bluuebunny/crossref_metadata_2025 huggingface dataset:
Segregation of face sensitive areas within the fusiform gyrus using global signal regression? A study on amygdala resting‐state functional connectivity
Authors: Kruschwitz Johann D. , Meyer‐Lindenberg Andreas , Veer Ilya M. , Wackerhagen Carolin , Erk Susanne , Mohnke Sebastian , Pöhland Lydia , Haddad Leila , Grimm Oliver , Tost Heike , Romanczuk‐Seiferth Nina , Heinz Andreas , Walter Martin , Walter Henrik
Published: July 2015

The application of global signal regression (GSR) to resting‐state functional magnetic resonance imaging data and its usefulness is a widely discussed topic. In this article, we report an observation of segregated distribution of amygdala resting‐state functional connectivity (rs‐FC) within the fusiform gyrus (FFG) as an effect of GSR in a multi‐center‐sample of 276 healthy subjects. Specifically, we observed that amygdala rs‐FC was distributed within the FFG as distinct anterior versus posterior clusters delineated by positive versus negative rs‐FC polarity when GSR was performed. To characterize this effect in more detail, post hoc analyses revealed the following: first, direct overlays of task‐functional magnetic resonance imaging derived face sensitive areas and clusters of positive versus negative amygdala rs‐FC showed that the positive amygdala rs‐FC cluster corresponded best with the fusiform face area, whereas the occipital face area corresponded to the negative amygdala rs‐FC cluster. Second, as expected from a hierarchical face perception model, these amygdala rs‐FC defined clusters showed differential rs‐FC with other regions of the visual stream. Third, dynamic connectivity analyses revealed that these amygdala rs‐FC defined clusters also differed in their rs‐FC variance across time to the amygdala. Furthermore, subsample analyses of three independent research sites confirmed reliability of the effect of GSR, as revealed by similar patterns of distinct amygdala rs‐FC polarity within the FFG. In this article, we discuss the potential of GSR to segregate face sensitive areas within the FFG and furthermore discuss how our results may relate to the functional organization of the face‐perception circuit. Hum Brain Mapp 36:4089–4103, 2015. © 2015 Wiley Periodicals, Inc.
Validation of tractography: Comparison with manganese tracing
Authors: Knösche Thomas R. , Anwander Alfred , Liptrot Matthew , Dyrby Tim B.
Published: July 2015

In this study, we used invasive tracing to evaluate white matter tractography methods based on ex vivo diffusion‐weighted magnetic resonance imaging (dwMRI) data. A representative selection of tractography methods were compared to manganese tracing on a voxel‐wise basis, and a more qualitative assessment examined whether, and to what extent, certain fiber tracts and gray matter targets were reached. While the voxel‐wise agreement was very limited, qualitative assessment revealed that tractography is capable of finding the major fiber tracts, although there were some differences between the methods. However, false positive connections were very common and, in particular, we discovered that it is not possible to achieve high sensitivity (i.e., few false negatives) and high specificity (i.e., few false positives) at the same time. Closer inspection of the results led to the conclusion that these problems mainly originate from regions with complex fiber arrangements or high curvature and are not easily resolved by sophisticated local models alone. Instead, the crucial challenge in making tractography a truly useful and reliable tool in brain research and neurology lies in the acquisition of better data. In particular, the increase of spatial resolution, under preservation of the signal‐to‐noise‐ratio, is key. Hum Brain Mapp 36:4116–4134, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Neural correlates of self‐injurious behavior in Prader–Willi syndrome
Authors: Klabunde Megan , Saggar Manish , Hustyi Kristin M. , Hammond Jennifer L. , Reiss Allan L. , Hall Scott S.
Published: July 2015

Individuals with Prader–Willi syndrome (PWS), a genetic disorder caused by mutations to the q11‐13 region on chromosome 15, commonly show severe skin‐picking behaviors that can cause open wounds and sores on the body. To our knowledge, however, no studies have examined the potential neural mechanisms underlying these behaviors. Seventeen individuals with PWS, aged 6–25 years, who showed severe skin‐picking behaviors, were recruited and scanned on a 3T scanner. We used functional magnetic resonance imaging (fMRI) while episodes of skin picking were recorded on an MRI‐safe video camera. Three participants displayed skin picking continuously throughout the scan, three participants did not display skin picking, and the data for one participant evidenced significant B0 inhomogeneity that could not be corrected. The data for the remaining 10 participants (six male, four female) who displayed a sufficient number of picking and nonpicking episodes were subjected to fMRI analysis. Results showed that regions involved in interoceptive, motor, attention, and somatosensory processing were activated during episodes of skin‐picking behavior compared with nonpicking episodes. Scores obtained on the Self‐Injury Trauma scale were significantly negatively correlated with mean activation within the right insula and left precentral gyrus. These data indicate that itch and pain processes appear to underlie skin‐picking behaviors in PWS, suggesting that interoceptive disturbance may contribute to the severity and maintenance of abnormal skin‐picking behaviors in PWS. Implications for treatments are discussed. Hum Brain Mapp 36:4135–4143, 2015. © 2015 Wiley Periodicals, Inc.
Pharmacological inhibition of apical sodium‐dependent bile acid transporter changes bile composition and blocks progression of sclerosing cholangitis in multidrug resistance 2 knockout mice
Authors: Miethke Alexander G. , Zhang Wujuan , Simmons Julia , Taylor Amy E. , Shi Tiffany , Shanmukhappa Shiva Kumar , Karns Rebekah , White Shana , Jegga Anil G. , Lages Celine S. , Nkinin Stephenson , Keller Bradley T. , Setchell Kenneth D.R.
Published: July 2015

Deficiency of multidrug resistance 2 (mdr2), a canalicular phospholipid floppase, leads to excretion of low‐phospholipid “toxic” bile causing progressive cholestasis. We hypothesize that pharmacological inhibition of the ileal, apical sodium‐dependent bile acid transporter (ASBT), blocks progression of sclerosing cholangitis in mdr2–/– mice. Thirty‐day‐old, female mdr2–/– mice were fed high‐fat chow containing 0.006% SC‐435, a minimally absorbed, potent inhibitor of ASBT, providing, on average, 11 mg/kg/day of compound. Bile acids (BAs) and phospholipids were measured by mass spectrometry.

Compared with untreated mdr2–/– mice, SC‐435 treatment for 14 days increased fecal BA excretion by 8‐fold, lowered total BA concentration in liver by 65%, reduced total BA and individual hydrophobic BA concentrations in serum by >98%, and decreased plasma alanine aminotransferase, total bilirubin, and serum alkaline phosphatase levels by 86%, 93%, and 55%, respectively. Liver histology of sclerosing cholangitis improved, and extent of fibrosis decreased concomitant with reduction of hepatic profibrogenic gene expression. Biliary BA concentrations significantly decreased and phospholipids remained low and unchanged with treatment. The phosphatidylcholine (PC)/BA ratio in treated mice corrected toward a ratio of 0.28 found in wild‐type mice, indicating decreased bile toxicity. Hepatic RNA sequencing studies revealed up‐regulation of putative anti‐inflammatory and antifibrogenic genes, including Ppara and Igf1, and down‐regulation of several proinflammatory genes, including Ccl2 and Lcn2, implicated in leukocyte recruitment. Flow cytometric analysis revealed significant reduction of frequencies of hepatic CD11b+F4/80+ Kupffer cells and CD11b+Gr1+ neutrophils, accompanied by expansion of anti‐inflammatory Ly6C– monocytes in treated mdr2–/– mice. Conclusion: Inhibition of ASBT reduces BA pool size and retention of hydrophobic BA, favorably alters the biliary PC/BA ratio, profoundly changes the hepatic transcriptome, attenuates recruitment of leukocytes, and abrogates progression of murine sclerosing cholangitis. (Hepatology 2016;63:512–523)
Identification of a mitochondrial defect gene signature reveals NUPR1 as a key regulator of liver cancer progression
Authors: Lee Young‐Kyoung , Jee Byul A. , Kwon So Mee , Yoon Young‐Sil , Xu Wei Guang , Wang Hee‐Jung , Wang Xin Wei , Thorgeirsson Snorri S. , Lee Jae‐Seon , Woo Hyun Goo , Yoon Gyesoon
Published: July 2015

Many cancer cells require more glycolytic adenosine triphosphate production due to a mitochondrial respiratory defect. However, the roles of mitochondrial defects in cancer development and progression remain unclear. To address the role of transcriptomic regulation by mitochondrial defects in liver cancer cells, we performed gene expression profiling for three different cell models of mitochondrial defects: cells with chemical respiratory inhibition (rotenone, thenoyltrifluoroacetone, antimycin A, and oligomycin), cells with mitochondrial DNA depletion (Rho0), and liver cancer cells harboring mitochondrial defects (SNU354 and SNU423). By comparing gene expression in the three models, we identified 10 common mitochondrial defect–related genes that may be responsible for retrograde signaling from cancer cell mitochondria to the intracellular transcriptome. The concomitant expression of the 10 common mitochondrial defect genes is significantly associated with poor prognostic outcomes in liver cancers, suggesting their functional and clinical relevance. Among the common mitochondrial defect genes, we found that nuclear protein 1 (NUPR1) is one of the key transcription regulators. Knockdown of NUPR1 suppressed liver cancer cell invasion, which was mediated in a Ca2+ signaling–dependent manner. In addition, by performing an NUPR1‐centric network analysis and promoter binding assay, granulin was identified as a key downstream effector of NUPR1. We also report association of the NUPR1–granulin pathway with mitochondrial defect–derived glycolytic activation in human liver cancer. Conclusion: Mitochondrial respiratory defects and subsequent retrograde signaling, particularly the NUPR1–granulin pathway, play pivotal roles in liver cancer progression. (Hepatology 2015;62:1174‐1189)
Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study
Authors: Koehler Edith M. , Plompen Elisabeth P.C. , Schouten Jeoffrey N.L. , Hansen Bettina E. , Darwish Murad Sarwa , Taimr Pavel , Leebeek Frank W.G. , Hofman Albert , Stricker Bruno H. , Castera Laurent , Janssen Harry L.A.
Published: July 2015

Given that little is known about the prevalence of, and factors associated with, liver fibrosis in the general population, we aimed to investigate this in a large, well‐characterized cohort by means of transient elastography (TE). This study was part of the Rotterdam Study, a population‐based study among individuals ≥45 years. All participants underwent abdominal ultrasound and TE. Liver stiffness measurement (LSM) ≥8.0 kilopascals (kPa) was used as a cutoff suggesting clinically relevant fibrosis. Of 3,041 participants (age, 66.0 ± 7.6 years) with reliable LSM, 169 (5.6%) participants had LSM ≥8.0 kPa. Age (odds ratio [OR]: 2.40; 95% confidence interval [CI]: 1.72‐3.36; P < 0.001), alanine aminotransferase (ALT; OR, 1.24; 95% CI: 1.12‐1.38; P < 0.001), smoking (OR, 1.77; 95% CI: 1.16‐2.70; P = 0.008), spleen size (OR, 1.23; 95% CI: 1.09‐1.40; P = 0.001), hepatitis B surface antigen, or anti–hepatitis C virus positivity (OR, 5.38; 95% CI: 1.60‐18.0; P = 0.006), and combined presence of diabetes mellitus (DM) and steatosis (OR, 5.20; 95% CI: 3.01‐8.98; P < 0.001 for combined presence) were associated with LSM ≥8.0 kPa in multivariable analyses. The adjusted predicted probability of LSM ≥8.0 kPa increased per age decade, with probabilities ranging from 1.4% (0.9‐3.6) in participants ages 50‐60 years to 9.9% (6.8‐14.5) in participants >80 years. Participants with both DM and steatosis had the highest probabilities of LSM ≥8.0 kPa (overall probability: 17.2% [12.5‐23.4]; this probability did not increase with age [P = 0.8]). Conclusion: In this large population‐based study of older adults, LSM ≥8.0 kPa, suggestive of clinically relevant fibrosis, was present in 5.6% and was strongly associated with steatosis and DM. In the context of an aging population and an increased prevalence of DM and obesity, this study illustrates that liver fibrosis may become a more prominent public health issue in the near future. (Hepatology 2016;63:138–147)
NUMB phosphorylation destabilizes p53 and promotes self‐renewal of tumor‐initiating cells by a NANOG‐dependent mechanism in liver cancer
Authors: Siddique Hifzur R. , Feldman Douglas E. , Chen Chia‐Lin , Punj Vasu , Tokumitsu Hiroshi , Machida Keigo
Published: July 2015

Stem cell populations are maintained through self‐renewing divisions in which one daughter cell commits to a particular fate whereas the other retains the multipotent characteristics of its parent. The NUMB, a tumor suppressor, in conjunction with another tumor‐suppressor protein, p53, preserves this property and acts as a barrier against deregulated expansion of tumor‐associated stem cells. In this context, NUMB‐p53 interaction plays a crucial role to maintain the proper homeostasis of both stem cells, as well as differentiated cells. Because the molecular mechanism governing the assembly and stability of the NUMB‐p53 interaction/complex are poorly understood, we tried to identify the molecule(s) that govern this process. Using cancer cell lines, tumor‐initiating cells (TICs) of liver, the mouse model, and clinical samples, we identified that phosphorylations of NUMB destabilize p53 and promote self‐renewal of TICs in a pluripotency‐associated transcription factor NANOG‐dependent manner. NANOG phosphorylates NUMB by atypical protein kinase C zeta (aPKCζ), through the direct induction of Aurora A kinase (AURKA) and the repression of an aPKCζ inhibitor, lethal (2) giant larvae. By radioactivity‐based kinase activity assays, we showed that NANOG enhances kinase activities of both AURKA and aPKCζ, an important upstream process for NUMB phosphorylation. Phosphorylation of NUMB by aPKCζ destabilizes the NUMB‐p53 interaction and p53 proteolysis and deregulates self‐renewal in TICs. Conclusion: Post‐translational modification of NUMB by the NANOG‐AURKA‐aPKCζ pathway is an important event in TIC self‐renewal and tumorigenesis. Hence, the NANOG‐NUMB‐p53 signaling axis is an important regulatory pathway for TIC events in TIC self‐renewal and liver tumorigenesis, suggesting a therapeutic strategy by targeting NUMB phosphorylation. Further in‐depth in vivo and clinical studies are warranted to verify this suggestion. (Hepatology 2015;62:1466‐1479)
Direct Arylation of 5‐Iodouracil and 5‐Iodouridine with Heteroarenes and Benzene via Photochemical Reaction
Authors: Yang Qian , Wei Tao , He Yun , Liang Yong , Zhang Zun‐Ting
Published: July 2015

A method for the direct arylation of 5‐iodouracil and 5‐iodouridine was found to proceed in moderate yields. By irradiating mixtures of 5‐iodouracil or 5‐iodouridine and a series of five‐membered heterocycles such as 1H‐pyrrole, furan, 2‐methylfuran, 1‐methyl‐1H‐pyrrole, thiophene, as well as benzene in MeCN/H2O with a Hg lamp, 5‐aryluracils and 5‐aryluridines were synthesized. The reaction proceeded smoothly without the requirement of adding any transition metals or ligands.
An Efficient and Chemoselective Knoevenagel/Hemiketalization Process for the Synthesis of New 2H‐Chromenes in a One‐Pot Three‐Component Reaction
Authors: Rao Lenka Chandrasekhara , Kumar Nandigama Satish , Meshram Harshadas Mitaram
Published: July 2015

A novel L‐proline‐catalyzed mild and ecological approach towards the synthesis of 2H‐chromene derivatives was achieved by Knoevenagel reaction followed by an intramolecular hemiketalization process. In the present protocol, chemoselectivity has been successfully achieved by using L‐proline as catalyst. This eco‐friendly and chemoselective reaction provided an alternative synthetic method to prepare previously unknown 2H‐chromene derivatives in a one‐pot reaction.
Computational Studies on Intramolecular Cycloadditions of Azidoenynes and Azidobutenenitriles to Give 6H‐Pyrrolo[1,2‐c][1,2,3]triazoles and 5H‐Pyrrolo[1,2‐d]tetrazoles
Authors: Audran Gérard , Brémond Paul , El Abed Douniazad , Marque Sylvain R. A. , Siri Didier , Santelli Maurice
Published: July 2015

Energetics of intramolecular cycloadditions of azidoenynes and azidobutenenitriles to give 6H‐pyrrolo[1,2‐c][1,2,3]triazoles and 5H‐pyrrolo[1,2‐d]tetrazoles have been calculated at the B3LYP/6.311++G(3df,3pd) level of theory in ideal gas and in H2O as solvent. Stabilities of the corresponding anions, tautomers, and isomers are discussed. Transition states of the cyclization of parent compounds are determined at the same level of theory.
The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B‐cell lymphoma patients
Authors: Okamoto Akinao , Yanada Masamitsu , Inaguma Yoko , Tokuda Masutaka , Morishima Satoko , Kanie Tadaharu , Yamamoto Yukiya , Mizuta Shuichi , Akatsuka Yoshiki , Yoshikawa Tetsushi , Mizoguchi Yoshikazu , Nakamura Shigeo , Okamoto Masataka , Emi Nobuhiko
Published: July 2015

Epstein–Barr virus (EBV)‐encoded small RNA in situ hybridization (EBER‐ISH) is a widely accepted method to evaluate EBV involvement in diffuse large B‐cell lymphoma (DLBCL), although little is known regarding associations between EBV DNA load and the EBER status and whether EBV DNA load data provide additional clinical information. In this study, we quantified EBV DNA load in diagnostic specimens from DLBCL patients diagnosed at our hospital to evaluate clinical implications of EBV DNA load in diagnostic specimens as contrasted with EBER‐ISH. Among 140 DLBCL patients without underlying immunodeficiency, 51 were evaluable for both EBER and EBV DNA load, 83 for EBER only and one for EBV DNA load only. The median EBV DNA load was 708 copies/µg. Although EBV DNA load was significantly higher for EBER‐positive patients than for EBER‐negative patients (p < 0.001), EBV DNA was detected in up to 72% of EBER‐negative patients. Progression‐free survival and overall survival were significantly worse for patients with EBV DNA load above 700 copies/µg than for those with EBV DNA load below 700 copies/µg (p = 0.009 and p = 0.003); they were also significantly worse for EBER‐positive patients than for EBER‐negative patients (p < 0.001 and p = 0.001). Even among EBER‐negative patients, higher EBV DNA load conferred worse progression‐free survival and overall survival (p = 0.041 and p = 0.013). These findings indicate that EBV DNA load in diagnostic specimens is not a simple surrogate for the EBER status and may be a potential biomarker associated with EBV involvement and prognosis in DLBCL. Copyright © 2015 John Wiley & Sons, Ltd.
Obstacles to long‐term soil moisture monitoring with heated distributed temperature sensing
Authors: Sourbeer John J. , Loheide Steven P.
Published: July 2015

The field deployment of a heated distributed temperature sensor (DTS) for over three years has revealed two obstacles to estimating soil moisture (θ) that may hamper subsurface DTS applications as well as use of other subsurface thermal probes. The first observed obstacle was a hysteretic response of the DTS sensor. The relationship between θ and the temperature response (∆T) within the cable was not only dependent on θ of the soil, but also on the previous wetting and drying cycles leading to that state. The second observed obstacle was soil structure healing. Soil structure healing causes the relationship between ∆T and θ to evolve through time; this calibration curve becomes flatter, or less sensitive, as the surrounding soil makes better contact with the cable. Effects of the hysteretic response of the instrument and soil structure healing are largely the result of small gaps between the cable and soil. These small gaps can be approximated by a contact resistance between the cable and soil. In this article we characterize the occurrence of hysteretic and soil structure healing effects from field data and parameterize contact resistance by simulating heat transfer using a numerical modelling approach Copyright © 2015 John Wiley & Sons, Ltd.
Development of a total dissolved solids (TDS) chronic effects benchmark for a northern Canadian lake
Authors: Chapman Peter M , McPherson Cathy A
Published: July 2015

Laboratory chronic toxicity tests with plankton, benthos, and fish early life stages were conducted with total dissolved solids (TDS) at an ionic composition specific to Snap Lake (Northwest Territories, Canada), which receives treated effluent from the Snap Lake Diamond Mine. Snap Lake TDS composition has remained consistent from 2007 to 2014 and is expected to remain unchanged through the life of the mine: Cl (45%–47%), Ca (20%–21%), Na (10%–11%), sulfate (9%); carbonate (5%–7%), nitrate (4%), Mg (2%–3%), and minor contributions from K and fluoride. The TDS concentrations that resulted in negligible effects (i.e., 10% or 20% effect concentrations) to taxa representative of resident biota ranged from greater than 1100 to greater than 2200 mg/L, with the exception of a 21% effect concentration of 990 mg/L for 1 of 2 early life stage fish dry fertilization tests (wet fertilization results were >1480 mg/L). A conservative, site-specific, chronic effects benchmark for Snap Lake TDS of 1000 mg/L was derived, below the lowest negligible effect concentration for the most sensitive resident taxon tested, the cladoceran, Daphnia magna (>1100 mg/L). Cladocerans typically only constitute a few percent of the zooplankton community and biomass in Snap Lake; other plankton effect concentrations ranged from greater than 1330 to greater than 1510 mg/L. Chironomids, representative of the lake benthos, were not affected by greater than 1380 mg/L TDS. Early life stage tests with 3 fish species resulted in 10% to 20% effect concentrations ranging from greater than 1410 to greater than 2200 mg/L. The testing undertaken is generally applicable to northern freshwaters, and the concept can readily be adapted to other freshwaters either for TDS where ionic composition does not change or for major ionic components, where TDS composition does change. Integr Environ Assess Manag 2016;12:371–379. © 2015 SETAC

Key Points

Total dissolved solids from mining increasing in a northern Canadian lake. Novel site-specific toxicity testing conducted to determine a protective chronic effects benchmark. Resident taxa tested representing all components of the food chain (benthos, plankton, fish). Chronic effects benchmark of 1,000 mg/L will protect lake function while allowing mining to continue.
The Groucho/Transducin‐like enhancer of split protein family in animal development
Authors: Agarwal Megha , Kumar Pankaj , Mathew Sam J.
Published: July 2015

Corepressors are proteins that cannot bind DNA directly but repress transcription by interacting with partner proteins. The Groucho/Transducin‐Like Enhancer of Split (TLE) are a conserved family of corepressor proteins present in animals ranging from invertebrates such as Drosophila to vertebrates such as mice and humans. Groucho/TLE proteins perform important functions throughout the life span of animals, interacting with several pathways and regulating fundamental processes such as metabolism. However, these proteins have especially crucial functions in animal development, where they are required in multiple tissues in a temporally regulated manner. In this review, we summarize the functions of the Groucho/TLE proteins during animal development, emphasizing on specific tissues where they play essential roles. © 2015 IUBMB Life, 67(7):472–481, 2015
Deubiquitinating enzymes in cellular signaling and disease regulation
Authors: Hanpude Pranita , Bhattacharya Sushmita , Dey Amit Kumar , Maiti Tushar Kanti
Published: July 2015

Protein post‐translational modification by ubiquitin represents a complex signaling system that regulates many cellular events including proteostasis to intercellular communications. Deubiquitinating enzymes (DUBs) that specifically disassemble Ub‐chains or regulate ubiquitin homeostasis reside as a central component in ubiquitin signaling. Human genome encodes almost 100 DUBs and majority of them are not well characterized. Considerable progress has been made in the understanding of enzymatic mechanism; however, their cellular substrate specificity and regulation are largely unknown. Involvement of DUBs in disease regulation has been depicted since its discovery and several attempts have been made for evaluating DUBs as a drug target. In this review, we have updated briefly a new insight of DUBs activity, their cellular role, disease regulation, and therapeutic potential. © 2015 IUBMB Life, 67(7):544–555, 2015
New insights into T cells and their signature cytokines in atopic dermatitis
Authors: Wang Ao‐xue , Xu Landén Ning
Published: July 2015

An imbalance of the adaptive immune system mediated by various T cells plays a pivotal role in the pathogenesis of atopic dermatitis (AD). Traditionally, sustained exposure of pathogens tailors immune responses and drives the development of specialized T helper (Th) 2‐bias cytokine environment. The increasing understanding of T cell biology has refreshed the roles of classical Th2 responses and regulatory T cells in the development of AD. In particular, the identification of novel CD4+ T cell subsets such as Th9, Th17, and Th22 cells provide further interpretation of immunological mechanisms underlying AD. In this report, we reviewed the functional roles of CD4+ T cell subsets and their derived signature cytokines in AD. We focused on important discoveries of the contribution of CD4+ T cell cytokines to immunomodulation in AD, and particularly, highlighted the multiple consequences of immune dysregulation on the barrier defect of the skin. We subsequently discussed the flexibility and plasticity of these T cells in vivo in terms of cytokine production. T cells involved in innate immunity were also mentioned. Taking the pivotal and varied roles of T‐cell subpopulations and the functional cytokine milieus into account, T cell targeting therapy may thus open up new opportunities for mechanism‐based therapeutic intervention. © 2015 IUBMB Life, 67(8):601–610, 2015
Parenting and Video Games
Authors: Steinkuehler Constance
Published: July 2015

There is a terrific disconnect between parenting advice related to media and the realities of contemporary parenting. We condone enrichment parenting and condemn the use of “digital babysitters,” admonishing parents who exceed the two‐hour screen time limitation even when, all the while, no one is listening. Parents are not merely blasé about their children's development and well‐being. Rather, for many parents, games and other media are a best‐fit solution to the problem of resource constraints. Time is the resource; the demands on real‐life parents and families are the constraint. Thus, we digital media literacy scholars would do well to shift our focus from children in relative isolation to families as a system. Only then will be we begin to see the historical, economic, and material (still highly gendered) contexts that shape child rearing and media use.
Composing in Public
Authors: Hall Matthew
Published: July 2015

Although scholars have investigated the ways youths individually enact composing practices and the impact of audience on these practices, this study examines the impact of an audience physically present while composing in a shared, public space—an ambient audience. Blurring the line between traditional notions of audience and collaborator through a process of distributed co‐construction with individual composers, the ambient audience proved generative for the composing work of individuals. This article highlights two examples of this distributed co‐construction in action: the co‐constructed framing of everyday experiences as the topic for created videos and the shared aesthetic of juxtaposition that the youth participants co‐constructed while composing individual images. The results of this study suggest future research and development of instructional approaches that address the social nature of composing with a specific look at the ways publics influence processes of composing.
Data analysis of response interruption and redirection as a treatment for vocal stereotypy
Authors: Wunderlich Kara L. , Vollmer Timothy R.
Published: July 2015

Vocal stereotypy, or repetitive, noncontextual vocalizations, is a problematic form of behavior exhibited by many individuals with autism spectrum disorder (ASD). Recent research has evaluated the efficacy of response interruption and redirection (RIRD) in the reduction of vocal stereotypy. Research has indicated that RIRD often results in reductions in the level of vocal stereotypy; however, many previous studies have only presented data on vocal stereotypy that occurred outside RIRD implementation. The current study replicated the procedures of previous studies that have evaluated the efficacy of RIRD and compared 2 data‐presentation methods: inclusion of only data collected outside RIRD implementation and inclusion of all vocal stereotypy data from the entirety of each session. Subjects were 7 children who had been diagnosed with ASD. Results indicated that RIRD appeared to be effective when we evaluated the level of vocal stereotypy outside RIRD implementation, but either no reductions or more modest reductions in the level of vocal stereotypy during the entirety of sessions were obtained for all subjects. Results suggest that data‐analysis methods used in previous research may overestimate the efficacy of RIRD.
The potential health challenges of TiO2 nanomaterials
Authors: Sha Baoyong , Gao Wei , Cui Xingye , Wang Lin , Xu Feng
Published: July 2015

Titanium dioxide (TiO2) nanomaterials (NMs) have found widespread applications owing to their attractive physical and chemical properties. As a result, the potential adverse impacts of nano‐TiO2 exposure on humans have become a matter of concern. This review presents the state‐of‐the‐art advances on the investigations of the adverse effects of NMs, including the potential exposure routes of nano‐TiO2 (e.g. respiratory system, skin absorption and digestive system), the physico‐chemical characterizations of nano‐TiO2 (e.g. crystal structure, shape,size, zeta potential, treatment media, aggregation and agglomeration tendency, surface characteristics and coatings), risk evaluation of nanotoxicity (e.g. cytotoxicity, ecotoxicity, phototoxicity, and phytotoxicity) and potential mechanisms of adverse effects (e.g. generation of reactive oxygen species, oxidative stress and organelle dysfunction). The review aims to facilitate scientific assessments of health risks to nano‐TiO2, which would guide the safe applications of NMs in our daily life. Copyright © 2015 John Wiley & Sons, Ltd.
The applications of conductive nanomaterials in the biomedical field
Authors: Li Xiaoming , Zhao Tianxiao , Sun Lianwen , Aifantis Katerina E. , Fan Yubo , Feng Qingling , Cui Fuzhai , Watari Fumio
Published: July 2015

As their name suggests, conductive nanomaterials (CNMs) are a type of functional materials, which not only have a high surface area to volume ratio, but also possess excellent conductivity. Thus far, CNMs have been widely used in biomedical applications, such as effectively transferring electrical signals, and providing a large surface area to adsorb proteins and induce cellular functions. Recent works propose further applications of CNMs in biosensors, tissue engineering, neural probes, and drug delivery. This review focuses on common types of CNMs and elaborates on their unique properties, which indicate that such CNMs have a potential to develop into a class of indispensable biomaterials for the diagnosis and therapy of human diseases. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 322–339, 2016.
Degree of Trauma Differs for Major Osteoporotic Fracture Events in Older Men Versus Older Women
Authors: Ensrud Kristine E , Blackwell Terri L , Cawthon Peggy M , Bauer Douglas C , Fink Howard A , Schousboe John T , Black Dennis M , Orwoll Eric S , Kado Deborah M , Cauley Jane A , Mackey Dawn C ,   for the Osteoporotic Fractures in Men (MrOS) Study of Osteoporotic Fractures (SOF) Research Groups
Published: July 2015

To examine the degree of trauma in major osteoporotic fractures (MOF) in men versus women, we used data from 15,698 adults aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study (5994 men) and the Study of Osteoporotic Fractures (SOF) (9704 women). Participants were contacted tri-annually to ascertain incident fractures, which were confirmed by radiographic reports and coded according to degree of self-reported trauma. Trauma was classified as low (fall from ≤ standing height; fall on stairs, steps, or curb; minimal trauma other than fall [coughing, turning over]); moderate (collisions with objects during normal activity without associated fall); or high (fall from > standing height; severe trauma [motor vehicle accident, assault]). MOF included hip, clinical vertebral, wrist, and humerus fractures. Mean fracture follow-up was 9.1 years in SOF and 8.7 years in MrOS. A total of 14.6% of the MOF in men versus 6.3% of the MOF in women were classified as high trauma (p < 0.001); men versus women more often experienced fractures resulting from severe trauma as well as from fall > standing height. High-trauma fractures were more significantly common in men versus women at the hip (p = 0.002) and wrist (p < 0.001) but not at the spine or humerus. Among participants with MOF, the odds ratio of a fracture related to high-trauma fracture among men versus women was 3.12 (95% confidence interval [CI] 1.70–5.71) after adjustment for traditional risk factors. Findings were similar in analyses limited to participants with hip fractures (odds ratio [OR] = 3.34, 95% CI 1.04–10.67) and those with wrist fracture (OR = 5.68, 95% CI 2.03–15.85). Among community-dwelling older adults, MOF are more likely to be related to high trauma in men than in women. These findings are not explained by sex differences in conventional risk factors and may reflect a greater propensity among men to engage in risky behavior. © 2015 American Society for Bone and Mineral Research.
NF-κB Has a Direct Role in Inhibiting Bmp- and Wnt-Induced Matrix Protein Expression
Authors: Tarapore Rohinton S , Lim Jason , Tian Chen , Pacios Sandra , Xiao Wenmei , Reid Daniel , Guan Hancheng , Mattos Marcelo , Yu Bo , Wang Cun-Yu , Graves Dana T
Published: July 2015

The host response to pathogens through nuclear factor κB (NF-κB) is an essential defense mechanism for eukaryotic organisms. NF-κB-mediated host responses inhibit bone and other connective tissue synthesis and are thought to affect the transcription of matrix proteins through multiple indirect pathways. We demonstrate that inhibiting NF-κB in osteoblasts increases osteocalcin expression in vivo in mice with periodontal disease. Mutating NF-κB binding sites on osteocalcin (OC) or bone sialoprotein (Bsp) promoters rescues the negative impact of NF-κB on their transcription and that NF-κB can inhibit Wnt- and Bmp-induced OC and Bsp transcription, even when protein synthesis is inhibited, indicating a direct effect of NF-κB. This inhibition depends on p65-p50 NF-κB heterodimer formation and deacetylation by HDAC1 but is not affected by the noncanonical NF-κB pathway. Moreover, NF-κB reduces Runx2 and β-catenin binding to OC/Bsp promoters independently of their nuclear localization. Thus, inflammatory signals stimulate the direct interaction of NF-κB with response elements to inhibit binding of β-catenin and Runx2 binding to nearby consensus sites and reduce expression of matrix proteins. This direct mechanism provides a new explanation for the rapid decrease in new bone formation after inflammation-related NF-κB activation. © 2015 American Society for Bone and Mineral Research.
INTRODUCING THRIVING AT WORK TO THE FIELD OF COMMUNITY PSYCHOLOGY
Authors: Boyd Neil M.
Published: July 2015

Advances in the organizational behavior and management literatures toward social sustainability are leading to new theories, models, and concepts that promote employee well‐being and functioning while helping organizations achieved desired ends. One concept that has yet to be imported to community psychology is thriving at work, which is the joint experience of learning and vitality, where a worker is able to grow, develop, and feel energized (Spreitzer et al., 2005). This paper will articulate a definition of thriving at work, explore current theory and modeling of the concept, and show why it is a unique concept of importance to community psychologists. Then, thriving at work will be integrated into recent scholarship on sense of community and sense of community responsibility in organizational settings (Boyd & Nowell, 2014; Nowell & Boyd, 2010; 2011), with an eye on showing how thriving at work can help community psychologists advance organizational behavior research in our field. Finally, in the epilogue of the paper, some thoughts will be advanced on how thriving at work can be incorporated with important research topics in the field of community psychology, and how it can potentially be translated to community contexts in general.
INTEGRATING ORGANIZATION STUDIES AND COMMUNITY PSYCHOLOGY: A PROCESS MODEL OF AN ORGANIZING SENSE OF PLACE IN WORKING LIVES
Authors: Calvard Thomas S.
Published: July 2015

In this conceptual paper, I propose to advance thinking about organization theory in community contexts by theorizing about the roles of place and space in working lives. I argue that work in the mainstream of organization studies often downplays contextual aspects of the community‐based places that workers inhabit, largely by trying to generalize across them. A colourless language of firms, institutions, and agents can obscure more humanistic, ecological understandings of how workers occupy and make use of various places for supporting their well‐being and sense of self. A sense of place (and by implication, space) has the potential to draw together relevant existing work at the organization studies‐community psychology interface more comprehensively. I therefore integrate key ideas from this interface with sensemaking theory and present a three‐stage process model of an organizing sense of place. I conclude by discussing the implications arising for future research, theorizing, and practice.
THE IMPACT OF EVERYDAY EXPERIENCES ON PLANNED ORGANIZATIONAL CHANGE: APPLYING SCHEMATIC CHANGE THEORY TO THE STUDY OF NARRATIVES IN COMMUNITY‐BASED ORGANIZATIONS
Authors: Bess Kimberly D.
Published: July 2015

This case study examines change experiences of two community‐based organizations participating in a planned organizational change (POC) project. Research on POC in community psychology has emphasized teleological change processes (e.g., strategic planning). This paper aims to broaden the discourse through a qualitative study focused on the role of cognition and sensemaking in organizational change. A schematic change process model is proposed and used to explore how members' narratives related to everyday change shape the way they make sense of and engage in a formalized, change process. Analysis revealed two types of change narratives: romantic and tragic. The findings suggest that romantic narratives reinforce existing paradigms of practice, but can also serve as positive resources for members during POC. In contrast, tragic narratives may serve as an impetus for POC, however, when related to negative internal organizational dynamics can undermine and impede the POC process. Implications for change readiness are discussed.
PERSONAL BENEFITS OF STRONG ORGANIZATIONAL AND COMMUNITY TIES: HEALTH, ENGAGEMENT AND RETENTION
Authors: Sinclair Robert R. , Cheung Janelle H. , Arpin Sarah N. , Mohr Cynthia P.
Published: July 2015

This study extended past research on organizational commitment by proposing a new construct of community commitment. The authors drew from past organizational research to theorize distinct effects of affective and continuance community commitment in relation to nurses' health, retention, and engagement. These effects were investigated in a prospective study in which nurses' (N = 330) organizational and community commitment were assessed at one time point and measures of health, retention, and engagement were captured nine months later. Affective community commitment predicted health and retention outcomes after controlling for both types of organizational commitment, but continuance commitment did not. Mediation analyses suggested that continuance community commitment had indirect effects on outcomes through its relationship with continuance organizational commitment. Neither form of community commitment was associated with professional or organizational turnover intentions. We discuss the implications of these findings for future research in both community and organizational psychology.
Distinct Roles for Intestinal Epithelial Cell‐Specific Hdac1 and Hdac2 in the Regulation of Murine Intestinal Homeostasis
Authors: Gonneaud Alexis , Turgeon Naomie , Boudreau François , Perreault Nathalie , Rivard Nathalie , Asselin Claude
Published: July 2015

The intestinal epithelium responds to and transmits signals from the microbiota and the mucosal immune system to insure intestinal homeostasis. These interactions are in part conveyed by epigenetic modifications, which respond to environmental changes. Protein acetylation is an epigenetic signal regulated by histone deacetylases, including Hdac1 and Hdac2. We have previously shown that villin‐Cre‐inducible intestinal epithelial cell (IEC)‐specific Hdac1 and Hdac2 deletions disturb intestinal homeostasis. To determine the role of Hdac1 and Hdac2 in the regulation of IEC function and the establishment of the dual knockout phenotype, we have generated villin‐Cre murine models expressing one Hdac1 allele without Hdac2, or one Hdac2 allele without Hdac1. We have also investigated the effect of short‐term deletion of both genes in naphtoflavone‐inducible Ah‐Cre and tamoxifen‐inducible villin‐CreER mice. Mice with one Hdac1 allele displayed normal tissue architecture, but increased sensitivity to DSS‐induced colitis. In contrast, mice with one Hdac2 allele displayed intestinal architecture defects, increased proliferation, decreased goblet cell numbers as opposed to Paneth cells, increased immune cell infiltration associated with fibrosis, and increased sensitivity to DSS‐induced colitis. In comparison to dual knockout mice, intermediary activation of Notch, mTOR, and Stat3 signaling pathways was observed. While villin‐CreER Hdac1 and Hdac2 deletions led to an impaired epithelium and differentiation defects, Ah‐Cre‐mediated deletion resulted in blunted proliferation associated with the induction of a DNA damage response. Our results suggest that IEC determination and intestinal homeostasis are highly dependent on Hdac1 and Hdac2 activity levels, and that changes in the IEC acetylome may alter the mucosal environment. J. Cell. Physiol. 231: 436–448, 2016. © 2015 Wiley Periodicals, Inc.
Genetic variation of CYP3A5 influences paclitaxel/carboplatin‐induced toxicity in Chinese epithelial ovarian cancer patients
Authors: Hu Lei , Lv Qiao‐Li , Guo Ying , Cheng Lin , Wu Na‐Yiyuan , Qin Chong‐Zhen , Zhou Hong‐Hao
Published: July 2015

Combination chemotherapy with platinum and taxane is the first‐line treatment for ovarian cancer. The dose‐limiting toxicities of these drugs include neuropathy, leukopenia, and neutropenia, but they exhibit substantial interindividual variability. This study investigated the relationship between CYP3A5 polymorphisms and paclitaxel/carboplatin‐induced toxicity in Chinese epithelial ovarian cancer patients. Seventy‐five patients with epithelial ovarian cancer were recruited. After combination chemotherapy, genotype analysis was conducted, and toxic effects were evaluated according to the Common Toxicity Criteria. A significant association was found between myelosuppression and the CYP3A5*3 genotype. CYP3A5*3/*1 patients showed a significantly higher risk of developing leukopenia (P < .001; Pearson's χ2 test) and neutropenia (P < .001; Pearson's χ2 test) than CYP3A5*3*3 patients. CYP3A5*3/*3 patients had significantly higher median leukocyte and neutrophil nadir counts than CYP3A5*3*1 patients (P < .001, Mann–Whitney U test). However, we did not observe an association between neuropathy and CYP3A5*3 in this study (P =.64; Pearson's χ2 test). This is the first study to verify the influence of CYP3A5 polymorphisms on paclitaxel/carboplatin‐induced toxicity in Chinese epithelial ovarian cancer patients. Our findings suggest that interindividual variability in paclitaxel/carboplatin‐induced myelosuppression can be predicted by CYP3A5*3 genotyping and that incorporation of CYP3A5*3 genetic data in treatment selection could help to reduce myelosuppression events, thereby individualizing paclitaxel/carboplatin pharmacotherapy.
Bromination of guaiacol and syringol using ionic liquids to obtain bromides
Authors: Sequeiros Ane , Serrano Luis , Labidi Jalel
Published: July 2015

BACKGROUND

An understanding of the bromination reaction with guaiacol and syringol allows value added products to be obtained from the lignin depolymerized oil.

RESULTS

N‐bromosuccinimide (NBS) and the ionic liquid [Bmim]Br were combined to brominate guaiacol (G) and syringol (S) at room temperature (25 °C). The first step was to bromine guaiacol and syringol separately for a better understanding of the process. The mixture of G and S was brominated with two different solvents diethyl ether (DEE) and ethyl acetate (EtAc) during the L‐L extraction to observe variations in the process and the conversion. The results were analyzed by GC‐MS and 13C NMR. The mass spectra showed the formation of isomers of p‐BrG and p‐BrS. The two solvents gave similar results. However, even though the conversions of G and S were higher with DEE (XG 67.19% and XS 71.86%) than with EtAc (XG 49.62% and XS 59.90%), EtAc (ΣXBrG 29.94% and ΣXBrS 28.29%) extracted in proportion more of the desired products than DEE (ΣXBrG 24.22% and ΣXBrS 34.86%).

CONCLUSIONS

The results of the first experiments showed the formation of isomers of p‐BrS and p‐BrG. The second results showed that EtAc was able to extract more products than DEE. In conclusion, EtAc was the better solvent for the bromination reaction with the advantage of easy handling and recyclability. © 2015 Society of Chemical Industry
Scale‐up of abatement of fermentation inhibitors from acid hydrolysates for efficient conversion to ethanol as biofuel
Authors: Gupta Rishi , Mehta Girija , Kuhad Ramesh Chander
Published: July 2015

BACKGROUND

The presence of sugar and lignin degradation products, viz. furans and phenolics, make the acid hydrolysate toxic to the microbes. This work attempts to develop an efficient method for the abatement of these microbial inhibitors at pilot scale.

RESULT

Among various methods for detoxifying fermentation inhibitors from acid hydrolysate of Prosopis juliflora, activated charcoal (2.0%) removed inhibitors almost completely, followed by ion‐exchange resins (73% phenolics and 84% furans). The neutralization and alkalinization treatments removed specifically furans and caused higher loss of sugars (∼50%), while the enzymatic treatment was more effective on removal of furans. The charcoal detoxification process on scale up (20 L), achieved the abatement of 87–93% phenolics and 87–96% furans from acid hydrolysate. The activated charcoal was regenerated and use of regenerated charcoal removed phenolics and furfurals from acid hydrolysate of P. juliflora by 83% and 86%, respectively. The detoxified hydrolysate on fermentation with Pichia stipitis NCIM 3499 produced 6.85 g L−1 ethanol with 0.35 g g−1 yield and 0.43 g L−1 h−1 productivity.

CONCLUSION

Activated charcoal adsorption was found to be the most effective and cheap method for abatement of inhibitors. Moreover, regeneration of charcoal and the scalability of the process make it industrially competitive. © 2015 Society of Chemical Industry