bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Contexts and Building Social Capital for Collective Action: Three Case Studies of Volunteers in the Context of HIV and AIDS in South Africa
Authors: Gibbs Andrew , Campbell Catherine , Akintola Olagoke , Colvin Christopher
Published: May 2014

Social capital is increasingly conceptualised in academic and policy literature as a panacea for a range of health and development issues, particularly in the context of HIV. In this paper, we conceptualise social capital as an umbrella concept capturing processes including networks, norms, trust and relationships that open up opportunities for participation and collective action that allow communities to address issues of common concern. We specifically outline social capital as comprising three distinct forms: bonding, bridging and linking social capital. Rather than presenting original data, we draw on three well‐documented and previously published case studies of health volunteers in South Africa. We explore how social contexts shape the possibility for the emergence and sustainability of social capital. We identify three cross‐cutting contextual factors that are critical barriers to the emergence of social capital: poverty, stigma and the weakness of external organisations' abilities to support small groups. Our three case studies suggest that the assumption that social capital can be generated from the ground upwards is not reasonable. Rather, there needs to be a greater focus on how those charged with supporting small groups—non‐governmental organisations, bureaucracies and development agencies—can work to enable social capital to emerge. Copyright © 2014 John Wiley & Sons, Ltd.
Asymmetric Stereodivergent Strategy Towards Aminocyclitols
Authors: Trost Barry M. , Malhotra Sushant
Published: May 2014

A concise asymmetric synthesis of aminocyclitols, such as diastereomeric 2‐deoxystreptamine analogues and conduramine A, is described. The Pd‐catalyzed asymmetric desymmetrization of meso 1,4‐dibenzolate enables the synthesis of highly oxidized cyclohexane architectures. These scaffolds can potentially be used to access new aminoglycoside antibiotics and enantiomerically pure α‐glucosidase inhibitors.
Longitudinal Changes in Water Quality to Landscape Gradients Along Sha River Basin
Authors: Wen Teng , Sheng Sheng , Xu Chi , Xu Delin , Wan Yun , An Shuqing
Published: May 2014

Both lateral and longitudinal scales are critical to understand the response of stream ecosystem to landscape changes. After acknowledged the most effective lateral scale in previous study, the aim of our study was to investigate the characteristic reaches explaining water quality most and construct dose–response curves to predict water quality changes along the longitudinal scale of Sha River Basin. Results showed that most water quality values at headwater sites were apparently better than those at middle and lower reaches (p < 0.05). Sites at middle or lower reaches are more responsible for water quality deterioration, especially those reaches where towns and cities located. Urbanization is the primary cause, in spite of that the dominant land type in Sha River Basin is agriculture. Response curves of the two major water eutrophication variables (total nitrogen and ammonium) at Sha River Basin both exhibited obvious positive relationships with increasing urbanization, and the response to urbanization gradients was more profound (parabolic curve). According to the Chinese State Standard max permissible limit for drinking and surface water, lower urban land percentage (<20%) was appropriate for keeping water quality from further degradation. All results indicate that quantifying the relationship between water quality and landscape pattern at longitudinal scale may provide a useful tool for determining thresholds where stream health declines and offer constructive suggestions for effective stream restoration.
Phytol Derivatives as Drug Resistance Reversal Agents
Authors: Upadhyay Harish C. , Dwivedi Gaurav R. , Roy Sudeep , Sharma Ashok , Darokar Mahendra P. , Srivastava Santosh K.
Published: May 2014

Phytol was chemically transformed into fifteen semi‐synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with nalidixic acid against E. coli strains CA8000 and DH5α. The pivaloyl (4), 3,4,5‐trimethoxybenzoyl (9), 2,3‐dichlorobenzoyl (10), cinnamoyl (11), and aldehyde (14) derivatives of phytol ((2E,7R,11R)‐3,7,11,15‐tetramethyl‐2‐hexadecen‐1‐ol) were evaluated by using another antibiotic, tetracycline, against the MDREC‐KG4 clinical isolate of E. coli. Derivative 4 decreased the maximal inhibitory concentration (MIC) of the antibiotics by 16‐fold, while derivatives 9, 10, 11, and 14 reduced MIC values of the antibiotics up to eightfold against the E. coli strains. Derivatives 4, 9, 10, 11, and 14 inhibited the ATP‐dependent efflux pump; this was also supported by their in silico binding affinity and down‐regulation of the efflux pump gene yojI, which encodes the multidrug ATP‐binding cassette transporter protein. This study supports the possible use of phytol derivatives in the development of cost‐effective antibacterial combinations.
Development of Novel Selective Peptidomimetics Containing a Boronic Acid Moiety, Targeting the 20S Proteasome as Anticancer Agents
Authors: Scarbaci Kety , Troiano Valeria , Ettari Roberta , Pinto Andrea , Micale Nicola , Di Giovanni Carmen , Cerchia Carmen , Schirmeister Tanja , Novellino Ettore , Lavecchia Antonio , Zappalà Maria , Grasso Silvana
Published: May 2014

This paper describes the design, synthesis, and biological evaluation of peptidomimetic boronates as inhibitors of the 20S proteasome, a validated target in the treatment of multiple myeloma. The synthesized compounds showed a good inhibitory profile against the ChT‐L activity of 20S proteasome. Compounds bearing a β‐alanine residue at the P2 position were the most active, that is, 3‐ethylphenylamino and 4‐methoxyphenylamino (R)‐1‐{3‐[4‐(substituted)‐2‐oxopyridin‐1(2H)‐yl]propanamido}‐3‐methylbutylboronic acids (3 c and 3 d, respectively), and these derivatives showed inhibition constants (Ki) of 17 and 20 nM, respectively. In addition, they co‐inhibited post glutamyl peptide hydrolase activity (3 c, Ki=2.57 μM; 3 d, Ki=3.81 μM). No inhibition was recorded against the bovine pancreatic α‐chymotrypsin, which thus confirms the selectivity towards the target enzyme. Docking studies of 3 c and related inhibitors into the yeast proteasome revealed the structural basis for specificity. The evaluation of growth inhibitory effects against 60 human tumor cell lines was performed at the US National Cancer Institute. Among the selected compounds, 3 c showed 50 % growth inhibition (GI50) values at the sub‐micromolar level on all cell lines.
Synthesis and Antisense Properties of 2′‐O‐(2S‐Methoxypropyl)‐RNA‐Modified Gapmer Antisense Oligonucleotides
Authors: Yu Jinghua , Pandey Sanjay K. , Khatri Hetal , Prakash Thazha P. , Swayze Eric E. , Seth Punit P.
Published: May 2014

To ascertain whether increasing hydrophobicity can enhance the activity of second‐generation antisense oligonucleotides (ASOs) in muscle, we investigated the antisense properties of 2′‐O‐(2S‐methoxypropyl)‐RNA (2S‐MOP)‐modified ASOs. Synthesis of the 2S‐MOP 5‐methyl uridine phosphoramidite was accomplished on a multi‐gram scale by Lewis‐acid‐catalyzed ring opening of 5′‐O‐tert‐butyldiphenylsilyl ether‐protected 2,2′‐anhydro‐5‐methyl uridine with 2S‐methoxy‐1‐propanol. Synthesis of the 2S‐MOP 5‐methyl cytidine nucleoside from the corresponding 5‐methyl uridine nucleoside was accomplished by formation and displacement of a 4‐triazolide intermediate with aqueous ammonia. 2S‐MOP‐modified oligonucleotides were prepared on an automated DNA synthesizer and showed similar enhancements in duplex thermal stability as 2′‐O‐methoxyethyl RNA (MOE)‐modified oligonucleotides. 2S‐MOP‐containing antisense oligonucleotides were evaluated in Balb‐c mice and showed good activity for decreasing the expression levels of scavenger receptor B1 (Srb1) and phosphatase and tensin homologue (PTEN) mRNA in liver and muscle tissue.
Patient‐centered research to inform patient‐centered care for adolescents and young adults (AYAs) with cancer
Authors: Zebrack Brad
Published: May 2014

The studies by Salsman et al and Champion et al stimulate important dialogue related to investigations of sex, sexuality, and the interdependence of relationships, emotional health, and physical functioning for adolescents and young adults (AYAs) with cancer. Specifically, their findings are salient to discussions of what the upper and lower age bounds could or should be to define an AYA population, and raise unique methodological issues related to cancer genetics and assessments of AYA family composition, gender identification, marital and relationship status, and sex and sexuality.
Premature ovarian failure is a major risk factor for cancer‐related sexual dysfunction
Authors: Schover Leslie R.
Published: May 2014

Premature ovarian failure is a major risk factor for sexual dysfunction in women who receive treatment for premenopausal breast cancer. Women should be counseled on prevention of vulvovaginal dryness and atrophy when chemotherapy is initiated.
Comparison of younger and older breast cancer survivors and age‐matched controls on specific and overall quality of life domains
Authors: Champion Victoria L. , Wagner Lynne I. , Monahan Patrick O. , Daggy Joanne , Smith Lisa , Cohee Andrea , Ziner Kim W. , Haase Joan E. , Miller Kathy D. , Pradhan Kamnesh , Unverzagt Frederick W. , Cella David , Ansari Bilal , Sledge George W.
Published: May 2014

BACKGROUND

Younger survivors (YS) of breast cancer often report more survivorship symptoms such as fatigue, depression, sexual difficulty, and cognitive problems than older survivors (OS). This study sought to determine the effect of breast cancer and age at diagnosis on quality of life (QoL) by comparing 3 groups: 1) YS diagnosed at age 45 years or before, 2) OS diagnosed between 55 and 70, and 3) for the YSs, age‐matched controls (AC) of women not diagnosed with breast cancer.

METHODS

Using a large Eastern Cooperative Oncology Group (ECOG) database, 505 YS were recruited who were aged 45 years or younger when diagnosed and 622 OS diagnosed at 55 to 70 years of age. YS, OS, and AC were compared on physical, psychological, social, spiritual, and overall QoL variables.

RESULTS

Compared to both AC and to OS, YS reported more depressive symptoms (P = .005) and fatigue (P < .001), poorer self‐reported attention function (P < .001), and poorer sexual function (P < .001) than either comparison group. However, YS also reported a greater sense of personal growth (P < .001) and perceived less social constraint (P < .001) from their partner than AC.

CONCLUSIONS

YS reported worse functioning than AC relative to depression, fatigue, attention, sexual function, and spirituality. Perhaps even more important, YS fared worse than both AC and OS on body image, anxiety, sleep, marital satisfaction, and fear of recurrence, indicating that YS are at greater risk for long‐term QoL problems than survivors diagnosed at a later age.Cancer2014;120:2237–2246.©2014 American Cancer Society.
Treatment‐related amenorrhea and sexual functioning in young breast cancer survivors
Authors: Rosenberg Shoshana M. , Tamimi Rulla M. , Gelber Shari , Ruddy Kathryn J. , Bober Sharon L. , Kereakoglow Sandra , Borges Virginia F. , Come Steven E. , Schapira Lidia , Partridge Ann H.
Published: May 2014

BACKGROUND

Sexual dysfunction is a known complication of adjuvant therapy for breast cancer and an important determinant of quality of life. However, few studies have explored how treatment and other factors affect sexual functioning in young breast cancer survivors.

METHODS

Four hundred sixty‐one premenopausal women with stage 0 through III breast cancer were surveyed an average of 1 year after diagnosis as part of a prospective cohort study of women who were aged ≤40 years at diagnosis. Sexual interest and dysfunction were assessed using the Cancer Rehabilitation Evaluation System (CARES). Mean CARES scores were compared and multiple regression models were fit to assess treatment and a range of menopausal and somatic symptoms in relation to sexual functioning.

RESULTS

Mean CARES sexual interest and dysfunction scores were both highest (indicating poorer functioning) among women who received chemotherapy and were amenorrheic from treatment. After accounting for menopausal and somatic symptoms, treatment‐associated amenorrhea remained associated with decreased interest but was no longer an independent predictor of dysfunction. In the multivariable analysis, independent predictors of dysfunction included vaginal pain symptoms, poorer body image, and fatigue. Sexual interest was associated with vaginal pain symptoms, body image, and weight problems.

CONCLUSIONS

Factors associated with decreased sexual functioning in young breast cancer survivors can often be ameliorated. The current findings have implications for premenopausal women with other types of cancer who might be experiencing amenorrhea because of chemotherapy or surgery. Increased awareness and early intervention is essential to help improve sexual functioning and associated quality of life for all young cancer survivors. [See editorial on pages 000‐000, this issue.] Cancer 2014;120:2264–2271. © 2014 American Cancer Society.
Physical, emotional, and social health differences between posttreatment young adults with cancer and matched healthy controls
Authors: Salsman John M. , Garcia Sofia F. , Yanez Betina , Sanford Stacy D. , Snyder Mallory A. , Victorson David
Published: May 2014

BACKGROUND

Young adults (YAs; ages 18‐39 years) with cancer face interrupted developmental milestones and increased stressors that can adversely influence psychosocial adjustment. Transitioning from active treatment to posttreatment survivorship can be particularly challenging. The purpose of this study is to describe the health‐related quality of life (HRQL) and psychological adaptation of YAs after treatment, relative to young adults without cancer.

METHODS

Three cohorts of YAs of mixed cancer diagnoses (N = 120, 0‐12 months after treatment; N = 102, 13‐24 months after treatment; and N = 113, 25‐60 months after treatment; combined M = 31.8 years old, combined sex = 68% women) and an age‐, education‐, sex‐, and partner status–matched group of healthy control participants (HCs; N = 335) were recruited via an online research panel. All participants completed measures assessing demographic and clinical characteristics, HRQL (physical, emotional, social, and spiritual), and psychological adaptation (anxiety, depression, positive affect, posttraumatic growth). Measure content was slightly modified for applicability to HCs without a cancer history.

RESULTS

Multivariate analysis of covariance found a significant main effect for group (YAs versus HCs) and a significant group‐by‐cohort interaction. YAs reported poorer physical (P = .005, d = .22) and emotional well‐being (P = .011, d = .20) but better social well‐being (P < .001, d = .49). YAs reported comparatively stable scores (P = .74) for posttraumatic growth compared to HCs, who reported greater posttraumatic growth across cohorts (P = .01, d = 16).

CONCLUSIONS

Findings underscore the negative and positive sequelae for YAs and highlight the need for comprehensive assessment among YA survivors of cancer. A matched, HC group allows the HRQL and psychological adaptation of YAs to be placed in context, enabling a more precise determination of the impact of cancer on YAs. Cancer 2014;120:2247–2254. © 2014 American Cancer Society.
Patient‐oncologist alliance as protection against suicidal ideation in young adults with advanced cancer
Authors: Trevino Kelly M. , Abbott Caroline H. , Fisch Michael J. , Friedlander Robert J. , Duberstein Paul R. , Prigerson Holly G.
Published: May 2014

BACKGROUND

Young adults with cancer are at an increased risk of suicidal ideation. To the authors' knowledge, the impact of the patient‐oncologist alliance on suicidal ideation has not been examined to date. The current study examined the relationship between the patient‐oncologist therapeutic alliance and suicidal ideation in young adults with advanced cancer.

METHODS

A total of 93 young adult patients (aged 20 years‐40 years) with incurable, recurrent, or metastatic cancer were evaluated by trained interviewers. Suicidal ideation was assessed with the Yale Evaluation of Suicidality scale, dichotomized into a positive and negative score. Predictors included diagnoses of major depressive disorder and posttraumatic stress disorder, physical quality of life, social support, and use of mental health and supportive care services. The Human Connection Scale, dichotomized into a strong (upper third) and weak (lower two‐thirds) therapeutic alliance, assessed the strength of the patients' perceived oncologist alliance.

RESULTS

Approximately 22.6% of patients screened positive for suicidal ideation. Patients with a strong therapeutic alliance were found to be at reduced risk of suicidal ideation after controlling for confounding influences of cancer diagnosis, Karnofsky performance status, number of physical symptoms, physical quality of life, major depressive disorder, posttraumatic stress disorder, and social support. A strong therapeutic alliance was also associated with a reduced risk of suicidal ideation after controlling for mental health discussions with health care providers and use of mental health interventions.

CONCLUSIONS

The patient‐oncologist alliance was found to be a robust predictor of suicidal ideation and provided better protection against suicidal ideation than mental health interventions, including psychotropic medications. Oncologists may significantly influence patients' mental health and may benefit from training and guidance in building strong alliances with their young adult patients. Cancer 2014;120:2272–2281. © 2014 American Cancer Society.
Factors associated with reduced accuracy in Papanicolaou tests for patients with invasive cervical cancer
Authors: Zhao Lichao , Wentzensen Nicolas , Zhang Roy R. , Dunn S. Terence , Gold Michael A. , Wang Sophia S. , Schiffman Mark , Walker Joan L. , Zuna Rosemary E.
Published: May 2014

BACKGROUND

Recent proposals to lengthen the interval in cervical cancer screening highlight the importance of the accurate interpretation of screening tests. Tumor debris present in Papanicolaou (Pap) tests from women with invasive cancer is known to hamper interpretation. The current study evaluated limiting factors in Pap tests from women with invasive cervical cancer.

METHODS

A total of 3003 women with the spectrum of cervical lesions who had ThinPrep (Hologic Inc, Marlborough, Mass) Pap and human papillomavirus (HPV) genotyping tests performed were grouped by their most severe histologic diagnosis. Cytologic and HPV results were analyzed by cross‐sectional analysis.

RESULTS

The unsatisfactory rate of cytology specimens from patients with cancer (3.1%) was significantly higher than those from patients with cervical intraepithelial neoplasia of type 3 or less (0.8%) (P < .001). The percentage of samples with qualified adequacy was 34.8% in specimens from patients with cancer compared with only 3.6% from specimens from those without cancer (P < .001). The unsatisfactory and qualified adequacy rates were higher in squamous cancers compared with adenocarcinomas. However, adenocarcinomas were identified less frequently than squamous cancers (37.0% vs 61.7%) in the Pap tests. HPV tests were positive in 84.4% of unsatisfactory cases including 8 of 9 cancer cases, although 8.5% of cancers tested negative for HPV.

CONCLUSIONS

Unsatisfactory and suboptimal ThinPrep Pap tests were increased in cancer cases compared with lesser histologic diagnoses. This was found to be particularly true for squamous cancers. Specimens from adenocarcinomas had fewer adequacy problems but were less frequently recognized as malignant. HPV tests were positive in the majority of unsatisfactory Pap tests in women with carcinoma, suggesting that HPV testing in women aged > 30 years can help to identify high‐risk women with unsatisfactory Pap tests. Cancer (Cancer Cytopathol) 2014;122:694–701. © 2014 American Cancer Society.
Are Boryl Radicals from Amine–Boranes and Phosphine–Boranes the Most Stable Radicals?
Authors: Martín‐Sómer Ana , Mó Otilia , Yáñez Manuel
Published: May 2014

The relative stability of the radicals that can be produced from amine–boranes and phosphine–boranes is investigated at the G3‐RAD level of theory. Aminyl ([RNH].:BH3) and phosphinyl ([RPH].:BH3) radicals are systematically more stable than the boryl analogues, [RNH2]:BH2. and [RPH2]:BH2.. Despite similar stability trends for [RNH].:BH3 and [RPH].:BH3 radicals with respect to boryl radicals, there are significant dissimilarities between amine– and phosphine–boranes. The homolytic bond dissociation energy of the NH bond decreases upon association of the amines with BH3, whereas that of the PH bond for phosphines increases. The stabilization of the free amine is much smaller than that of the corresponding aminyl radical, whereas for phosphines this is the other way around. The homolytic bond dissociation energy of the BH bond of borane decreases upon complexation with both amines and phosphines.
Efficient Fixation of CO2 by a Zinc‐Coordinated Conjugated Microporous Polymer
Authors: Xie Yong , Wang Ting‐Ting , Yang Rui‐Xia , Huang Nian‐Yu , Zou Kun , Deng Wei‐Qiao
Published: May 2014

Zinc‐coordinated conjugated microporous polymers (Zn‐CMPs), prepared by linking salen zinc and 1,3,5‐triethynylbenzene, exhibit extraordinary activities (turnover frequencies of up to 11600 h−1), broad substrate scope, and group tolerance for the synthesis of functional organic carbonates by coupling epoxides with CO2 at 120 °C and 3.0 MPa without the use of additional solvents. The catalytic activity of Zn‐CMP is comparable to those of homogeneous catalysts and superior to those of other heterogeneous catalysts. This catalyst could be reused more than ten times without a significant decrease in performance.
Concentration‐dependent effects of WNTLESS on WNT1/3A signaling
Authors: Galli Lisa M. , Szabo Linda A. , Li Lydia , Htaik Yin Min , Onguka Ouma , Burrus Laura W.
Published: May 2014

Background: WNTLESS (WLS) is a multi‐transmembrane protein that transports Wnt ligands from the Golgi to the cell surface. Although WLS loss‐of‐function experiments in the developing central nervous system reveal phenotypes consistent with defects in WNT1 and WNT3A signaling, data from complementary gain‐of‐function experiments have not yet been reported. Here, we report the phenotypic consequences of WLS overexpression in cultured cells and in the developing chick spinal cord. Results: Overexpression of small amounts of WLS along with either WNT1 or WNT3A promotes the Wnt/β‐catenin pathway in HEK293T cells, while overexpression of higher levels of WLS inhibits the Wnt/β‐catenin pathway in these cells. Similarly, overexpressed WLS inhibits the Wnt/β‐catenin pathway in the developing spinal cord, as assessed by cell proliferation and specification. These effects appear to be Wnt‐specific as overexpression of WLS inhibits the expression of FZD10, a target of β‐catenin‐dependent transcription. Conclusions: Our results show that overexpression of WLS inhibits Wnt/β‐catenin signaling in the spinal cord. As the activation of the Wnt/β‐catenin pathway in the spinal cord requires WNT1 or WNT3A, our results are consistent with a model in which the relative concentration of WLS to Wnt regulates WNT1/3A signaling in the developing spinal cord. Developmental Dynamics 243:1095–1105, 2014. © 2014 Wiley Periodicals, Inc.
Copper Complexes of N‐Donor Ligands as Artificial Nucleases
Authors: Wende Christian , Lüdtke Carsten , Kulak Nora
Published: May 2014

Invited for the cover of this issue is the group of Nora Kulak at Freie Universität Berlin. The cover image shows metal complexes capable of cleaving DNA, so‐called artificial metallonucleases based on copper as the central atom and comprising N‐donor ligands. Heteroaromatic, macrocyclic, and peptidic ligand systems are adumbrated in the background.
Introducing Potential Hemilability into “Click” Triazoles and Triazolylidenes: Synthesis and Characterization of d6‐Metal Complexes and Oxidation Catalysis
Authors: Hohloch Stephan , Hettmanczyk Lara , Sarkar Biprajit
Published: May 2014

Hemilabile ligands are known to impart remarkable properties to their metal complexes. Herein, we present arene half‐sandwich complexes of RuII, OsII, and IrIII with “click”‐derived 1,2,3‐triazole (L1) and 1,2,3‐triazol‐5‐ylidene (L2) ligands containing a potentially hemilabile thioether donor. Structural elucidation of the complexes revealed localization of double bonds within the triazole in L1 and a delocalized situation within the triazolylidene ring of L2. For complexes with L1, unusual coordination occurs through the less basic nitrogen “N2” of the 1,2,3‐triazole. All complexes were applied for the catalytic oxidation of benzyl alcohol to benzaldehyde using N‐methylmorpholine N‐oxide as sacrificial oxidant. Furthermore, oxidation of diphenylmethanol to benzophenone was also achieved by using low catalyst loadings in very good yields. These are rare examples of OsII–triazole, as well as of OsII–triazolylidene complexes with “click”‐derived ligands.
Halogenated flame retardants during egg formation and chicken embryo development: Maternal transfer, possible biotransformation, and tissue distribution
Authors: Zheng Xiao-Bo , Luo Xiao-Jun , Zeng Yan-Hong , Wu Jiang-Ping , Chen She-Jun , Mai Bi-Xian
Published: May 2014

Hen muscle, eggs, and newborn chick tissues (muscle and liver) were collected from an electronic waste recycling site in southern China. The authors examined the maternal transfer, potential metabolism, and tissue distribution of several halogenated flame retardants (HFRs) during egg formation and chicken embryo development. The pollutant composition changes significantly from hen muscle to eggs and from eggs to tissues of newborn chicks. Higher-halogenated chemicals, such as octa- to deca-polybrominated diphenyl ether (PBDE) congeners, deca-polybrominated biphenyl (PBB209), and dechlorane plus (DP), are less readily transferred to eggs compared with lower-halogenated chemicals. During embryo development, PBDEs are the most likely to be metabolized, whereas decabromodiphenyl ethane (DBDPE) is the least. The authors also observed selective maternal transfer of anti-DP and stereoselective metabolism of syn-DP during chicken embryo development. During tissue development, liver has greater affinity than the muscle for chemcials with a high log octanol–water partition coefficient, with the exception of DBDPE. The differences in metabolism potential of different chemicals in chicken embryos cause pollutant composition alterations. Halogenated flame retardant from maternal transfer and tissue distribution also exhibited chemical specificity, especially for DBDPE. Levels of DBDPE were elevated along with the full process from hen muscle to eggs and from eggs to chick tissues. More attention should be paid to the selective accumulation and biotransformation of HFRs in the early development stage of birds. Environ Toxicol Chem 2014;33:1712–1719. © 2014 SETAC
Preparation process of active enzymolysis polypeptides from seahorse bone meal
Authors: Jiang Zhanzhi , Xu Yongjian , Su Yuting
Published: May 2014

The preparation process of protein enzymolysis technology for the three‐spot seahorse (Hippocampus trimaculatus Leach) degreased bone meal was developed. Two enzymes with better enzymolysis effect were selected from the five proteases, and the optimization condition of the Alkaline Protease is temperature – 54.7°C, pH – 9, duration of 6 h, the acquired rate of polypeptides was 11.77%; and that of Trypsin is temperature – 45°C, pH – 8.8, and duration of 4 h, and the rate was 11.49% by Response Surface Methodology. The strategy of compound enzymes was “Trypsin + Alkaline Protease”. The selected preparation process of active polypeptides by the compound enzymolysis technology acquired rate of polypeptides was 14.41 ± 0.16%, increased about 3% of acquired rate of polypeptides and 2.6–4.5% of the free radical scavenging rate than those of the single enzyme. The increased antioxidant capacity mainly came from the increased concentration of polypeptide in II# peak, which increased about 10% of the free radical scavenging rate. The strategy of selected compound enzymes can effectively improve the utilization rate of seahorse protein.
Mitochondrial dysfunction in central nervous system white matter disorders
Authors: Morató Laia , Bertini Enrico , Verrigni Daniela , Ardissone Anna , Ruiz Montse , Ferrer Isidre , Uziel Graziella , Pujol Aurora
Published: May 2014

Defects of mitochondrial respiration and function had been proposed as a major culprit in the most common neurodegenerative diseases, including prototypic diseases of central nervous system (CNS) white matter such as multiple sclerosis. The importance of mitochondria for white matter is best exemplified in a group of defects of the mitochondria oxidative metabolism called mitochondria leukoencephalopathies or encephalomyopathies. These diseases are clinically and genetically heterogeneous, given the dual control of the respiratory chain by nuclear and mitochondrial DNA, which makes the precise diagnosis and classification challenging. Our understanding of disease pathogenesis is nowadays still limited. Here, we review current knowledge on pathogenesis and genetics, outlining diagnostic clues for the various forms of mitochondria disease. In particular, we underscore the value of magnetic resonance imaging (MRI) for the differential diagnosis of specific types of mitochondrial leukoencephalopathies, such as genetic defects on SDHFA1. The use of novel technologies for gene identification, such as whole‐exome sequencing studies, is expected to shed light on novel molecular etiologies, broadening prenatal diagnosis, disease understanding, and therapeutic options. Current treatments are mostly palliative, but very promising novel gene and pharmacologic therapies are emerging, which may also benefit a growing list of secondary mitochondriopathies, such as the peroxisomal disease adrenoleukodystrophy. GLIA 2014;62:1878–1894
Activation of sodium‐dependent glutamate transporters regulates the morphological aspects of oligodendrocyte maturation via signaling through calcium/calmodulin‐dependent kinase IIβ's actin‐binding/‐stabilizing domain
Authors: Martinez‐Lozada Zila , Waggener Christopher T. , Kim Karam , Zou Shiping , Knapp Pamela E. , Hayashi Yasunori , Ortega Arturo , Fuss Babette
Published: May 2014

Signaling via the major excitatory amino acid glutamate has been implicated in the regulation of various aspects of the biology of oligodendrocytes, the myelinating cells of the central nervous system (CNS). In this respect, cells of the oligodendrocyte lineage have been described to express a variety of glutamate‐responsive transmembrane proteins including sodium‐dependent glutamate transporters. The latter have been well characterized to mediate glutamate clearance from the extracellular space. However, there is increasing evidence that they also mediate glutamate‐induced intracellular signaling events. Our data presented here show that the activation of oligodendrocyte expressed sodium‐dependent glutamate transporters, in particular GLT‐1 and GLAST, promotes the morphological aspects of oligodendrocyte maturation. This effect was found to be associated with a transient increase in intracellular calcium levels and a transient phosphorylation event at the serine (S)371 site of the calcium sensor calcium/calmodulin‐dependent kinase type IIβ (CaMKIIβ). The potential regulatory S371 site is located within CaMKIIβ's previously defined actin‐binding/‐stabilizing domain, and phosphorylation events within this domain were identified in our studies as a requirement for sodium‐dependent glutamate transporter‐mediated promotion of oligodendrocyte maturation. Furthermore, our data provide good evidence for a role of these phosphorylation events in mediating detachment of CaMKIIβ from filamentous (F)‐actin, and hence allowing a remodeling of the oligodendrocyte's actin cytoskeleton. Taken together with our recent findings, which demonstrated a crucial role of CaMKIIβ in regulating CNS myelination in vivo, our data strongly suggest that a sodium‐dependent glutamate transporter–CaMKIIβ–actin cytoskeleton axis plays an important role in the regulation of oligodendrocyte maturation and CNS myelination. GLIA 2014;62:1543–1558
Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia
Authors: Huang Zirui , Wang Zhiyao , Zhang Jianfeng , Dai Rui , Wu Jinsong , Li Yuan , Liang Weimin , Mao Ying , Yang Zhong , Holland Giles , Zhang Jun , Northoff Georg
Published: May 2014

Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter‐ and intra‐regional neural synchronization and temporal variance of resting state activity in anesthetic‐induced unconsciousness state. Applying an intra‐subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra‐regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency‐dependent effects of SD in the thalamus, which showed abnormally high SD in Slow‐5 (0.01–0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. Hum Brain Mapp 35:5368–5378, 2014. © 2014 Wiley Periodicals, Inc.
Nonlinear bacterial load‐streamflow response on a marine beach
Authors: Thoe Wai , Lee Joseph Hun‐wei
Published: May 2014

Bacterial concentration (Escherichia coli) is used as the key indicator for marine beach water quality in Hong Kong. For beaches receiving streamflow from unsewered catchments, water quality is mainly affected by local nonpoint source pollution and is highly dependent on the bacterial load contributed from the catchment. As most of these catchments are ungauged, the bacterial load is generally unknown. In this study, streamflow and the associated bacterial load contributed from an unsewered catchment to a marine beach, Big Wave Bay, are simulated using a modelling approach. The physically based distributed hydrological model, MIKE‐SHE, and the empirical watershed water quality model (Hydrological Simulation Program – Fortran) are used to simulate streamflow and daily‐averaged E. coli concentration/load, respectively. The total daily derived loads predicted by the model during calibration (June–July 2007) and validation (July–October 2008) periods agree well with empirical validation data, with a percentage difference of 3 and 2%, respectively. The simulation results show a nonlinear relationship between E. coli load and rainfall/streamflow and reveal a source limiting nature of nonpoint source pollution. The derived load is further used as an independent variable in a multiple linear regression (MLR) model to predict daily beach water quality. When compared with the MLR models based solely on hydrometeorological input variables (e.g. rainfall and salinity), the new model based on bacterial load predicts much more realistic E. coli concentrations during rainstorms. Copyright © 2014 John Wiley & Sons, Ltd.
Vascular endothelial growth factor mRNA levels as a biomarker for short‐term N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine‐induced rat bladder carcinogenesis bioassay
Authors: Wakui Shin , Mutou Tomoko , Takahashi Hiroyuki , Ikegami Masahiro , Wanibuchi Hideki , Fukushima Shoji
Published: May 2014

Generically, carcinogenic effects of chemicals in bladder carcinogenesis are judged by induction of papillary or nodular (PN) hyperplasia in rats given N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN) for 4 weeks and the test chemical for 22–28 weeks. However, upregulation of vascular endothelial growth factor (VEGF) begins early in rat BBN bladder carcinogenesis. To establish a short‐term rat bladder carcinogenic bioassay, we analyzed the correlations between VEGF, VEGF mRNA and bladder lesions inductions at 10 and 26 weeks after BBN treatment. Six‐week‐old male Wistar (slc) rats were given 0.05% BBN for 4, 10 or 26 weeks. To avoid individual rat bias, the bladders were investigated by partial cystectomy at 10 weeks and total cystectomy at 26 weeks. After induction, PN hyperplasia and carcinoma in rats increased with the length of BBN treatment and immunohistochemical VEGF expression also increased following carcinogenesis, but the immunoreactivity of individual lesions was quite variable. Moreover, induction of PN hyperplasia at 10 weeks’ BBN treatment was not significantly correlated with that at 26 weeks' treatment; thus, it was not possible to predict the carcinogenic effect due to the induction of PN hyperplasia at 26 weeks' BBN treatment by that at 10 weeks' treatment. However, VEGF mRNA levels of rat bladders at 10 weeks' BBN treatment revealed a strong significant correlation with the incidence of bladder lesions at 26 weeks' treatment. Here, we suggest that quantitative VEGF mRNA levels are a good biomarker for a short‐term BBN‐induced bioassay for rat bladder carcinogenesis. Copyright © 2014 John Wiley & Sons, Ltd.
Developmental toxicity assay using high content screening of zebrafish embryos
Authors: Lantz‐McPeak Susan , Guo Xiaoqing , Cuevas Elvis , Dumas Melanie , Newport Glenn D. , Ali Syed F. , Paule Merle G. , Kanungo Jyotshna
Published: May 2014

Typically, time‐consuming standard toxicological assays using the zebrafish (Danio rerio) embryo model evaluate mortality and teratogenicity after exposure during the first 2 days post‐fertilization. Here we describe an automated image‐based high content screening (HCS) assay to identify the teratogenic/embryotoxic potential of compounds in zebrafish embryos in vivo. Automated image acquisition was performed using a high content microscope system. Further automated analysis of embryo length, as a statistically quantifiable endpoint of toxicity, was performed on images post‐acquisition. The biological effects of ethanol, nicotine, ketamine, caffeine, dimethyl sulfoxide and temperature on zebrafish embryos were assessed. This automated developmental toxicity assay, based on a growth‐retardation endpoint should be suitable for evaluating the effects of potential teratogens and developmental toxicants in a high throughput manner. This approach can significantly expedite the screening of potential teratogens and developmental toxicants, thereby improving the current risk assessment process by decreasing analysis time and required resources. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Gene expression analysis of laminin‐1‐induced neurite outgrowth in human mesenchymal stem cells derived from bone marrow
Authors: Mruthyunjaya S. , Parveen D. , Shah Reecha D. , Manchanda Rumma , Godbole Ravibhushan , Vasudevan Madavan , Shastry Padma
Published: May 2014

The mechanisms underlying the differentiation of Mesenchymal stem cells (MSCs) toward neuronal cell type are not clearly understood. Earlier, we reported that laminin‐1 induces neurite outgrowth in human MSCs via c‐Jun/AP‐1 activation through ERK, JNK, and Akt pathways. In this study, we demonstrate that laminin‐1 increases the expression of proneural gene, neuroD1 and induces the expression of immediate‐early biomarkers of neuronal cell‐programming—Egr1, Egr3, PC3, and PC4. Gene expression profiling of MSCs cultured on laminin‐1 and Poly‐l‐lysine for 12 h revealed differential regulation of 267 genes (>1.5 fold, p < 0.05), predominantly in the category of nervous system development and affected the pathways involved in TGF‐β/TNF‐α signaling, regulation of MAPK and JNK cascade. Data for 11 selected genes related to nervous system development was validated by real time PCR. Transcriptional regulatory network analysis revealed c‐Jun as the key transcription factor regulating majority of differentially expressed genes and identified Disrupted in schizophrenia 1, as a novel target of c‐Jun. Modeling and analysis of biological network showed selective induction of Growth Arrest and DNA damage 45 (GADD45B) and repression of NF‐κB inhibitor A (NFκBIA). Collectively, our findings provide the basis for understanding the molecular mechanisms associated with laminin‐1‐induced neurogenic expression in MSCs. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 746–761, 2015.
Reaction mechanism of Ru(II) piano‐stool complexes: Umbrella sampling QM/MM MD study
Authors: Futera Zdeněk , Burda Jaroslav V.
Published: May 2014

Biologically relevant interactions of piano‐stool ruthenium(II) complexes with ds‐DNA are studied in this article by hybrid quantum mechanics—molecular mechanics (QM/MM) computational technique. The whole reaction mechanism is divided into three phases: (i) hydration of the [RuII(η6‐benzene)(en)Cl]+complex, (ii) monoadduct formation between the resulting aqua‐Ru(II) complex and N7 position of one of the guanines in the ds‐DNA oligomer, and (iii) formation of the intrastrand Ru(II) bridge (cross‐link) between two adjacent guanines. Free energy profiles of all the reactions are explored by QM/MM MD umbrella sampling approach where the Ru(II) complex and two guanines represent a quantum core, which is described by density functional theory methods. The combined QM/MM scheme is realized by our own software, which was developed to couple several quantum chemical programs (in this study Gaussian 09) and Amber 11 package. Calculated free energy barriers of the both ruthenium hydration and Ru(II)‐N7(G) DNA binding process are in good agreement with experimentally measured rate constants. Then, this method was used to study the possibility of cross‐link formation. One feasible pathway leading to Ru(II) guanine‐guanine cross‐link with synchronous releasing of the benzene ligand is predicted. The cross‐linking is an exergonic process with the energy barrier lower than for the monoadduct reaction of Ru(II) complex with ds‐DNA. © 2014 Wiley Periodicals, Inc.
A comparison of low and high activity precatalysts: Do the calculated energy barriers during the self‐metathesis reaction of 1‐Octene correlate with the precatalyst metathesis activity?
Authors: Marx Frans T. I. , Jordaan Johan H. L. , Lachmann Gerhard , Vosloo Hermanus C. M.
Published: May 2014

The self‐metathesis reaction of 1‐octene with several well‐known Grubbs‐type precatalysts and the new Z‐selective Grubbs precatalyst were studied with molecular modeling. The obtained Gibbs‐free energy values for all the steps during the productive metathesis of 1‐octene were compared to the values obtained for some low catalytic activity precatalysts. Determining how the Gibbs‐free energy values of highly active precatalysts compare to that of low catalytic activity precatalysts gave a deeper insight into the mechanism. The questionable correlation of the theoretically observed trends with those obtained experimentally does point to the need to be very cautious when making assumptions from theoretical results without a sufficiently large dataset. © 2014 Wiley Periodicals, Inc.
Visualizing energy landscapes with metric disconnectivity graphs
Authors: Smeeton Lewis C. , Oakley Mark T. , Johnston Roy L.
Published: May 2014

The visualization of multidimensional energy landscapes is important, providing insight into the kinetics and thermodynamics of a system, as well the range of structures a system can adopt. It is, however, highly nontrivial, with the number of dimensions required for a faithful reproduction of the landscape far higher than can be represented in two or three dimensions. Metric disconnectivity graphs provide a possible solution, incorporating the landscape connectivity information present in disconnectivity graphs with structural information in the form of a metric. In this study, we present a new software package, PyConnect, which is capable of producing both disconnectivity graphs and metric disconnectivity graphs in two or three dimensions. We present as a test case the analysis of the 69‐bead BLN coarse‐grained model protein and show that, by choosing appropriate order parameters, metric disconnectivity graphs can resolve correlations between structural features on the energy landscape with the landscapes energetic and kinetic properties. © 2014 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
Application of process analytical technology for downstream purification of biotherapeutics
Authors: Rathore Anurag S. , Kapoor Gautam
Published: May 2014

The concept of Process Analytical Technology (PAT) introduced by the US FDA has received a lot of attention lately. The use of such a scheme ensures robust process performance over the entire life cycle of the product and consistent product quality at the end of the manufacturing process. Successful implementation of PAT requires use of high resolution, orthogonal analytical tools that are able to measure the critical quality attributes (CQA) of the raw materials and in‐process materials with the aim of ensuring final product quality. This article presents a review of PAT applications for monitoring commonly used downstream biotech unit operations. Focus of the review will be on recent advancements (last 5 years). Analytical tools that have been used in these approaches have also been discussed with reference to their speed of analysis, robustness and sensitivity. Also discussed is their potential to replace the traditional high performance liquid chromatography (HPLC) which continues to be the gold standard for analysis of biotech therapeutics. © 2014 Society of Chemical Industry
Suspected coronary ostium calcification identified as a protruding stent by epiaortic echography
Authors: Kim Jun Hyun , Kim Kyung Woo , Choe Won Joo
Published: May 2014

A 76‐year‐old male patient was admitted for mitral valvuloplasty. He had suffered a myocardial infarction 7 months earlier, and two stents had been inserted in the left main coronary artery and left circumflex artery. Intraoperative transesophageal echocardiography revealed a 10 × 8 mm echogenic mass at the ostium of the left main coronary artery. We initially suspected severe atheromatous calcification at the coronary ostium, which might require aortotomy and removal, but we decided to perform an epiaortic ultrasonographic scan first to obtain better images and reevaluate. Epiaortic scanning with a linear sonographic probe identified the mass as a protruding coronary stent. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound, 43:135–137, 2015