bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the default‐mode component in spatial IC analyses of patients with disorders of consciousness
Authors: Soddu Andrea , Vanhaudenhuyse Audrey , Bahri Mohamed Ali , Bruno Marie‐Aurelie , Boly Mélanie , Demertzi Athena , Tshibanda Jean‐Flory , Phillips Christophe , Stanziano Mario , Ovadia‐Caro Smadar , Nir Yuval , Maquet Pierre , Papa Michele , Malach Rafael , Laureys Steven , Noirhomme Quentin
Published: April 2011

Objectives:Recent fMRI studies have shown that it is possible to reliably identify the default‐mode network (DMN) in the absence of any task, by resting‐state connectivity analyses in healthy volunteers. We here aimed to identify the DMN in the challenging patient population of disorders of consciousness encountered following coma. Experimental design: A spatial independent component analysis‐based methodology permitted DMN assessment, decomposing connectivity in all its different sources either neuronal or artifactual. Three different selection criteria were introduced assessing anticorrelation‐corrected connectivity with or without an automatic masking procedure and calculating connectivity scores encompassing both spatial and temporal properties. These three methods were validated on 10 healthy controls and applied to an independent group of 8 healthy controls and 11 severely brain‐damaged patients [locked‐in syndrome (n = 2), minimally conscious (n = 1), and vegetative state (n = 8)]. Principal observations: All vegetative patients showed fewer connections in the default‐mode areas, when compared with controls, contrary to locked‐in patients who showed near‐normal connectivity. In the minimally conscious‐state patient, only the two selection criteria considering both spatial and temporal properties were able to identify an intact right lateralized BOLD connectivity pattern, and metabolic PET data suggested its neuronal origin. Conclusions: When assessing resting‐state connectivity in patients with disorders of consciousness, it is important to use a methodology excluding non‐neuronal contributions caused by head motion, respiration, and heart rate artifacts encountered in all studied patients. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Hh‐Gli signaling pathway activity in oral and oropharyngeal squamous cell carcinoma
Authors: Leovic Dinko , Sabol Maja , Ozretic Petar , Musani Vesna , Car Diana , Marjanovic Ksenija , Zubcic Vedran , Sabol Ivan , Sikora Miroslav , Grce Magdalena , Glavas‐Obrovac Ljubica , Levanat Sonja
Published: April 2011

Background

The aim of this study was to examine the role of Hh‐Gli signaling in oral and oropharyngeal squamous cell carcinoma (SCC). The role of this signaling pathway in SCC formation has not yet been elucidated.

Methods

Sixty‐four tissue and blood samples were collected from 60 patients with SCC, all tobacco and alcohol users. An additional six buccal mucosa tissue samples were collected from nonsmokers and nondrinkers as control tissue.

Results

Hedgehog‐Gli pathway components were associated with clinical and pathologic features. Broders' grade and N stage were associated with higher Ptch1 and lower Gli1 expression. Tumor stage was negatively associated with Smo expression, and tumor size was positively associated with p16 expression. Ptch1 and Shh were frequently detected in the surrounding stroma. Ptch1 was found to be correlated with p16 expression, as well as with survivin expression.

Conclusions

The signaling pathway is activated in SCC and inducible in vitro by Shh protein. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C
Authors: Trépo Eric , Pradat Pierre , Potthoff Andrej , Momozawa Yukihide , Quertinmont Eric , Gustot Thierry , Lemmers Arnaud , Berthillon Pascale , Amininejad Leila , Chevallier Michéle , Schlué Jerome , Kreipe Hans , Devière Jacques , Manns Michael , Trépo Christian , Sninsky John , Wedemeyer Heiner , Franchimont Denis , Moreno Christophe
Published: April 2011

Abstract:

Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and fibrosis progression remains highly unpredictable. A recent genome-wide association study identified a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis in nonalcoholic fatty liver disease. The aim of this study was to assess the impact of this polymorphism on histological liver damage and response to antiviral therapy in CHC. We recruited 537 Caucasian CHC patients from three European centers (Brussels, Belgium [n = 229]; Hannover, Germany [n = 171]; Lyon, France [n = 137]); these patients were centrally genotyped for the PNPLA3 (rs738409 C>G) polymorphism. We studied the influence of rs738409 and other variants in the PNPLA3 region on steatosis and fibrosis assessed both in a cross-sectional and longitudinal manner. Seven other variants previously associated with fibrosis progression were included. Finally, we explored the impact of rs738409 on response to standard antiviral therapy using the interferon lambda 3 (IL28B) [rs12979860 C>T] variant both as a comparator and as a positive control. After adjustment for age, sex, body mass index, alcohol consumption, and diabetes, rs738409 mutant G allele homozygote carriers remained at higher risk for steatosis (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.08–6.03, P = 0.034), fibrosis (OR 3.13, 95% CI 1.50–6.51, P = 0.002), and fibrosis progression (OR 2.64, 95% CI 1.22–5.67, P = 0.013). Conversely, rs738409 was not independently associated with treatment failure (OR 1.07, 95% CI 0.46–2.49, P = 0.875) and did not influence clinical or biological variables. Conclusion: The PNPLA3 (rs738409 C>G) polymorphism favors steatosis and fibrosis progression in CHC. This polymorphism may represent a valuable genetic predictor and a potential therapeutic target in CHC liver damage. (HEPATOLOGY 2011;)
Risk factors for cholangiocarcinoma
Authors: Tyson Gia L. , El-Serag Hashem B.
Published: April 2011

Abstract:

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy after hepatocellular cancer. CC accounts for approximately 10%-25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of CC. There are several established risk factors for CC, including parasitic infections, primary sclerosing cholangitis, biliary-duct cysts, hepatolithiasis, and toxins. Other less-established potential risk factors include inflammatory bowel disease, hepatitis C virus, hepatitis B virus, cirrhosis, diabetes, obesity, alcohol drinking, tobacco smoking, and host genetic polymorphisms. In studies where the distinction between intra- and extrahepatic CC was used, some potential risk factors seem to have a differential effect on CC, depending on the site. Therefore, the consistent use of a more refined classification would allow a better understanding of risk factors for CC. (HEPATOLOGY 2011;)
Apoptosis signal-regulating kinase 1 inhibits hepatocarcinogenesis by controlling the tumor-suppressing function of stress-activated mitogen-activated protein kinase
Authors: Nakagawa Hayato , Hirata Yoshihiro , Takeda Kohsuke , Hayakawa Yoku , Sato Takehiro , Kinoshita Hiroto , Sakamoto Kei , Nakata Wachiko , Hikiba Yohko , Omata Masao , Yoshida Haruhiko , Koike Kazuhiko , Ichijo Hidenori , Maeda Shin
Published: April 2011

Abstract:

The stress-activated mitogen-activated protein kinases (MAPKs), c-Jun NH2-terminal kinase (JNK), and p38 have been implicated in hepatocarcinogenesis. Although the many interrelated functions of JNK and p38 are precisely regulated by upstream signaling molecules, little is known about upstream regulators. We investigated the role of apoptosis signal-regulating kinase 1 (ASK1), a major player in the regulation of JNK and p38 activities, in hepatocarcinogenesis using a mouse hepatocellular carcinoma (HCC) model. ASK1-deficient (ASK1−/−) and wildtype (WT) mice were treated with diethylnitrosamine on postnatal day 14. Strikingly, after 7 months, approximately three times as many tumors developed in ASK1−/− mice as in WT mice. Although JNK and p38 activation were attenuated in ASK1−/− HCCs relative to WT HCCs, cell proliferation was comparable in HCCs from both types of mice. On the other hand, both cancer cell apoptosis and hyperphosphorylation of BimEL, a proapoptotic Bcl-2 family member, were suppressed in the ASK1−/− HCCs. ASK1−/− mice showed remarkable resistance to Fas-induced hepatocyte apoptosis in vivo, probably because of attenuated JNK-mediated BimEL phosphorylation and mitochondrial apoptotic pathway activation. The reintroduction of ASK1 to ASK1−/− mouse liver using an adenoviral vector restored Fas-induced hepatocyte death and phosphorylation of JNK and BimEL. Similar findings were obtained in tumor necrosis factor alpha-induced hepatocyte apoptosis. Furthermore, ASK1 was involved in DNA damage-induced p21 up-regulation through a p38 pathway. Conclusion: ASK1 is involved in death receptor-mediated apoptosis and DNA-damage response by way of stress-activated MAPK in the liver, and thus acts as a tumor suppressor in hepatocarcinogenesis. This study provides new insight into the regulation of stress- activated MAPK signaling in hepatocarcinogenesis. (HEPATOLOGY 2011;)
Racial differences in hepatitis C treatment eligibility
Authors: Melia Michael T. , Muir Andrew J. , McCone Jonathan , Shiffman Mitchell L. , King John W. , Herrine Steven K. , Galler Greg W. , Bloomer Joseph R. , Nunes Frederick A. , Brown Kimberly A. , Mullen Kevin D. , Ravendhran Natarajan , Ghalib Reem H. , Boparai Navdeep , Jiang Ruiyun , Noviello Stephanie , Brass Clifford A. , Albrecht Janice K. , McHutchison John G. , Sulkowski Mark S.
Published: April 2011

Abstract:

Black Americans are disproportionally infected with hepatitis C virus (HCV) and are less likely than whites to respond to treatment with peginterferon (PEG-IFN) plus ribavirin (RBV). The impact of race on HCV treatment eligibility is unknown. We therefore performed a retrospective analysis of a phase 3B multicenter clinical trial conducted at 118 United States community and academic medical centers to evaluate the rates of and reasons for HCV treatment ineligibility according to self-reported race. In all, 4,469 patients were screened, of whom 1,038 (23.2%) were treatment ineligible. Although blacks represented 19% of treated patients, they were more likely not to be treated due to ineligibility and/or failure to complete required evaluations (40.2%) than were nonblack patients (28.5%; P < 0.001). After the exclusion of persons not treated due to undetectable HCV RNA or nongenotype 1 infection, blacks were 65% less likely than nonblacks to be eligible for treatment (28.1% > 17.0%; relative risk, 1.65; 95% confidence interval, 1.46–1.87; P < 0.001). Blacks were more likely to be ineligible due to neutropenia (14% versus 3%, P < 0.001), anemia (7% versus 4%, P = 0.02), elevated glucose (8% versus 3%, P < 0.001), and elevated creatinine (5% versus 1%, P < 0.001). Conclusion: Largely due to a higher prevalence of neutropenia and uncontrolled medical conditions, blacks were significantly less likely to be eligible for HCV treatment. Increased access to treatment may be facilitated by less conservative neutrophil requirements and more effective care for chronic diseases, namely, diabetes and renal insufficiency. (HEPATOLOGY 2011;)
New Anthraquinone and Iridoid Glycosides from the Stems of Hedyotis hedyotidea
Authors: Hu Xiao‐Ping , Zhang Shu‐Wei , Liu Shan‐Shan , Xuan Li‐Jiang
Published: April 2011

Five new anthraquinone glycosides, hedanthrosides A–E (1–5, resp.) and two new iridoid glycosides, hediridosides A and B (6 and 7, resp.), along with two known anthraquinones and four known iridoids, were isolated from the stems of Hedyotis hedyotidea (DC.) Merr. The structures of the new compounds were elucidated on the basis of 1D‐ and 2D‐NMR, and HR‐MS analysis and chemical methods.
Two Glycosides and Other Constituents from Anemone tomentosa Roots
Authors: Hu Hao‐Bin , Zheng Xu‐Dong , Zhu Ji‐Hua , Zhang Xiao‐Wei
Published: April 2011

Two new natural products, i.e., 1‐O,2‐O‐[(1S,2S)‐1‐(3‐acetyl‐2,4,6‐trihydroxyphenyl)‐3‐hydroxypropane‐1,3‐diyl]‐β‐D‐glucopyranose (=tomentoside I; 1) and (3β)‐3‐(acetyloxy)ferruginol 12‐[6‐O‐(4‐hydroxy‐3,5‐dimethoxybenzoyl)‐β‐D‐glucopyranoside] (=tomentoside II; 2), were isolated from the EtOH extract of the root of Anemone tomentosa, together with five known compounds. Their structures were characterized by means of spectroscopic methods, especially by 1H‐, 13C‐, and 2D‐NMR and HR‐MS, as well as by chemical methods and comparison with literature data.
Silica Nanoparticles as a Highly Efficient Catalyst for the One‐Pot Synthesis of 2‐Hydroxyacetamide Derivatives from Isocyanides and Electron‐Poor Aromatic Aldehydes
Authors: Ramazani Ali , Mahyari Amir , Lashgari Hamed , Ślepokura Katarzyna , Lis Tadeusz
Published: April 2011

Reaction of an isocyanide with an electron‐poor aromatic aldehyde in the presence of silica nanoparticles (silica NP; ca. 42 nm) proceeds smoothly at room temperature to afford 2‐hydroxyacetamide derivatives in high yields (Scheme 1 and Table 1).
Three New Triterpenoid Saponins from Ardisia crenata
Authors: Liu Dai‐Lin , Wang Nai‐Li , Zhang Xue , Yao Xin‐Sheng
Published: April 2011

Three new triterpenoid saponins, ardisicrenoside I (1), ardisicrenoside J (2), and ardisicrenoside M (3), along with eight known compounds, were isolated from the roots of Ardisia crenata Sims. Their structures were elucidated as 16α‐hydroxy‐30,30‐dimethoxy‐3β‐O‐{β‐D‐xylopyranosyl‐(1→2)‐β‐D‐glucopyranosyl‐(1→4)‐[β‐D‐glucopyranosyl‐(1→2)]‐α‐L‐arabinopyranosyl}‐13β,28‐epoxyoleanane (1), 16α‐hydroxy‐30,30‐dimethoxy‐3β‐O‐{α‐L‐rhamnopyranosyl‐(1→2)‐β‐D‐glucopyranosyl‐(1→4)‐[β‐D‐glucopyranosyl‐(1→2)]‐α‐L‐arabinopyranosyl}‐13β,28‐epoxyoleanane (2), 30,30‐dimethoxy‐16‐oxo‐3β‐O‐{β‐D‐xylopyranosyl‐(1→2)‐β‐D‐glucopyranosyl‐(1→4)‐[β‐D‐glucopyranosyl‐(1→2)]‐α‐L‐arabinopyranosyl}‐13β,28‐epoxyoleanane (3), ardisiacrispin A (4), ardisiacrispin B (5), ardisicrenoside B (6), ardisicrenoside A (7), ardisicrenoside H (8), ardisicrenoside G (9), cyclamiretin A‐3β‐O‐β‐D‐xylopyranosyl‐(1→2)‐β‐D‐glucopyranosyl‐(1→4)‐α‐L‐arabinopyranoside (10), and cyclamiretin A‐3β‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐β‐D‐glucopyranosyl‐(1→4)‐α‐L‐arabinopyranoside (11) by means of chemical and spectral analysis, and their cytotoxicities were evaluated in vitro.
Influence of Variation of a Side Chain on the Folding Equilibrium of a β‐Peptide
Authors: Lin Zhixiong , Hodel Florian H. , van Gunsteren Wilfred F.
Published: April 2011

The ability to design well‐folding β‐peptides with a specific biological activity requires detailed insight into the relationship between the β‐amino acid sequence and the three‐dimensional structure of the peptide. Here, we present a molecular‐dynamics (MD) study of the influence of a variation of a side chain on the folding equilibrium of a β‐heptapeptide that folds into a 314‐helical structure. The side chain of the 5th residue, a valine, was changed into five differently branched side chains of different lengths and polarity, Ala, Leu, Ile, Ser, and Thr. Two computational techniques, long‐time MD simulations and the one‐step perturbation method, were used to obtain free enthalpies of folding. The simulations show that all six peptides exhibit similar folding behavior, and that their dominant fold is the same, i.e., a 314‐helix. Despite the similarities of their structural properties, a small stabilization effect of ca. 2 kJ mol−1 on the folding equilibrium of the 314‐helical structure due to a branching Cγ‐atom in the β3‐side chain is observed. These results confirm those of previous circular dichroism (CD) studies. The length of side chain and its polarity seem to have no apparent (de)stabilization effect. Application of the cost‐effective one‐step perturbation method to predict free‐enthalpy differences appeared to yield an overall accuracy of about kBT, which is not sufficient to detect the small stabilization effect.
Factors controlling spatial and seasonal distributions of precipitation δ18O in China
Authors: Zhao Liangju , Xiao Honglang , Zhou Maoxian , Cheng Guodong , Wang Lixin , Yin Li , Ren Juan
Published: April 2011

Utilising datasets from the Global Network of Isotopes in Precipitation of the International Atomic Energy Agency, and previous isotopic studies, we investigated δ18O spatial and temporal patterns in Chinese precipitation. Significantly positive relationships existed between precipitation δ18O and air temperature above the north of 35°N and in high altitude regions above 32°N. Significantly negative relationships between precipitation δ18O and the precipitation amount existed below south of 35°N. These temperature and precipitation effects became stronger with increasing altitude except in high altitude regions between 32°N and 35°N. The NCEP/NCAR reanalysis data from 1980 to 2004 showed that variations in spatial and seasonal wind fields at 700 hpa and total precipitable water from the ground to the top of the atmosphere were correlated with the monthly spatial distribution of precipitation δ18O. Basing on this relationship, we established quantitative correlations between the mean monthly precipitation δ18O and both latitude and temperature in different seasons. We found that spatial variations in precipitation δ18O could be described well using the Bowen–Wilkinson model and second‐order equations developed during the present study only in winter (from December to February). During the rest of the year, patterns were too complex to predict using simple models. The results suggest that it is difficult to demonstrate variations of precipitation δ18O throughout the year and for all regions of China using a single model. Moreover, the new models for the relationships among precipitation, latitude, and temperature were better able to depict the variations in precipitation δ18O than the Bowen–Wilkinson model. Copyright © 2011 John Wiley & Sons, Ltd.
Adult attachment style and stress as risk factors for early maternal sensitivity and negativity
Authors: Mills‐Koonce W. Roger , Appleyard Karen , Barnett Melissa , Deng Min , Putallaz Martha , Cox Martha
Published: April 2011

The current study examined the individual and joint effects of self‐reported adult attachment style, psychological distress, and parenting stress on maternal caregiving behaviors at 6 and 12 months of child age. We proposed a diathesis‐stress model to examine the potential deleterious effects of stress for mothers with insecure adult attachment styles. Data from 137 mothers were gathered by the longitudinal Durham Child Health and Development Study. Mothers provided self‐reports using C. Hazan and P. Shaver's (1987) Adult Attachment Style measure, the Brief Symptom Inventory (L.R. Derogatis & P.M. Spencer, 1982), and the Parent Stress Inventory (R.R. Abidin, 1995); observations of parenting data were made from 10‐min free‐play interactions. Consistently avoidant mothers were less sensitive with their infants than were consistently secure mothers; however, this effect was limited to avoidant mothers who experienced elevated levels of psychological distress. Results suggest that the association between insecure adult attachment style and insensitive parenting behavior is moderated by concurrent psychosocial stress. Clinical implications for these findings are discussed.
Deconstructing antenatal depression: What is it that matters for neonatal behavioral functioning?
Authors: Goodman Sherryl H. , Rouse Matthew H. , Long Qi , Ji Shuang , Brand Sarah R.
Published: April 2011

This prospective study examined the variability within clinical characteristics of antenatal maternal depression and cortisol levels for associations with newborn infant behavior using the Neonatal Behavioral Assessment Scale (NBAS; T.B. Brazelton, 1984). Participants were 81 pregnant women at risk for perinatal depression given their histories of depression prior to pregnancy. We took into consideration not only whether the woman experienced antenatal depression but also whether the depression met diagnostic criteria and variability in timing (onset and occurrence) of antenatal depression and symptom severity. Infants of mothers who became depressed during pregnancy scored less optimally on a subset of the NBAS scales, specifically those scales related to infant neuroregulation. Among the clinical characteristics of depression, the fetus' overall exposure to mothers' depression (reflected in the mean) was most often and most strongly associated with NBAS scales. In terms of timing, third‐trimester exposure was significantly related to newborn behavior. The findings are discussed within the S.H. Goodman and I.H. Gotlib (1999) model for transmission of psychopathology to offspring of depressed mothers.
Which preventive interventions effectively enhance depressed mothers' sensitivity? A meta‐analysis
Authors: Kersten‐Alvarez Laura E. , Hosman Clemens M.H. , Riksen‐Walraven J. Marianne , Van Doesum Karin T.M. , Hoefnagels Cees
Published: April 2011

Improving depressed mothers' sensitivity is assumed to be a key element in preventing adverse outcomes for children of such mothers. This meta‐analysis examines the short‐term effectiveness of preventive interventions in terms of enhancing depressed mothers' sensitivity toward their child and investigates what type of intervention is most effective. Thirteen interventions, reported in 10 controlled outcome studies, met the inclusion criteria (N = 918). Meta‐analytic results showed a small to medium, significant mean effect size (g = 0.32) with large variation in individual effect sizes (−0.56–1.76). Interventions including baby massage were highly effective in improving maternal sensitivity (g = 0.85). In contrast, individual therapy for the mother proved ineffective in terms of improving maternal sensitivity (g = −0.00). Two other significant predictors of greater effect sizes were the inclusion of a support group and the use of a higher number of intervention methods; however, the significance of these results was largely accounted for by one single study. Our meta‐analysis confirms that depressed mothers' sensitivity can be improved by preventive intervention and suggests that baby massage may be an effective intervention method to evoke short‐term changes in maternal sensitivity. It is unclear whether these changes are maintained over time.
A randomized controlled trial of mother–infant psychoanalytic treatment: II. Predictive and moderating influences of qualitative patient factors
Authors: Salomonsson Björn , Sandell Rolf
Published: April 2011

A randomized control trial was performed on 75 dyads in Stockholm, Sweden, with infants under 1½ years. It recruited mothers who worried about the babies, themselves as mothers, and/or the mother–baby relationship. Two groups of mother–infant dyads were compared. One received only Child Health Centre care (the “CHCC” group) while the other received mother–infant psychoanalytic treatment plus CHCC (the “MIP” group). Significant treatment effects were found on mother‐reported depression, interviewer‐rated dyadic relationship qualities and externally rated maternal sensitivity, and near‐significant effects on mother‐reported stress, all in favor of MIP. The objective of this study is to investigate the predictive and moderating influences on outcomes by qualitatively assessed maternal and infant characteristics. The qualitative factors covered maternal suitability for psychoanalysis, and “ideal types” of mother and child, respectively. Outcome measures from two interviews with a 6‐month interval were depression (Edinburgh Postnatal Depression Scale (J. Cox, J. Holden, & R. Sagovsky, 1987), stress (Swedish Parental Stress Questionnaire (M. Östberg, B. Hagekull, & S. Wettergren, 1997), distress (Swedish Symptom Checklist‐90 (SCL‐90; L.R. Derogatis, 1994; M. Fridell, Z. Cesarec, M. Johansson, & S. Malling Thorsen, 2002) and infant social and emotional functioning (Ages and Stages Questionnaire: Social–Emotional (J. Squires, D. Bricker, K. Heo, & E. Twombly, 2002), relationship qualities (Parent–Infant Global Assessment Scale (PIR‐GAS; ZERO TO THREE, 2005), and videotaped interactions (Emotional Availability Scales, Z. Biringen, J.L. Robinson, & R.N. Emde, 1998). Suitability for psychoanalysis predicted outcome only on the PIR‐GAS. Two overarching maternal ideal types were created, reflecting their attitude to the psychoanalytic process: “Participators” and “Abandoned.” The Participators benefited more from MIP than they did from CHCC on maternal interactive sensitivity. A contrasting, but nonsignificant, pattern was found among the Abandoned mothers. Two ideal types of babies emerged: those “Affected” and “Unaffected” by the disturbance, respectively. Among Affected babies, dyadic relationships and sensitivity among their mothers improved significantly more from MIP than they did from CHCC. The superior effects of MIP applied especially to Participator mothers and Affected infants. For Abandoned mothers and Unaffected infants, CHCC seemed to be of equal value.
Protein coadaptation and the design of novel approaches to identify protein–protein interactions
Authors: Fares Mario A. , Ruiz‐González Mario X. , Labrador Juan Pablo
Published: April 2011

Proteins rarely function in isolation but they form part of complex networks of interactions with other proteins within or among cells. The importance of a particular protein for cell viability is directly dependent upon the number of interactions where it participates and the function it performs: the larger the number of interactions of a protein the greater its functional importance is for the cell. With the advent of genome sequencing and “omics” technologies it became feasible conducting large‐scale searches for protein interacting partners. Unfortunately, the accuracy of such analyses has been underwhelming owing to methodological limitations and to the inherent complexity of protein interactions. In addition to these experimental approaches, many computational methods have been developed to identify protein–protein interactions by assuming that interacting proteins coevolve resulting from the coadaptation dynamics between the amino acids of their interacting faces. We review the main technological advances made in the field of interactomics and discuss the feasibility of computational methods to identify protein–protein interactions based on the estimation of coevolution. As proof‐of‐concept, we present a classical case study: the interactions of cell surface proteins (receptors) and their ligands. Finally, we take this discussion one step forward to include interactions between organisms and species to understand the generation of biological complexity. Development of technologies for accurate detection of protein–protein interactions may shed light on processes that go from the fine‐tuning of pathways and metabolic networks to the emergence of biological complexity. © 2011 IUBMB IUBMB Life, 63(4): 264–271, 2011
Human dental pulp progenitor cell behavior on aqueous and hexafluoroisopropanol based silk scaffolds
Authors: Zhang Weibo , Ahluwalia Ivy Pruitt , Literman Robert , Kaplan David L. , Yelick Pamela C.
Published: April 2011

Silk scaffolds have been successfully used for a variety of tissue engineering applications due to their biocompatibility, diverse physical characteristics, and ability to support cell attachment and proliferation. Our prior characterization of 4‐day postnatal rat tooth bud cells grown on hexafluoro‐2‐propanol (HFIP) silk scaffolds showed that the silk scaffolds not only supported osteodentin formation, but also guided the size and shape of the formed osteodentin. In this study, interactions between human dental pulp cells and HFIP and aqueous based silk scaffolds were studied under both in vitro and in vivo conditions. Silk scaffold porosity and incorporation of RGD and DMP peptides were examined. We found that the degradation of aqueous based silk is much faster than HFIP based silk scaffolds. Also, HFIP based silk scaffolds supported the soft dental pulp formation better than the aqueous based silk scaffolds. No distinct hard tissue regeneration was found in any of the implants, with or without additional cells. We conclude that alternative silk scaffold materials, and hDSC pre‐seeding cell treatments or sorting and enrichment methods, need to be considered for successful dental hard tissue regeneration. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011.
Hydrophilized 3D porous scaffold for effective plasmid DNA delivery
Authors: Oh Se Heang , Kim Tae Ho , Jang Sung Hwan , Im Gun Il , Lee Jin Ho
Published: April 2011

In this study, hydrophilic PLGA/Pluronic F127 scaffolds loaded with a pDNA/PEI‐PEG complex were prepared to estimate their potential use as a polymeric matrix for pDNA delivery. The scaffold was fabricated by a novel precipitation/particulate leaching method. The prepared pDNA/PEI‐PEG complex‐loaded PLGA/Pluronic F127 scaffold exhibited a highly porous (porosity, 93–95%) and open pore structure, as well as hydrophilicity, which can provide the good environment for cell adhesion and growth. The pDNA/PEI‐PEG complexes were efficiently loaded into the PLGA/Pluronic F127 scaffold and continuously released from the scaffolds up to ∼90% of the initial loading amount over a period of 8 wk, which may lead to continuous gene transfection into human bone marrow mesenchymal stem cells (hBMMSCs). From the in vitro cell culture in the scaffolds for transfection, it was observed that the pDNA/PEI‐PEG complex‐loaded hydrophilic PLGA/Pluronic F127 scaffold has a higher transfection efficiency of the pDNA/PEI‐PEG complexes into hBMMSCs than the hydrophobic PLGA ones. The cell viability associated with the pDNA/PEI‐PEG complexes released from the PLGA/Pluronic F127 scaffold was not significantly different from that of the PLGA/Pluronic F127 scaffold without pDNA, indicating its low cytotoxicity, probably due to the sustained release of the pDNA/PEI‐PEG complex from the scaffolds. From these results, we could suggest that the pDNA/PEI‐PEG complex‐loaded hydrophilic PLGA/Pluronic F127 scaffold can be an effective gene delivery system for 3D tissue formation. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011.
Controlling neurite outgrowth with patterned substrates
Authors: Yang In Hong , Co Carlos C. , Ho Chia‐Chi
Published: April 2011

In vivo, neurons form neurites, one of which develops into the axon while others become dendrites. While this neuritogenesis process is well programmed in vivo, there are limited methods to control the number and location of neurite extension in vitro. Here we report a method to control neuritogenesis by confining neurons in specific regions using cell resistant poly(oligoethyleneglycol methacrylate‐co‐methacrylic acid (OEGMA‐co‐MA)) or poly(ethyleneglycol‐block‐lactic acid) PEG‐PLA. Line patterned substrates reduce multiple extension of neurites and stimulate bi‐directional neurite budding for PC12 and cortical neurons. PC12 cells on 20 and 30 μm line patterns extended one neurite in each direction along the line pattern while cortical neuron on 20 and 30 μm line patterns extended one or two neurites in each direction along the line pattern. Statistical analysis of neurite lengths revealed that PC12 cells and cortical neurons on line patterns extend longer neurites. The ability to guide formation of neurites on patterned substrates is useful for generating neural networks and promoting neurite elongation. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011.
Assessment of TD‐DFT‐ and TD‐HF‐based approaches for the prediction of exciton coupling parameters, potential energy curves, and electronic characters of electronically excited aggregates
Authors: Liu Wenlan , Settels Volker , Harbach Philipp H. P. , Dreuw Andreas , Fink Reinhold F. , Engels Bernd
Published: April 2011

The reliability of linear response approaches such as time‐dependent Hartree–Fock (TD‐HF) and time‐dependent density functional theory (TD‐DFT) for the prediction of the excited state properties of 3,4;9,10‐tetracarboxylic‐perylene‐bisimide (PBI) aggregates is investigated. A dimer model of PBI is investigated as a function of a torsional motion of the monomers, which was shown before to be an important intermolecular coordinate in these aggregates. The potential energy curves of the ground state and the two energetically lowest neutral excited and charge‐transfer (CT) states were obtained with the spin‐component scaling modification of the approximate coupled‐cluster singles‐and‐doubles (SCS‐CC2) method as a benchmark for dispersion corrected TD‐HF and a range of TD‐DFT approaches. The highly accurate SCS‐CC2 results are used to assess the other, computationally less demanding methods. TD‐HF predicts similar potential energy curves and transition dipole moments as SCS‐CC2, as well as the correct order of neutral and CT states. This supports an exciton trapping mechanism, which was found on the basis of TD‐HF data. However, the investigated TD‐DFT methods provide generally the opposite character for the excited states. As a consequence, these TD‐DFT results have unacceptably large errors for optical properties of these dye aggregates. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011
Probing the structural and electronic effects to stabilize nonplanar forms of thioamide derivatives: A computational study
Authors: Kesharwani Manoj K. , Ganguly Bishwajit
Published: April 2011

Density functional calculations have been performed to examine the stability of nonplanar conformations of thioamide derivatives. Electrostatic, orbital, and ring strain effects were invoked to stabilize the nonplanar conformations of thioamide systems 2–7. Electrostatic interactions helped to achieve the twisted forms of thioamide derivatives; however, pyramidal forms predicted to be the global minimum. Negative hyperconjugative type interactions enhanced the stability of the twisted form 4b when compared with the planar form 4a. The influence of ring strain effect to achieve the twisted form of thioamide was observed with azirine ring. The predictions made with B3LYP/cc‐pVDZ+ level of theory was found to be in good agreement with more accurate CBS‐QB3 method. The solvent calculations performed with polarized continuum solvation model suggest that the relative stabilities of the nonplanar forms of thioamide derivatives are in general similar to the gas phase results. The importance of hydrogen bonding interactions between the solvent molecules and thioamide derivatives was observed toward the enhanced stability of twisted forms using a combination of explicit solvent molecules and continuum model. The natural bond orbital analysis confirmed the participation of nN → π*CS delocalizations in the planar forms and corroborated the earlier reports on larger delocalizations in thioamide systems. Furthermore, the influence of electrostatic and ring strain effects on the amide, natural amides, and selenoamide has also been studied. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011
Effects of epidermal growth factor and erythropoietin on Müller glial activation and phenotypic plasticity in the adult mammalian retina
Authors: Nickerson P.E.B. , McLeod M.C. , Myers T. , Clarke D.B.
Published: April 2011

Retinal Müller glia have received considerable attention with regard to their potential to function as quiescent retinal precursors. Various activation strategies induce characteristic features of retinal progenitor cells in Müller glia; however, these are often accompanied by hallmark features of reactive gliosis. We investigated the effects of an intravitreal injection of epidermal growth factor (EGF), a known mitogen, and erythropoietin (EPO) on activation and expression of developmental phenotypes within the adult retina. Using thymidine‐analogue labeling as well as immunocytochemical and confocal analyses, we assayed the responses of retinal cells exposed to intravitreal administration of either EGF or EPO. We report that adult Müller glia incorporate bromodeoxyuridine (BrdU) and undergo a process of nuclear translocation to ectopic retinal layers following exposure to EGF. These cells survive within the retina for at least 23 days and express the developmental markers Pax6 and Chx10 as well as nestin and glial fibrillary acidic protein. Furthermore, we demonstrate that cotreatment with EGF and EPO suppresses aspects of EGF‐induced glial reactivity, alters the retinal distribution of BrdU‐positive nuclei, and serves to regulate the expression of developmental phenotypes seen in these cells. These data further our understanding of Müller cell responsiveness to intravitral, combinatorial growth factor treatments. © 2011 Wiley‐Liss, Inc.
Interleukin‐1β stimulates stromal‐derived factor‐1α expression in human subacromial bursa
Authors: Blaine Theodore A. , Cote Mindy A. , Proto Al , Mulcahey Mary , Lee Francis Y. , Bigliani Louis U.
Published: April 2011

Chemokines produced by synoviocytes of the subacromial bursa are up‐regulated in subacromial bursitis and rotator cuff disease. We hypothesized that SDF‐1α production in bursal synoviocytes may be induced by local cytokines such as interleukin IL‐1β and IL‐6. Subacromial bursa specimens were obtained from patients undergoing shoulder surgery. Bursal specimens were stained with anti‐human antibodies to IL‐1, IL‐6, and SDF‐1α by immunohistochemistry and compared to normal and rheumatoid controls. Bursal cells were also isolated from specimens and cultured. Early passaged cells were then treated with cytokines (IL‐1β and IL‐6) and SDF‐1α expression was measured by ELISA and RT‐PCR. SDF‐1α, IL‐1β, and IL‐6 were expressed at high levels in bursitis specimens from human subacromial bursa compared to normal controls. In cultured bursal synoviocytes, there was a dose‐dependent increase in SDF‐1α production in the supernatants of cells treated with IL‐1β. SDF‐1α mRNA expression was also increased in bursal cells treated with IL‐1β. IL‐6 caused a minimal but not statistically significant increase in SDF‐1α expression. SDF‐1α, IL‐1β, and IL‐6 are expressed in the inflamed human subacromial bursal tissues in patients with subacromial bursitis. In cultured bursal synoviocytes, SDF‐1α gene expression and protein production are stimulated by IL‐1β. IL‐1β produced by bursal syvoviocytes and inflammatory cells in the human subacromial bursa is an important signal in the inflammatory response that occurs in subacromial bursitis and rotator cuff disease. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1695–1699, 2011
The weighted optimal common shape technique improves identification of the hip joint center of rotation in vivo
Authors: Heller Markus O. , Kratzenstein Stefan , Ehrig Rainald M. , Wassilew Georgi , Duda Georg N. , Taylor William R.
Published: April 2011

Functional methods present a promising approach for the identification of skeletal kinematics, but their accuracy is limited by soft tissue artifacts (STAs). We hypothesized that consideration of the nonuniform distribution of STAs across the segment can lead to a significant improvement in the determination of the center of rotation at the hip. Twenty‐four total hip arthroplasty (THA) patients performed repetitions of a star‐arc movement. The location of the hip centers of rotation (CoRs) were estimated from the motion data using the Symmetrical Center of Rotation Estimation (SCoRE), both with and without procedures to minimize the effect of STAs. The precision of the CoR estimations was evaluated using the SCoRE residual, a measure of joint precision. Application of the newly developed weighted Optimal Common Shape Technique (wOCST) achieved the best CoR estimations with a precision of better than 3 mm, while the precision using raw data alone was up to seven times worse. Furthermore, consideration of the nonuniform distribution of STA across the surface of the skin using the wOCST produced an improvement of ∼24% over kinematics data processed using the standard OCST. Functional determination of the CoR at the hip using the newly developed wOCST can now identify the joint CoR with a precision of millimeters. Such approaches therefore offer improved precision in the assessment of skeletal kinematics and may aid in evaluating clinical treatment success and differentiating between therapy outcomes. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1470–1475, 2011
Stem labeling results in different patterns of 14C rhizorespiration and 15N distribution in plants compared to natural assimilation pathways
Authors: Wichern Florian , Andreeva Darima , Joergensen Rainer Georg , Kuzyakov Yakov
Published: April 2011

To investigate C and N rhizodeposition, plants can be 13C‐15N double‐labeled with glucose and urea using a stem‐feeding method (wick method). However, it is unclear how the 13C applied as glucose is released into the soil as rhizorespiration in comparison with the 13C applied as CO2 using a natural uptake pathway. In the present study, we therefore compared the short‐term fate of 14C and 15N in white lupine and pea plants applied either by the wick method or the natural pathways of C and N assimilation. Plants were pulse‐labeled in 14CO2‐enriched atmosphere and 15N urea was applied to the roots (atmosphere–soil) following the natural assimilation pathways, or plants were simultaneously labeled with 14C and 15N by applying a 14C glucose–15N urea solution into the stem using the wick method. Plant development, soil microbial biomass, total rhizorespiration, and distribution of N in plants were not affected by the labeling method used but by plant species. However, the 15N : N ratio in plant parts was significantly (p < 0.05) affected by the labeling method, indicating more homogeneous 15N enrichment of plants labeled via root uptake. After 14CO2 atmosphere labeling of plants, the cumulated 14CO2 release from roots and soil showed the common saturation dynamics. In contrast, after 14C‐glucose labeling by the wick method, the cumulated 14CO2 release increased linearly. These results show that 14C applied as glucose using the wick method is not rapidly transferred to the roots as compared to a short‐term 14CO2 pulse. This is partly due to a slower 14C uptake and partly due to slow distribution within the plant. Consequently, 14C‐glucose application by the wick method is no pulse‐labeling approach. However, the advantages of the wick method for 13C‐15N double labeling for estimating rhizodeposition especially under field conditions requires further methodological research.
The coarse‐soil fraction is the main living space of fungal hyphae in the BhBs horizon of a Podzol
Authors: Koele Nina , Storch Felix , Hildebrand Ernst E.
Published: April 2011

In acidified forest soils, the coarse‐soil fraction is a potential nutrient source. Plant nutrient uptake from the coarse‐soil fraction is aided by ectomycorrhiza. Similarly, (recalcitrant) organic matter (OM) is an important nutrient source largely made plant‐available through (symbiotic) microorganisms, especially in the topsoil. We hypothesized that in a podzol profile, fungal hyphae would concentrate in nutrient hotspots, either OM or the coarse‐soil fraction. Absolute hyphal length, base saturation, and organic‐C content of a Podzol profile were determined in the fine‐earth and coarse‐soil fractions. In the fine‐earth fraction, hyphae were attracted by the organic‐C content and relative high base saturation. In the coarse‐soil fraction of the BhBs horizon, the absolute hyphal length exceeded the hyphal length in the fine earth by factor 3, yet C content and base saturation were lowest. We could not determine to what fungi the hyphae belonged. Most likely ectomycorrhiza, ericoid mycorrhiza and saprotrophic fungi dominate the upper soil layers of this profile and all utilize OM for nutrition. In the deeper mineral horizons and especially in the coarse‐soil fraction, ectomycorrhiza are better adapted than other fungi to harvest nutrients from inorganic sources. Additionally, favorable physical properties may explain the high amount of fungal hyphae in the coarse‐soil fraction of the BhBs horizon. Both the coarse‐soil fraction and deeper mineral soil horizons may play a more active role in microbial nutrient cycling than previously assumed.
A critical appraisal of the premotor symptoms of Parkinson's disease: Potential usefulness in early diagnosis and design of neuroprotective trials
Authors: Lang Anthony E.
Published: April 2011

The neurodegenerative process is well established in Parkinson patients presenting to a physician with early motor signs. There is increasing evidence that a variety of nonmotor features can antedate the typical presentation by many years. As the search for successful disease‐modifying treatment advances, it is logical to consider how this could be applied to patients in the earliest stages of the disease, indeed before motor features develop, with the obvious goal of delaying and even preventing the onset of the motor syndrome. However, many of these nonmotor symptoms are rather nonspecific and are not uncommon in the general population. Being able to identify individuals in whom these features are more likely to represent true premotor Parkinson's disease represents a major challenge. Until widely applicable and reliable biomarkers for the presence of Parkinson's disease‐related pathology are developed (including biomarkers of disease severity and rate of progression), further evaluation of possible premotor features in selected populations will probably serve as the basis for future studies of disease‐modifying therapies. This article will review the current status of premotor symptoms of Parkinson's disease and discuss their potential for early diagnosis and the design of neuroprotective trials. © 2011 Movement Disorder Society
Hepatic steatosis by dietary‐conjugated linoleic acid is accompanied by accumulation of diacylglycerol and increased membrane‐associated protein kinase C ε in mice
Authors: Stout Michael B. , Liu Li‐Fen , Belury Martha A.
Published: April 2011

Scope: Conjugated linoleic acid reduces weight gain and adipose mass while inducing liver enlargement, hepatic steatosis, and insulin resistance in mice. The objective of this study was to determine if hepatic steatosis induced by conjugated linoleic acid would predict for hepatic diacylglycerol accumulation, increased membrane‐associated protein kinase C ε, and hyperglycemia.

Methods and results: Six‐wk‐old C57Bl/6 male mice were fed a high‐saturated fat diet for 3 wk and were then randomized to high‐saturated fat diet with or without conjugated linoleic acid (1.5% wt). Following a 6‐wk intervention, hepatic triacylglycerol, diacylglycerol, membrane‐associated protein kinase C ε, and gluconeogenic gene expression were determined. Fasting glucose was determined at baseline and at the end of the study. Conjugated linoleic acid increased hepatic triacylglycerol and diacylglycerol concentration in association with increased membrane‐associated protein kinase C ε. Diacylglycerol concentration proved to be a better predictor than triacylglycerol concentration for the change from baseline in fasting glucose concentration and final insulin concentration. The increase in diacylglycerol concentration was also associated with increased hepatic gluconeogenic gene expression in conjugated linoleic acid‐treated animals.

Conclusion: Our data suggest that conjugated linoleic acid can initiate the pathophysiology responsible for hepatic insulin resistance. Additional studies are needed to determine if the accumulation of hepatic diacylglycerol by conjugated linoleic acid leads to hepatic insulin resistance.