrates that the use of either MSC or CMSC produced superior healing when compared to cartilage defects that were untreated. However, both cells produced comparable treatment outcomes. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1336–1342, 2011
Protective role of IL‐1β against post‐arthroplasty Staphylococcus aureus infection
Authors: Bernthal Nicholas M. , Pribaz Jonathan R. , Stavrakis Alexandra I. , Billi Fabrizio , Cho John S. , Ramos Romela Irene , Francis Kevin P. , Iwakura Yoichiro , Miller Lloyd S.
Published: March 2011

MyD88 is an adapter molecule that is used by both IL‐1R and TLR family members to initiate downstream signaling and promote immune responses. Given that IL‐1β is induced after Staphylococcus aureus infections and TLR2 is activated by S. aureus lipopeptides, we hypothesized that IL‐1β and TLR2 contribute to MyD88‐dependent protective immune responses against post‐arthroplasty S. aureus infections. To test this hypothesis, we used a mouse model of a post‐arthroplasty S. aureus infection to compare the bacterial burden, biofilm formation and neutrophil recruitment in IL‐1β‐deficient, TLR2‐deficient and wild‐type (wt) mice. By using in vivo bioluminescence imaging, we found that the bacterial burden in IL‐1β‐deficient mice was 26‐fold higher at 1 day after infection and remained 3‐ to 10‐fold greater than wt mice through day 42. In contrast, the bacterial burden in TLR2‐deficient mice did not differ from wt mice. In addition, implants harvested from IL‐1β‐deficient mice had more biofilm formation and 14‐fold higher adherent bacteria compared with those from wt mice. Finally, IL‐1β‐deficient mice had ∼50% decreased neutrophil recruitment to the infected postoperative joints than wt mice. Taken together, these findings suggest a mechanism by which IL‐1β induces neutrophil recruitment to help control the bacterial burden and the ensuing biofilm formation in a post‐surgical joint. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1621–1626, 2011
Drop‐coating deposition Raman spectroscopy of liposomes
Authors: Kočišová Eva , Procházka Marek
Published: March 2011

Drop‐coating deposition Raman (DCDR) spectroscopy was tested as a potential technique for studying liposomes at very low sample concentrations. We used model liposomes prepared either from 1,2‐distearoyl‐sn‐glycero‐3‐phospocholine or from soybean asolectin, which is composed of various lipids and thus represents a good model of natural membranes. In both cases, deposited samples formed a dried drop with a circular shape with a ring of concentrated liposomes at the edge. Spectral mapping showed that maximum Raman intensity originated from the inner part of the edge ring, while Raman signal gradually decreased in both radial directions. The Raman spectra exhibited excellent reproducibility of spectral characteristics at different locations in the drop, indicating similar conformation and ordering of hydrocarbon lipid chains in the sample. Our results suggest that DCDR spectroscopy can be used for studying lipids in situ, and sensitivity of this technique is at least two orders of magnitude higher than that of conventional Raman microscopy. Copyright © 2011 John Wiley & Sons, Ltd.