bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenolic Glycosides from the Chinese Liverwort Reboulia hemisphaerica
Authors: Wang Li‐Ning , Guo Dong‐Xiao , Wang Shu‐Qi , Wu Chang‐Sheng , Rehman Mujeeb Ur , Lou Hong‐Xiang
Published: June 2011

Four new phenolic glycosides, named rebouosides A–D (1–4, resp.), along with three known ones 2‐(3,4‐dihydroxyphenyl)ethyl 2‐O‐α‐L‐rhamnopyranosyl‐β‐D‐allopyranoside (5), 2‐(3,4‐dihydroxyphenyl)ethyl β‐D‐allopyranoside (6), 2‐(3,4‐dihydroxyphenyl)ethyl β‐D‐glucopyranoside (7), and a nucleoside, inosine (8), were isolated from Chinese liverwort Reboulia hemisphaerica. Their structures were elucidated by acidic hydrolysis and extensive spectroscopic methods, including 2D‐NMR techniques.
The Woodward Research Institute, Robert Burns Woodward (1917–1979) and Chemistry behind the Glass Door
Authors: Craig G. Wayne
Published: June 2011

Certainly a highlight in the career of Nobel Laureate Professor Robert Burns Woodward (1917–1979) was the foundation of the Woodward Research Institute (WRI) at Ciba AG in Basel, Switzerland, in 1963. Woodward's remarkable accomplishments in the development of organic chemistry altered not only our concepts of molecular structure, but also our comprehension of physico‐chemical properties. In his legacy, Woodward devised innovative strategies for natural product syntheses based on brilliant rationale of their properties and an uncanny sense of Nature. The chemistry community benefited not only at Harvard but especially in Basel and Zürich from Woodward's inspiring lectures and the opportunity to learn from the chemistry Meister. This article highlights parts of the chemistry and some personalities that contributed to forefront investigations at the Woodward Research Institute which began at the former Novartis legacy company, Ciba AG, Basel.
Photocycloaddition of 4‐(Alk‐1‐ynyl)‐Substituted Coumarins and Thiocoumarins to 2,3‐Dimethylbuta‐1,3‐diene
Authors: Inhülsen Inga , Chin Karin , Göwert Maren , Margaretha Paul
Published: June 2011

On irradiation (350 nm) in the presence of 2,3‐dimethylbuta‐1,3‐diene (8), 4‐(alk‐1‐ynyl)coumarins 1 afford mixtures of cyclobuta‐ and cycloocta‐annulated products 9 and 10, respectively. In contrast, the corresponding thiocoumarins 2 react with the same diene chemoselectively to give cyclohexa‐annulated products 11.
Synthesis of Poly‐Aib Oligopeptides and Aib‐Containing Peptides via the ‘Azirine/Oxazolone Method’, and Their Crystal Structures
Authors: Dannecker‐Dörig Ingeborg , Linden Anthony , Heimgartner Heinz
Published: June 2011

The protected poly‐Aib oligopeptides Z‐(Aib)n‐N(Me)Ph with n=2–6 were prepared according to the ‘azirine/oxazolone method’, i.e., by coupling amino or peptide acids with 2,2,N‐trimethyl‐N‐phenyl‐2H‐azirin‐3‐amine (1a) as an Aib synthon (Scheme 2). Following the same concept, the segments Z‐(Aib)3‐OH (9) and H‐L‐Pro‐(Aib)3‐N(Me)Ph (20) were synthesized, and their subsequent coupling with N,N′‐dicyclohexylcarbodiimide (DCC)/ZnCl2 led to the protected heptapeptide Z‐(Aib)3‐L‐Pro‐(Aib)3‐N(Me)Ph (21; Scheme 3). The crystal structures of the poly‐Aib oligopeptide amides were established by X‐ray crystallography confirming the 310‐helical conformation of Aib peptides.
Synthesis of Benzimidazoles by Phosphine‐Mediated Reductive Cyclisation of ortho‐Nitro‐anilides
Authors: Duchek Jan , Vasella Andrea
Published: June 2011

Heating ortho‐nitro‐anilides 1–3 and 2‐methyl‐N‐(3‐nitropyridin‐2‐yl)propanamide (5) with 4 equiv. of a phosphine led to the 2‐substituted benzimidazoles 6–8 and to the imidazo[4,5‐b]pyridine 10, respectively, in yields between 45 and 85%. Heating 1 with (EtO)3P effected cyclisation and N‐ethylation, leading to the 1‐ethylbenzimidazole 6b. The slow cyclisation of the N‐pivaloylnitroaniline 2b allowed isolation of the intermediate phosphine imide 11 that slowly transformed into the 1H‐benzimidazole 7b. The structure of 11 was established by crystal‐structure analysis. While the N‐methylated ortho‐nitroacetanilide 3 cyclised to the 1,2‐dimethyl‐1H‐benzimidazole (8), the 2‐methylpropananilide 4 was transformed into 1‐methyl‐3‐(1‐methylethyl)‐2H‐benzimidazol‐2‐one (9).
Investigation and Modeling of winter streamflow timing and magnitude under changing climate conditions for the Catskill Mountain region, New York, USA
Authors: Zion Mark S. , Pradhanang Soni M. , Pierson Donald C. , Anandhi Aavudai , Lounsbury David G. , Matonse Adao H. , Schneiderman Elliot M.
Published: June 2011

Snowfall is an important part of the yearly water balance for the Catskill Mountains in New York State, the location of water supply reservoirs for New York City. Recent studies have shown that the effects of climate change on the hydrology of the Catskills will most likely create (1) a decrease in the proportion of precipitation falling as snow, (2) a shift in the timing of snowmelt that will cause snowmelt‐supplemented streamflow events to occur earlier in the fall and winter, and (3) a decrease in the magnitude of traditionally high April streamflow. The shift in timing of snowmelt‐influenced streamflow events is measured by the winter‐early spring centre of volume (WSCV), defined as the Julian Day on which half the total streamflow volume from January to May occurs. Studies of streamflow, precipitation, and temperature trends in the last 50 years have shown that the WSCV is already earlier by about 5–10 days. This study investigates the use of watershed‐scale snowpack and snowmelt algorithms that are incorporated in two existing watershed water quality models, Generalized Watershed Loading Functions‐Variable Source Area (GWLF‐VSA) and Soil and Water Assessment Tool (SWAT), to capture the potential effects of climate change on the timing and magnitude of streamflow during the late fall, winter, and early spring for the Catskill Mountain region. The GWLF‐VSA model reasonably simulated the recent shifts in the winter streamflow timing, with simulations over the previous 50‐year period yielding shifts in WSCV of 2–15 days. The SWAT model yielded similar results as the GWLF‐VSA simulations. Scenarios of potential climate change 100 years in the future showed a similar shift in direction of timing winter streamflow, but at a larger magnitude than observed to date with WSCV occurring 15–20 days earlier. Copyright © 2011 John Wiley & Sons, Ltd.
TDR pressure cell for monitoring water content retention and bulk electrical conductivity curves in undisturbed soil samples
Authors: Moret‐Fernández D. , Vicente J. , Latorre B. , Lera F. , Castañeda C. , López M. V. , Herrero J.
Published: June 2011

The water retention curve (θ(ψ)), which defines the relationship between soil volumetric water content (θ) and matric potential (ψ), is of paramount importance in characterizing the hydraulic behaviour of soils. However, few methods are so far available for estimating θ(ψ) in undisturbed soil samples. We present a new design of TDR‐pressure cell (TDR‐Cell) for estimating θ(ψ) in undisturbed soil samples. The TDR‐Cell consists of a 50‐mm‐long and 50‐mm internal diameter stainless steel cylinder (which constitutes the outer frame of a coaxial line) attached to a porous ceramic disc and closed at the ends with two aluminium lids. A 49‐mm‐long and 3‐mm‐diameter stainless steel rod, which runs longitudinally through the centre of the cylinder, constitutes the inner rod of a coaxial TDR probe. The TDR‐Cell was used to determine the θ(ψ) curves of a packed sand and seven undisturbed soil samples from three profiles of agricultural soils. These θ(ψ) curves were subsequently compared to those obtained from the corresponding 2‐mm sieved soils using the pressure plate method. Measurements of bulk electrical conductivity, σa, as a function of the water content, σa(θ), of the undisturbed soil samples were also performed. An excellent correlation (R2 = 0·988) was found between the θ values measured by TDR on the different undisturbed soils and the corresponding θ obtained from the soil gravimetric water content. A typical bimodal θ(ψ) function was found for most of the undisturbed soil samples. Comparison between the θ(ψ) curves measured with the TDR‐Cell and those obtained from the 2‐mm sieved soils showed that the pressure plate method overestimates θ at low ψ values. The σa(θ) relationship was well described by a simple power expression (R2 > 0·95), in which the power factor, defined as tortuosity, ranged between 1·18 and 3·75. Copyright © 2011 John Wiley & Sons, Ltd.
Hair dye use and risk of bladder cancer in the New England bladder cancer study
Authors: Koutros Stella , Silverman Debra T. , Baris Dalsu , Zahm Shelia Hoar , Morton Lindsay M. , Colt Joanne S. , Hein David W. , Moore Lee E. , Johnson Alison , Schwenn Molly , Cherala Sai , Schned Alan , Doll Mark A. , Rothman Nathaniel , Karagas Margaret R.
Published: June 2011

Aromatic amine components in hair dyes and polymorphisms in genes that encode enzymes responsible for hair dye metabolism may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by N‐acetyltransferase‐1 (NAT1), NAT2, glutathione S‐transferase Mu‐1 (GSTM1) and glutathione S‐transferase theta‐1 (GSTT1) genotypes in a population‐based case–control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer‐assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration or number of applications of hair dyes and bladder cancer among women or men was apparent, but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer [odds ratio (OR) = 3.3, 95% confidence interval (CI): 1.2–8.9]. Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR = 7.3, 95% CI: 1.6–32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. Although we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene‐environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies.
The mothers and toddlers program, an attachment‐based parenting intervention for substance‐using women: Results at 6‐week follow‐up in a randomized clinical pilot
Authors: Suchman Nancy E. , Decoste Cindy , Mcmahon Thomas J. , Rounsaville Bruce , Mayes Linda
Published: June 2011

Previously, we reported posttreatment findings from a randomized pilot study testing a new attachment‐based parenting intervention for mothers enrolled in substance‐use treatment and caring for children ages birth to 3 years (N.E. Suchman, C. DeCoste, N. Castiglioni, T. McMahon, B. Rounsaville, & L. Mayes, 2010). The Mothers and Toddlers Program (MTP) is a 12‐session, weekly individual parenting therapy that aims to enhance maternal capacity for reflective functioning and soften harsh and distorted mental representations of parenting. In a randomized pilot study, 47 mothers who were enrolled in outpatient substance‐abuse treatment and caring for children between birth and 3 years of age were randomized to the MTP versus the Parent Education Program (PE), a comparison intervention that provided individual case management and developmental guidance. At the end of treatment, mothers in the MTP condition demonstrated better reflective functioning, representation quality, and caregiving behavior than did mothers in the PE condition. In this investigation, we examined whether the benefits of MTP at posttreatment were sustained at the 6‐week follow‐up. Recently, we also identified two components of parental reflective functioning: (a) a self‐focused component representing the parent's capacity to mentalize about strong personal emotions (e.g., anger, guilt, or pain) and their impact on the child and (b) a child‐focused component representing the parent's capacity to mentalize about the child's emotions and their impact on the mother (N. Suchman, C. DeCoste, D. Leigh, & J. Borelli, 2010). In this study, we reexamined posttreatment outcomes using these two related, but distinct, constructs.
Role of SF‐1 and DAX‐1 during differentiation of P19 cells by retinoic acid
Authors: Teets Bryan W. , Soprano Kenneth J. , Soprano Dianne Robert
Published: June 2011

Retinoic acid (RA) is critical for embryonic development and cellular differentiation. Previous work in our laboratory has shown that blocking the RA‐dependent increase in pre‐β cell leukemia transcription factors (PBX) mRNA and protein levels in P19 cells prevents endodermal and neuronal differentiation. Dosage‐sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX‐1) and steroidogenic factor (SF‐1) were found by microarray analysis to be regulated by PBX in P19 cells. To determine the roles of DAX‐1 and SF‐1 during RA‐dependent differentiation, P19 cells that inducibly express either FLAG‐DAX‐1 or FLAG‐SF‐1 were prepared. Unexpectedly, overexpression of DAX‐1 had no effect on the RA‐induced differentiation of P19 cells to either endodermal or neuronal cells. However, SF‐1 overexpression prevented the RA‐dependent loss of OCT‐4, DAX‐1 and the increase in COUP‐TFI, COUP‐TFII, and ETS‐1 mRNA levels during the commitment stages of both endodermal and neuronal differentiation. Surprisingly, continued expression of SF‐1 for 7 days caused the RA‐independent loss of OCT‐4 protein and RA‐dependent loss of SSEA‐1 expression. Despite the loss of well‐characterized pluripotency markers, these cells did not terminally differentiate into either endodermal or neuronal cells. Instead, the cells gained the expression of many steroidogenic enzymes with a pattern consistent with adrenal cells. Finally, we found evidence for a feedback loop in which PBX reduces SF‐1 mRNA levels while continued SF‐1 expression blocks the RA‐dependent increase in PBX levels. Taken together, these data demonstrate that SF‐1 plays a dynamic role during the differentiation of P19 cells and potentially during early embryogenesis. J. Cell. Physiol. 227: 1501–1511, 2012. © 2011 Wiley Periodicals, Inc.
Lactoferricin mediates anabolic and anti‐catabolic effects in the intervertebral disc
Authors: Kim Jae‐Sung , Ellman Michael B. , An Howard S. , Yan Dongyao , van Wijnen Andre J. , Murphy Gillian , Hoskin David W. , Im Hee‐Jeong
Published: June 2011

Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and catabolic growth factors, in addition to pro‐inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix‐degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin‐like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose‐dependent manner. Simultaneously, LfcinB dose‐dependently downregulated catabolic enzymes. LfcinB's anti‐catabolic effects were further demonstrated by a dose‐dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen‐activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX‐9, TIMP‐1, TIMP‐2, TIMP‐3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti‐catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future. J. Cell. Physiol. 227: 1512–1520, 2012. © 2011 Wiley Periodicals, Inc.
Reduction of ribosome biogenesis with activation of the mTOR pathway in denervated atrophic muscle
Authors: Machida Masanao , Takeda Kohei , Yokono Hiroyuki , Ikemune Sachiko , Taniguchi Yuka , Kiyosawa Hidenori , Takemasa Tohru
Published: June 2011

Mammalian target of rapamycin (mTOR) pathway positively regulates the cell growth through ribosome biogenesis in many cell type. In general, myostatin is understood to repress skeletal muscle hypertrophy through inhibition of mTOR pathway and myogenesis. However, these relationships have not been clarified in skeletal muscle undergoing atrophy. Here, we observed a significant decrease of skeletal muscle mass at 2 weeks after denervation. Unexpectedly, however, mTOR pathway and the expression of genes related to myogenesis were markedly increased, and that of myostatin was decreased. However, de novo ribosomal RNA synthesis and the levels of ribosomal RNAs were dramatically decreased in denervated muscle. These results indicate that ribosome biogenesis is strongly controlled by factors other than the mTOR pathway in denervated atrophic muscle. Finally, we assessed rRNA transcription factors expression and observed that TAFIa was the only factor decreased. TAFIa might be a one of the limiting factor for rRNA synthesis in denervated muscle. J. Cell. Physiol. 227: 1569–1576, 2012. © 2011 Wiley Periodicals, Inc.
Human peripheral blood CD34‐positive cells enhance therapeutic regeneration of chronically injured liver in nude rats
Authors: Nakamura Toru , Tsutsumi Victor , Torimura Takuji , Naitou Masako , Iwamoto Hideki , Masuda Hiroshi , Hashimoto Osamu , Koga Hironori , Abe Mitsuhiko , Ii Masaaki , Kawamoto Atsuhiko , Asahara Takayuki , Ueno Takato , Sata Michio
Published: June 2011

We investigated whether transplantation of purified human peripheral blood CD34+ cells could reduce established liver fibrosis and up‐regulate therapeutic regeneration. Human peripheral blood CD34+ cells were isolated from total mononuclear cells of healthy volunteers by magnetic cell sorting. Recipient nude rats were injected intraperitoneally with carbon tetrachloride (CCl4) twice weekly for 3 weeks before single administration of CD34+ cells. CCl4 was then re‐administered twice weekly for 3 more weeks, and the nude rats were sacrificed. Saline (control group), 1 × 105 (low‐dose group), 5 × 105 (middle‐dose group), or 2 × 106 (high‐dose group) CD34+ cells/kg body weight were intrasplenically transplanted after CCl4 treatment for 3 weeks. Reverse transcriptase‐polymerase chain reaction analysis of the freshly isolated CD34+ cells revealed the expression of CD31, keratin19, α‐smooth muscle actin (α‐SMA), and epithelial growth factor, but not other liver related markers. The transplanted cells differentiated into vascular and sinusoidal endothelial cells, and vascular smooth muscle cells. CD34+ cell transplantation reduced liver fibrosis in a dose‐dependent fashion, with decreased collagen type‐I and α‐SMA‐positive cells after 6 weeks of CCl4 treatment by Mallory's Azan and immunohistochemical staining. Gelatin zymography showed that the expression levels of active matrix metalloproteinase‐2 and ‐9 in CD34+ cell transplanted livers were significantly stronger than those in saline‐infused livers. In recipients of high‐doses of CD34+ cells, the number of PCNA‐positive hepatocyte increased 6 weeks after CCl4 treatment compared with saline‐infused livers. We conclude that human peripheral blood CD34+ cell transplantation halts established liver fibrosis and promotes hepatic regeneration in CCl4‐induced chronic liver injury. J. Cell. Physiol. 227: 1538–1552, 2012. © 2011 Wiley Periodicals, Inc.
Interplay between membrane lipid peroxidation, transglutaminase activity, and Cyclooxygenase 2 expression in the tissue adjoining to breast cancer
Authors: Balestrieri Maria Luisa , Dicitore Alessandra , Benevento Raffaella , Di Maio Massimo , Santoriello Antonio , Canonico Silvestro , Giordano Antonio , Stiuso Paola
Published: June 2011

Breast cancer, a leading cause of cancer related deaths worldwide, is one of the most common neoplasms in women. The increased generation of reactive oxygen species (ROS) in breast lesion is critically involved in the mutagenic processes that drive to breast carcinoma initiation and progression. To date, the molecular events occurring in the tissue adjoin the cancer lesion have not been elucidated. Here, we investigated the role of excess ROS generation during human breast carcinogenesis by evaluating oxidative stress biomarkers, tissue transglutaminase (t‐TGase) activity, and expression levels of ubiquitin and cyclooxygenase‐2 (COX‐2) in the normal tissue adjoin to fibroadenoma (nFA), atypical ductal hyperplasia (nADH), and invasive ductal carcinoma (nIDC) from 45 breast cancer patients. We found that lipid peroxidation and nitric oxide production significantly increased in nIDC respect to nFA and nADH (P < 0.005) whereas the 4‐hydroxy‐2‐nonenal (HNE) protein‐adducts increased only in nADH (P < 0.005). The increased lipid damage observed in nIDC correlates with estrogen receptor exposure in IDC (R2 = 0.89). Moreover, nIDC and invasive ductal carcinoma (IDC) showed a 10‐fold higher t‐TGase activity compared to nFA and nADH. Contrary, COX‐2 expression levels significantly decreased nIDC and IDC respect to the nFA and nADH (P < 0.001). The analysis of the free ubiquitin expression revealed equal levels in nADH and nIDC samples whereas high molecular weight‐ubiquitin conjugate increased about fivefold only in nIDC (P < 0.01 vs. nADH). These novel findings reveal an interplay between membrane lipid peroxidation, t‐TGase activity, and COX‐2 expression levels in the tissue adjoining to neoplastic lesion during breast cancer progression. J. Cell. Physiol. 227: 1577–1582, 2012. © 2011 Wiley Periodicals, Inc.
Transactivation of EGFR/PI3K/Akt involved in ATP‐induced inflammatory protein expression and cell motility
Authors: Lin Chih‐Chung , Lin Wei‐Ning , Cheng Shin‐Ei , Tung Wei‐Hsuan , Wang Hui‐Hsin , Yang Chuen‐Mao
Published: June 2011

Phenotype transition of vascular smooth muscle cells (VSMCs) is important in vascular diseases, such as atherosclerosis and restenosis. Once released, ATP may promote activation of VSMCs by stimulating cyclooxygenase‐2 (COX‐2), cytosolic phospholipase A2 (cPLA2) expression and prostaglandin (PG)E2 synthesis via activation of MAPKs and NF‐κB. However, whether alternative signaling pathways participated in regulating COX‐2 and cPLA2 expression associated with cell migration were investigated in rat VSMCs. Western blot analysis, RT‐PCR, promoter assay and PGE2 ELISA were used to determine expression of COX‐2, cPLA2 and PGE2. Specific inhibitors and siRNAs against various protein kinases or transcription factors were used to investigate the related signaling components in inflammatory protein induction by ATPγS. We found that ATPγS‐induced COX‐2 and cPLA2 expression and PGE2 release was attenuated by the pharmacological inhibitors or transfection with siRNA against PKCδ, c‐Src, EGFR, PI3‐K, Akt, p44/p42 MAPK or Elk‐1. Moreover, ATPγS‐stimulated phosphorylation of PKCδ, c‐Src, EGFR, Akt, p42/p44 MAPK and Elk‐1, suggesting the participation of PKCδ/c‐Src/EGFR/PI3‐K/Akt/p42/p44 MAPK cascade in mediating Elk‐1 activities in VSMCs. In addition, migration assay revealed that ATPγS promoted cell mobility through up‐regulation of COX‐2 and cPLA2 expression and PGE2 release, which was attenuated by pretreatment with PGE2 receptor antagonists. Taken together, these data showed that ATPγS up‐regulated the expression of COX‐2 and cPLA2 through transactivation of PKCδ/c‐Src/EGFR/PI3K/Akt/Elk‐1 pathway. Newly synthesized PGE2 acted on its receptors to promote cell motility of ATPγS‐stimulated VSMCs. J. Cell. Physiol. 227: 1628–1638, 2012. © 2011 Wiley Periodicals, Inc.
Angiogenin inhibits nuclear translocation of apoptosis inducing factor in a Bcl‐2‐dependent manner
Authors: Li Shuping , Yu Wenhao , Hu Guo‐Fu
Published: June 2011

Loss‐of‐function mutations in angiogenin (ANG) gene were discovered in amyotrophic lateral sclerosis (ALS) patients and ANG has been shown to prevent neuronal death both in vitro and in vivo. The neuro‐protective activity of ANG was brought about partially by inhibiting stress‐induced apoptosis. ANG attenuates both the extrinsic and the intrinsic apoptotic signals by activating Nf‐κb‐mediated cell survival pathway and Bcl‐2‐mediated anti‐apoptotic pathway. Here we report that ANG inhibits nuclear translocation of apoptosis inducing factor (AIF), an important cell death‐executing molecule known to play a dominant role in neurodegenerative diseases. ANG inhibits serum withdrawal‐induced apoptosis by attenuating a series of Bcl‐2‐dependent events including caspase‐3 activation, poly ADP‐ribose polymerase‐1 (PARP‐1) cleavage, and AIF nuclear translocation. J. Cell. Physiol. 227: 1639–1644, 2012. © 2011 Wiley Periodicals, Inc.
Identification of RUNX3 as a component of the MST/Hpo signaling pathway
Authors: Min Boram , Kim Min‐Kyu , Zhang Joo‐Won , Kim Jiyeon , Chung Kwang‐Chul , Oh Byung‐Chul , Stein Gary S. , Lee Yong‐Hee , van Wijnen Andre J. , Bae Suk‐Chul
Published: June 2011

Recent genetic screens of fly mutants and molecular analysis have revealed that the Hippo (Hpo) pathway controls both cell proliferation and cell death. Deregulation of its human counterpart (the MST pathway) has been implicated in human cancers. However, how this pathway is linked with the known tumor suppressor network remains to be established. RUNX3 functions as a tumor suppressor of gastric cancer, lung cancer, bladder cancer, and colon cancer. Here, we show that RUNX3 is a principal and evolutionarily conserved component of the MST pathway. SAV1/WW45 facilitates the close association between MST2 and RUNX3. MST2, in turn, stimulates the SAV1–RUNX3 interaction. In addition, we show that siRNA‐mediated RUNX3 knockdown abolishes MST/Hpo‐mediated cell death. By establishing that RUNX3 is an endpoint effector of the MST pathway and that RUNX3 is capable of inducing cell death in cooperation with MST and SAV1, we define an evolutionarily conserved novel regulatory mechanism loop for tumor suppression in human cancers. J. Cell. Physiol. 227: 839–849, 2012. © 2011 Wiley Periodicals, Inc.
PML expression in soft tissue sarcoma: Prognostic and predictive value in alkylating agents/antracycline‐based first line therapy
Authors: Vincenzi Bruno , Santini Daniele , Schiavon Gaia , Frezza Anna Maria , Silletta Marianna , Crucitti Pierfilippo , Casali Paolo , Tos Angelo P. Dei , Rossi Sabrina , Rizzo Sergio , Badalamenti Giuseppe , Tomasino Rosa Maria , Russo Antonio , Butrynski James E. , Tonini Giuseppe
Published: June 2011

Soft tissue sarcomas are aggressive tumors representing <1% of all adult neoplasms. Aim of our study was to evaluate promyelocytic leukemia gene expression value as prognostic factor and as a factor predicting response to alkylating agents/antracycline‐based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline‐based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7–41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down‐regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis. J. Cell. Physiol. 227: 1657–1662, 2012. © 2011 Wiley Periodicals, Inc.
The phenotype and functional alterations of macrophages in mice with hyperglycemia for long term
Authors: Sun Chenming , Sun Lina , Ma Haixia , Peng Jianxia , Zhen Yu , Duan Kaizhong , Liu Guangwei , Ding Wenjun , Zhao Yong
Published: June 2011

Abnormal immunity and its related complications are the major causes of mortality and morbidity in diabetes patients. Macrophages, as one of the important innate cells, play pivotal roles in controlling immune homeostasis, immunity, and tolerance. The effects of hyperglycemia on the function of macrophages in hosts remain to be determined. Here we used mice with streptozotocin (STZ)‐induced diabetes for long term to study the changes of macrophages. We found that F4/80+ peritoneal exudate macrophages (PEMs) from mice with diabetes for 4 months displayed significantly reduced CD86 and CD54 expression and tumor necrosis factor (TNF)‐α and IL‐6 production but enhanced nitric oxide (NO) secretion compared with control mice when treated with interferon (IFN)‐γ and lipopolysaccharide (LPS), while the activity of arginase in PEMs from diabetic mice was significantly higher than control mice when stimulating with IL‐4. These dysfunctions of macrophages could be efficiently reversed by insulin treatment. Importantly, in vitro bone marrow‐derived macrophages showed similar functional changes, indicating the epigenetic alteration of macrophage precursors in these mice. In an in vitro culture system, high glucose and insulin significantly altered TNF‐α, IL‐6, and NO production and arginase activity of macrophages, which was reversed by the treatment with AKT and ERK inhibitors. Therefore, hyperglycemia and insulin deficiency can modify macrophage function through AKT‐mTOR and ERK pathways and through epigenetic effects on macrophage precursors. To further identify different components of diabetes on the dysfunction of macrophages is important for efficient prevention of diabetic complications. J. Cell. Physiol. 227: 1670–1679, 2012. © 2011 Wiley Periodicals, Inc.
Human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by AMP‐activated protein kinase
Authors: Kim Eung‐Kyun , Lim Seyoung , Park Ji‐Man , Seo Jeong Kon , Kim Jae Ho , Kim Kyong Tai , Ryu Sung Ho , Suh Pann‐Ghill
Published: June 2011

AMP‐activated protein kinase (AMPK) is an energy‐sensing kinase that has recently been shown to regulate the differentiation of preadipocytes and osteoblasts. However, the role of AMPK in stem cell differentiation is largely unknown. Using in vitro culture models, the present study demonstrates that AMPK is a critical regulatory factor for osteogenic differentiation. We observed that expression and phosphorylation of AMPK were increased during osteogenesis in human adipose tissue‐derived mesenchymal stem cells (hAMSC). To elucidate the role of AMPK in osteogenic differentiation, we investigated the effect of AMPK inhibition or knockdown on mineralization of hAMSC. Compound C, an AMPK inhibitor, reduced mineralized matrix deposition and suppressed the expression of osteoblast‐specific genes, including alkaline phosphatase (ALP), runt‐related transcription factor 2 (RUNX2), and osteocalcin (OCN). Knockdown of AMPK by shRNA‐lentivirus infection also reduced osteogenesis. In addition, inhibition or knockdown of AMPK during osteogenesis inhibited ERK phosphorylation, which is required for osteogenesis. Interestingly, inhibition of AMPK induced adipogenic differentiation of hAMSC, even in osteogenic induction medium (OIM). These results provide a potential mechanism involving AMPK activation in osteogenic differentiation of hAMSC and suggest that commitment of hAMSC to osteogenic or adipogenic lineage is governed by activation or inhibition of AMPK, respectively. J. Cell. Physiol. 227: 1680–1687, 2012. © 2011 Wiley Periodicals, Inc.
A viable technology to generate third‐generation biofuel
Authors: Singh Anoop , Olsen Stig Irving , Nigam Poonam Singh
Published: June 2011

First generation biofuels are widely available because the production technologies are well developed. However, growth of the raw materials conflicts with food security, so that first‐ generation biofuels are not so promising. The second generation of biofuels will not compete directly with food but requires several energy intensive processes to produce them, and also increases land‐use change, which reduces its environmental and economic feasibility. The production of third‐generation biofuels avoids the issues met with first‐ and second‐ generation biofuels, namely food–fuel competition, land‐use change, etc., and is thus considered a viable alternative energy resource. On all dimensions of sustainability (environmental, social and economical), a life cycle assessment approach is most relevant to avoid issues in problem shifting. The utilization of organic waste and carbon dioxide in flue gases for the production of biomass further increases the sustainability of third generation biofuels, as it minimizes greenhouse gas emissions and disposal problems. Copyright © 2011 Society of Chemical Industry
Effect of pre‐treatments based on UV photocatalysis and photo‐oxidation on toluene biofiltration performance
Authors: Palau Jordi , Penya‐Roja Josep M. , Gabaldón Carmen , Álvarez‐Hornos Francisco Javier , Martínez‐Soria Vicente
Published: June 2011

BACKGROUND: The integration of UV photocatalysis and biofiltration seems to be a promising combination of technologies for the removal of hydrophobic and poorly biodegradable air pollutants. The influence of pre‐treatments based on UV254 nm photocatalysis and photo‐oxidation on the biofiltration of toluene as a target compound was evaluated in a controlled long‐term experimental study using different system configurations: a standalone biofilter, a combined UV photocatalytic reactor‐biofilter, and a combined UV photo‐oxidation reactor (without catalyst)‐biofilter.

RESULTS: Under the operational conditions used (residence time of 2.7 s and toluene concentrations 600–1200 mg C m−3), relatively low removal efficiencies (6–3%) were reached in the photocatalytic reactor and no degradation of toluene was found when the photo‐oxidation reactor was operated without catalyst. A noticeable improvement in the performance of the biofilter combined with a photocatalytic reactor was observed, and the elimination capacity of the biological process increased by more than 12 g C h−1 m−3 at the inlet loads studied of 50–100 g C h−1 m−3. No positive effect on toluene removal was observed for the combination of UV photoreactor and biofilter.

CONCLUSIONS: Biofilter pre‐treatment based on UV254 nm photocatalysis showed promising results for the removal of hydrophobic and recalcitrant air pollutants, providing synergistic improvement in the removal of toluene. Copyright © 2011 Society of Chemical Industry
MRT letter: Nanoscopy of protein colocalization in living cells by STED and GSDIM
Authors: Lalkens Birka , Testa Ilaria , Willig Katrin I. , Hell Stefan W.
Published: June 2011

We report the use of superresolution fluorescence microscopy for studying the nanoscale distribution of protein colocalization in living mammalian cells. Nanoscale imaging is attained both by a targeted and a stochastic fluorescence on‐off switching superresolution method, namely by stimulated emission depletion (STED) and ground state depletion microscopy followed by individual molecular return (GSDIM), respectively. Analysis of protein colocalization is performed by bimolecular fluorescence complementation (BiFC). Specifically, a nonfluorescent fragment of the yellow fluorescent protein Citrine is fused to tubulin while a counterpart nonfluorescent fragment is fused to the microtubulin‐associated protein MAP2 such that fluorescence is reconstituted on contact of the fragment‐carrying proteins. Images with resolution down to 65 nm prove a powerful new way for studying protein colocalization in living cells at the nanoscale. Microsc. Res. Tech., 2012. © 2011 Wiley Periodicals, Inc.
Transmission electron microscopy as a tool to image bioinorganic nanohybrids: The case of phage‐gold nanocomposites
Authors: Cao Binrui , Xu Hong , Mao Chuanbin
Published: June 2011

In recent years, bioinorganic nanohybrids composed of biological macromolecules and functional inorganic nanomaterials have revealed many unique properties that show promise for the future. Transmission electron microscopy (TEM) is a popular and relatively simple tool that can offer a direct visualization of the nanomaterials with high resolutions. When TEM is applied to visualize bioinorganic nanohybrids, a treatment of negative staining is necessary due to the presence of biological molecules in the nanohybrids except for those with densely packed inorganic materials. However, the conventional negative‐staining procedure for regular biological samples cannot be directly applied to such bioinorganic nanohybrids. To image a specific bioinorganic nanohybrid, negative‐staining factors such as negative stain type, working pH, staining time, and drying method, should be identified. Currently, no detailed studies have been done to investigate how to adjust negative‐staining factors based on specific bioinorganic nanohybrids. In this study, bacteriophage‐gold nanoparticle hybrids were chosen as a model to systematically study the effects of each factor on the negative staining of the nanohybrids. The best staining conditions for gold nanoparticle‐phage nanohybrids were obtained and the effects of each factor on the negative staining of general nanohybrids were discussed. This work indicates that with proper staining it is possible to use TEM to visualize directly both biological and inorganic components without introducing any artifact. Microsc. Res. Tech. 2011. © 2011 Wiley‐Liss, Inc.
Degranulation of mast cells due to compound 48/80 induces concentration‐dependent intestinal contraction in rainbow trout (Oncorhynchus mykiss Walbaum) ex vivo
Authors: Manera M. , Giammarino A. , Borreca C. , Giari L. , Dezfuli B.S.
Published: June 2011

Rainbow trout (Oncorhynchus mykiss) intestinal strips (n = 10) were mounted in an isolated organ bath and the effect of incremental doses of compound 48/80 was recorded. Compound 48/80 induced concentration‐related contraction in all the examined strips following a sigmoidal dose–response curve fit. Values for maximal contraction (Emax, g cm−2), negative logarithm of the EC50 (pD2), and hill slope were, respectively (mean±standard error), 12.88 ± 0.51, 1.88 ± 0.05, 1.49 ± 0.27. The histological modification induced on mast cells (MCs) due to compound 48/80 was characterized by mean of gray‐levels and texture analysis. Significant differences were observed between gray‐levels values (Linear mixed model, P<0.01), contrast, and entropy (Linear mixed model, P<0.05) of MCs from compound 48/80‐treated strips compared with MCs from untreated strips. Moreover, maximal intestinal contraction (due to compound 48/80) correlates positively and significantly (Pearson and Spearman correlations, P<0.05) with degranulation intensity determined by means of gray‐levels analysis. Four antisera were tested on intestinal sections and no MCs positive to serotonin, substance P, met‐enkephalin, and bombesin were found. This study demonstrates that compound 48/80 induces the degranulation of trout intestinal MCs ex vivo, and that the aforementioned degranulation promotes a concentration‐dependent intestinal contraction. J. Exp. Zool. 315:447–457, 2011. © 2011 Wiley‐Liss, Inc.
The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster as a therapeutic suicide gene of breast cancer cells
Authors: Ma Shuai , Zhao Lei , Zhu Zhi , Liu Qun , Xu Huimian , Johansson Magnus , Karlsson Anna , Zheng Xinyu
Published: June 2011

Background

The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm‐dNK) was investigated for its broader substrate specificity and higher catalytic rate as a suicide gene in a combined gene/chemotherapy of cancer.

Methods

To evaluate the effects of nucleoside analog phosphorylation by Dm‐dNK in vitro and in vivo, we generated a replication‐deficient retroviral vector expressing Dm‐dNK to transduce human breast cancer cells MCF7 (ER+) and MDA‐MB‐231 (ER–). We further determined the enzymatic activity and the sensitivity of the nontransduced and Dm‐dNK‐transduced 231/dNK and MCF7/dNK cells to the pyrimidine nucleoside analogs araC and araT.

Results

The data obtained show that Dm‐dNK is enzymatically active and its overexpression in the nuclei of breast cancer cells results in an increased sensitivity to the nucleoside analogs araC and araT in vitro. Furthermore, subcutaneously transplanted 231/dNK cells were significantly inhibited after araC treatment, whereas nontransduced cancer cells continued to grow and develop in vivo.

Conclusions

These results suggest that the Dm‐dNK/nucleoside analog system could be a novel therapeutic strategy for treating breast cancer and improving anti‐tumor efficacy, as well as for optimizing approaches for suicide gene therapy. Copyright © 2011 John Wiley & Sons, Ltd.
A single direct injection into the left ventricular wall of an adeno‐associated virus 9 (AAV9) vector expressing extracellular superoxide dismutase from the cardiac troponin‐T promoter protects mice against myocardial infarction
Authors: Prasad Konkal‐Matt R. , Smith Robert S. , Xu Yaqin , French Brent A
Published: June 2011

Background

Localized administration of a highly efficient gene delivery system in combination with a cardiac‐selective promoter may provide a favorable biosafety profile in clinical applications such as coronary artery bypass graft surgery, where regions of myocardium can be readily injected to protect them against the potential threat of future ischemic events.

Methods

Adeno‐associated virus (AAV) vectors expressing luciferase or enhanced green fluorescent protein (eGFP) packaged into AAV serotypes 1, 2, 6, 8 and 9 were injected into the left ventricular (LV) wall of adult mice to determine the time course, magnitude and distribution of gene expression. An AAV9 vector expressing extracellular superoxide dismutase (EcSOD) from the cardiac troponin T (cTnT) promoter was then directly injected into the LV wall of adult mice. Myocardial infarction was induced 4 weeks after injection and infarct size was determined by triphenyltetrazolium chloride and phthalo blue staining.

Results

Serotypes AAV 9, 8, 1 and 6 provided early onset of gene expression in the heart with minimal extra‐cardiac gene expression. AAV9 provided the highest magnitude of gene expression. Immunostaining for eGFP showed expression spanning the anterior to posterior walls from the mid ventricle to the apex. A single direct injection of the AAV9 vector bearing EcSOD (n = 5) decreased the mean infarct size by 50% compared to the eGFP control group (n = 8) (44 ± 7% versus 22 ± 5%; p = 0.04).

Conclusions

AAV serotype 9 is highly efficient for cardiac gene delivery, as evidenced by early onset and high‐level gene expression. AAV9‐mediated, cardiac selective overexpression of EcSOD from the cTnT promoter significantly reduced infarct size in mice. Copyright © 2011 John Wiley & Sons, Ltd.
Effect of poly(ADP‐ribose) polymerase 1 on integration of the adeno‐associated viral vector genome
Authors: Romanova Liudmila G. , Zacharias Jeana , Cannon Mark L. , Philpott Nicola J.
Published: June 2011

Background

Adeno‐associated virus type 2 (AAV) has the ability to target integration of its DNA into a specific locus of the human genome. Site‐specific AAV integration is mediated by viral Rep proteins, although the role of cellular factors involved in this process is largely unknown. Recent studies provide evidence showing that cellular DNA repair proteins are involved in targeted integration of AAV, although their specific roles are not well defined.

Methods

In the present study, we investigated the interaction between Rep and proteins of the back‐up nonhomologous end‐joining pathway (B‐NHEJ). We then analyzed the effect of one of these proteins, poly(ADP‐ribose) polymerase 1 (PARP1) on AAV integration.

Results

We show that AAV Rep interacts with B‐NHEJ members DNA ligase III and PARP1 but does not associate with the scaffolding factor XRCC1. Moreover, PARP1 and Rep bind directly and not via DNA–protein interactions. We also found that Rep increases the enzymatic activity of PARP1 potentially through the endonuclease activity of Rep. Finally, we demonstrate that both chemical inhibition of PARP1 and PARP1 depletion using small hairpin RNA enhance integration of the AAV genome in HeLa cells.

Conclusions

The findings of the present study indicate that manipulation of PARP1 activity could be used as a tool for developing new, effective AAV‐based therapies for the treatment of genetic diseases and cancer. Copyright © 2011 John Wiley & Sons, Ltd.
Decreased expression of surfactant protein D mRNA in human lungs in fatal cases of H5N1 avian influenza
Authors: Kongchanagul Alita , Suptawiwat Ornpreya , Boonarkart Chompunuch , Kitphati Rungrueng , Puthavathana Pilaipan , Uiprasertkul Mongkol , Auewarakul Prasert
Published: June 2011

Microarray analysis of gene expression profile of lungs from two fatal H5N1 influenza cases identified 3,435 genes with higher than twofold changes in mRNA levels as compared to those of normal lung. One thousand nineteen genes and 2,416 genes were up‐regulated and down‐regulated commonly, respectively. Gene ontology analysis identified several ontology terms with significant association with these genes, most of which are related to cellular metabolism and regulation of cellular process including apoptosis and chemotaxis. Pulmonary surfactant protein D (SP‐D) was found to be down‐regulated. Quantitative RT‐PCR confirmed the levels of SP‐D mRNA in the lungs infected with H5N1 to be lower than those of normal lungs and lungs from patients with acute respiratory distress syndrome. SP‐D plays multiple roles in respiratory innate defense against various pathogens, regulation of inflammatory responses, and maintenance of alveolar integrity. Reduction of SP‐D in H5N1 influenza may play important roles in the pathogenesis of the disease. J. Med. Virol. 83:1410–1417, 2011. © 2011 Wiley‐Liss, Inc.
Positive Epstein–Barr virus and cytomegalovirus IgM assays in primary HIV infection
Authors: Post Jeffrey J. , Chan Mun Khin , Whybin L. Ross , Shi Qin , Rawlinson William D. , Cunningham Philip , Robertson Peter W.
Published: June 2011

We report three cases with misleading cytomegalovirus (CMV) or Epstein–Barr virus (EBV) immunoglobulin M (IgM) results during primary human immunodeficiency virus (HIV) infection. We determined the rate of positive anti‐CMV IgM assays or anti‐EBV capsid antigen IgM assays in sera from a group of well‐characterized subjects with primary HIV infection as 2.9% (1/35; 95%CI: 0.15–16.6%) for each infection. The rate of positive anti‐EBV capsid antigen IgM assays in subjects with positive hepatitis A virus IgM assays was 30% (6/20; 95%CI: 14.6–51.9%). Clinicians need to consider the limitations of IgM assays for diagnosis of herpesvirus infections, and consider testing for other infections with overlapping clinical manifestations. J. Med. Virol. 83:1406–1409, 2011. © 2011 Wiley‐Liss, Inc.