bluuebunny/crossref_metadata_2025 huggingface dataset:
S1P1 deletion in oligodendroglial lineage cells: Effect on differentiation and myelination
Authors: Dukala Danuta E. , Soliven Betty
Published: December 2015

Sphingosine 1‐phosphate (S1P) receptors are G protein‐coupled receptors expressed by many cell types, including cells of oligodendrocyte (OLG) lineage. We had previously shown that targeted deletion of S1P1 in OLG lineage cells did not result in obvious clinical phenotype or altered number of OLGs at 3 months, but there were subtle abnormalities in myelin. In this study, we examined the role of S1P1 in developmental myelination and cell survival, focusing on age 3 weeks. We found that S1P1 deficiency led to delayed differentiation of OLG progenitors (OPCs) into OLGs that is independent of p38 phosphorylation. This was accompanied by decreased levels of myelin basic protein (MBP) but not of myelin‐OLG glycoprotein (MOG), and slight decrease in myelin thickness in the corpus callosum of S1P1 conditional knockout (CKO) mice. S1P1‐deficient OLGs exhibited slower process extension, which was associated with attenuated phosphorylation of extracellular signal regulated kinases (ERKs) and p21‐activated kinases (PAKs), and with upregulation of tropomodulin1. Basal levels of pAkt were not affected, though expectedly, no response to a selective S1P1 agonist SEW2871 was observed. S1P1‐deficient OLGs did not exhibit increased cell death in response to cuprizone, tumor necrosis factor‐α, or deprivation of nutrients and growth factors. We conclude that S1P1 signaling regulates OLG development, morphological maturation and early myelination. GLIA 2016;64:570–582
Pyk2 is essential for astrocytes mobility following brain lesion
Authors: Giralt Albert , Coura Renata , Girault Jean‐Antoine
Published: December 2015

Proline‐rich tyrosine kinase 2 (Pyk2) is a calcium‐dependent, non‐receptor protein‐tyrosine kinase of the focal adhesion kinase (FAK) family. Pyk2 is enriched in the brain, especially the forebrain. Pyk2 is highly expressed in neurons but is also present in astrocytes, where its role is not known. We used Pyk2 knockout mice (Pyk2−/−) developed in our laboratory to investigate the function of Pyk2 in astrocytes. Morphology and basic properties of astrocytes in vivo and in culture were not altered in the absence of Pyk2. However, following stab lesions in the motor cortex, astrocytes‐mediated wound filling was slower in Pyk2−/− than in wild‐type littermates. In an in vitro wound healing model, Pyk2−/− astrocytes migrated slower than Pyk2+/+ astrocytes. The role of Pyk2 in actin dynamics was investigated by treating astrocytic cultures with the actin‐depolymerizing drug latrunculin B. Actin filaments re‐polymerization after latrunculin B treatment was delayed in Pyk2−/− astrocytes as compared with wild‐type astrocytes. We mimicked wound‐induced activation by treating astrocytes in culture with tumor‐necrosis factor alpha (TNFα), which increased Pyk2 phosphorylation at Tyr402. TNFα increased PKC activity, and Rac1 phosphorylation at Ser71 similarly in wild‐type and Pyk2‐deficient astrocytes. Conversely, we found that gelsolin, an actin‐capping protein known to interact with Pyk2 in other cell types, was less enriched at the leading edge of migrating Pyk2−/− astrocytes, suggesting that its lack of recruitment mediated in part the effects of the mutation. This work shows the critical role of Pyk2 in astrocytes migration during wound healing. GLIA 2016;64:620–634
Atypical age‐dependent effects of autism on white matter microstructure in children of 2–7 years
Authors: Ouyang Minhui , Cheng Hua , Mishra Virendra , Gong Gaolang , Mosconi Matthew W. , Sweeney John , Peng Yun , Huang Hao
Published: December 2015

Atypical age‐dependent changes of white matter (WM) microstructure play a central role in abnormal brain maturation of the children with autism spectrum disorder (ASD), but their early manifestations have not been systematically characterized. The entire brain core WM voxels were surveyed to detect differences in WM microstructural development between 31 children with ASD of 2–7 years and 19 age‐matched children with typical development (TD), using measurements of fractional anisotropy (FA) and radial diffusivity (RD) from diffusion tensor imaging (DTI). The anatomical locations, distribution, and extent of the core WM voxels with atypical age‐dependent changes in a specific tract or tract group were delineated and evaluated by integrating the skeletonized WM with a digital atlas. Exclusively, unidirectional FA increases and RD decreases in widespread WM tracts were revealed in children with ASD before 4 years, with bi‐directional changes found for children with ASD of 2–7 years. Compared to progressive development that raised FA and lowered RD during 2–7 years in the TD group, flattened curves of WM maturation were found in multiple major WM tracts of all five tract groups, particularly associational and limbic tracts, in the ASD group with trend lines of ASD and TD crossed around 4 years. We found atypical age‐dependent changes of FA and RD widely and heterogeneously distributed in WM tracts of children with ASD. The early higher WM microstructural integrity before 4 years reflects abnormal neural patterning, connectivity, and pruning that may contribute to aberrant behavioral and cognitive development in ASD. Hum Brain Mapp 37:819–832, 2016. © 2015 Wiley Periodicals, Inc.
Shared and distinct contributions of rostrolateral prefrontal cortex to analogical reasoning and episodic memory retrieval
Authors: Westphal Andrew J. , Reggente Nicco , Ito Kaori L. , Rissman Jesse
Published: December 2015

Rostrolateral prefrontal cortex (RLPFC) is widely appreciated to support higher cognitive functions, including analogical reasoning and episodic memory retrieval. However, these tasks have typically been studied in isolation, and thus it is unclear whether they involve common or distinct RLPFC mechanisms. Here, we introduce a novel functional magnetic resonance imaging (fMRI) task paradigm to compare brain activity during reasoning and memory tasks while holding bottom‐up perceptual stimulation and response demands constant. Univariate analyses on fMRI data from twenty participants identified a large swath of left lateral prefrontal cortex, including RLPFC, that showed common engagement on reasoning trials with valid analogies and memory trials with accurately retrieved source details. Despite broadly overlapping recruitment, multi‐voxel activity patterns within left RLPFC reliably differentiated these two trial types, highlighting the presence of at least partially distinct information processing modes. Functional connectivity analyses demonstrated that while left RLPFC showed consistent coupling with the fronto‐parietal control network across tasks, its coupling with other cortical areas varied in a task‐dependent manner. During the memory task, this region strengthened its connectivity with the default mode and memory retrieval networks, whereas during the reasoning task it coupled more strongly with a nearby left prefrontal region (BA 45) associated with semantic processing, as well as with a superior parietal region associated with visuospatial processing. Taken together, these data suggest a domain‐general role for left RLPFC in monitoring and/or integrating task‐relevant knowledge representations and showcase how its function cannot solely be attributed to episodic memory or analogical reasoning computations. Hum Brain Mapp 37:896–912, 2016. © 2015 Wiley Periodicals, Inc.
Presurgical brain mapping of the language network in patients with brain tumors using resting‐state fMRI: Comparison with task fMRI
Authors: Sair Haris I. , Yahyavi‐Firouz‐Abadi Noushin , Calhoun Vince D. , Airan Raag D. , Agarwal Shruti , Intrapiromkul Jarunee , Choe Ann S. , Gujar Sachin K. , Caffo Brian , Lindquist Martin A. , Pillai Jay J.
Published: December 2015

Purpose

To compare language networks derived from resting‐state fMRI (rs‐fMRI) with task‐fMRI in patients with brain tumors and investigate variables that affect rs‐fMRI vs task‐fMRI concordance.

Materials and Methods

Independent component analysis (ICA) of rs‐fMRI was performed with 20, 30, 40, and 50 target components (ICA20 to ICA50) and language networks identified for patients presenting for presurgical fMRI mapping between 1/1/2009 and 7/1/2015. 49 patients were analyzed fulfilling criteria for presence of brain tumors, no prior brain surgery, and adequate task‐fMRI performance. Rs‐vs‐task‐fMRI concordance was measured using Dice coefficients across varying fMRI thresholds before and after noise removal. Multi‐thresholded Dice coefficient volume under the surface (DiceVUS) and maximum Dice coefficient (MaxDice) were calculated. One‐way Analysis of Variance (ANOVA) was performed to determine significance of DiceVUS and MaxDice between the four ICA order groups. Age, Sex, Handedness, Tumor Side, Tumor Size, WHO Grade, number of scrubbed volumes, image intensity root mean square (iRMS), and mean framewise displacement (FD) were used as predictors for VUS in a linear regression.

Results

Artificial elevation of rs‐fMRI vs task‐fMRI concordance is seen at low thresholds due to noise. Noise‐removed group‐mean DiceVUS and MaxDice improved as ICA order increased, however ANOVA demonstrated no statistically significant difference between the four groups. Linear regression demonstrated an association between iRMS and DiceVUS for ICA30‐50, and iRMS and MaxDice for ICA50.

Conclusion

Overall there is moderate group level rs‐vs‐task fMRI language network concordance, however substantial subject‐level variability exists; iRMS may be used to determine reliability of rs‐fMRI derived language networks. Hum Brain Mapp 37:913–923, 2016. © 2015 Wiley Periodicals, Inc.
Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma
Authors: Zhou Chuan‐chuan , Yang Fu , Yuan Sheng‐xian , Ma Jin‐zhao , Liu Feng , Yuan Ji‐hang , Bi Feng‐rui , Lin Kong‐ying , Yin Jian‐hua , Cao Guang‐wen , Zhou Wei‐ping , Wang Fang , Sun Shu‐han
Published: December 2015

Systemic analyses using large‐scale genomic profiles have successfully identified cancer‐driving somatic copy number variations (SCNVs) loci. However, functions of vast focal SCNVs in “protein‐coding gene desert” regions are largely unknown. The integrative analysis of long noncoding RNA (lncRNA) expression profiles with SCNVs in hepatocellular carcinoma (HCC) led us to identify the recurrent deletion of lncRNA‐PRAL (p53 regulation‐associated lncRNA) on chromosome 17p13.1, whose genomic alterations were significantly associated with reduced survival of HCC patients. We found that lncRNA‐PRAL could inhibit HCC growth and induce apoptosis in vivo and in vitro through p53. Subsequent investigations indicated that the three stem‐loop motifs at the 5′ end of lncRNA‐PRAL facilitated the combination of HSP90 and p53 and thus competitively inhibited MDM2‐dependent p53 ubiquitination, resulting in enhanced p53 stability. Additionally, in vivo lncRNA‐PRAL delivery efficiently reduced intrinsic tumors, indicating its potential therapeutic application. Conclusions: lncRNA‐PRAL, one of the key cancer‐driving SCNVs, is a crucial stimulus for HCC growth and may serve as a potential target for antitumor therapy. (Hepatology 2016;63:850‐863)
Target‐selectivity of parvalbumin‐positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals
Authors: Armstrong Caren , Wang Jessica , Yeun Lee Soo , Broderick John , Bezaire Marianne J. , Lee Sang‐Hun , Soltesz Ivan
Published: December 2015

The medial entorhinal cortex layer II (MEClayerII) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin‐containing basket cells (CCKBCs) select their targets on the basis of the long‐range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin‐containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non‐perforant path forming calbindin‐containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low‐dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin‐containing principal cells in MEClayerII. However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin‐containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII. However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII. Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. © 2015 Wiley Periodicals, Inc.
Age‐specific prevalence of HPV16/18 genotypes in cervical cancer: A systematic review and meta‐analysis
Authors: Hammer Anne , Rositch Anne , Qeadan Fares , Gravitt Patti E , Blaakaer Jan
Published: December 2015

The prevalence of HPV16/18 in cervical cancer has been reported to decline with age in some papers. However, whether this decline in proportion of cancers positive for HPV16/18 is consistently observed across studies remains to be elucidated. Thus, the aim of this study was to identify papers reporting data on age‐specific prevalence of HPV16/18 in cervical cancer and to summarize the results. We employed MEDLINE and Embase for a systematic literature search and thereby identified a total of 644 papers published in the period 1999–2015, of which 15 papers, reporting cross‐sectional data, were included for review (11,526 cervical cancers). The prevalence of HPV16/18 in cervical cancer declined significantly with age (ρ = −0.83, p = 0.04) from 74.8% (95% CI 67.6–80.8) in women aged 30–39 years to 56.8% (95% CI 43.9–68.8) in women aged ≥70 years. As the HPV16/18 positive cancers are prevented in fully vaccinated cohorts, the age‐specific epidemiology of cervical cancer is anticipated to change, with a shift in peak incidence rate to older ages. It will be important for integrated vaccination and screening strategies to consider predicted change in the age‐specific epidemiology of cervical cancer.
Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis
Authors: Zhang Lingtian , Kurogi Katsuhisa , Liu Ming‐Yih , Schnapp Alaina M. , Williams Frederick E. , Sakakibara Yoichi , Suiko Masahito , Liu Ming‐Cheh
Published: December 2015

The aim of the present study was to identify human cytosolic sulfotransferases (SULTs) that are capable of sulfating benzyl alcohol and to examine whether benzyl alcohol sulfation may occur in cultured human cells as well as in human organ homogenates. A systematic analysis revealed that of the 13 known human SULTs, SULT1A1 SULT1A2, SULTA3, and SULT1B1 are capable of mediating the sulfation of benzyl alcohol. The kinetic parameters of SULT1A1 that showed the strongest benzyl alcohol‐sulfating activity were determined. HepG2 human hepatoma cells were used to demonstrate the generation and release of sulfated benzyl alcohol under the metabolic settings. Moreover, the cytosol or S9 fractions of human liver, lung, kidney and small intestine were examined to verify the presence of benzyl alcohol sulfating activity in vivo. Copyright © 2015 John Wiley & Sons, Ltd.
Vitamin D Levels in Takayasu's Arteritis and a Review of the Literature on Vasculitides
Authors: Alibaz‐Oner Fatma , Asmaz‐Haliloglu Özlem , Gogas‐Yavuz Dilek , Can Meryem , Haklar Goncagul , Direskeneli Haner
Published: December 2015

Objective

Takayasu's arteritis (TAK) is a chronic, large‐vessel vasculitis. Vitamin D, as a steroidal hormone, has recently been shown to have immunoregulatory and immunosuppressive effects. Low vitamin D levels are demonstrated in various autoimmune disorders. The aim of this study is to investigate vitamin D levels in patients with TAK. A comprehensive review of vitamin D levels in systemic vasculitides (SVs) is also performed.

Methods

The study included 36 patients with TAK, 28 patients with Behçet's disease (BD) as disease control and 30 sex‐matched healthy controls. Plasma 25‐hydroxy vitamin D (25(OH) vit D) levels were measured with high‐performance liquid chromatography. “Deficiency” was defined as 25(OH) vit D levels below 25 nmol/l and “insufficiency” as below 50 nmol/l.

Results

Plasma 25(OH) vit D levels were significantly lower in TAK patients (16.93 ± 10.62 nmol/l) than healthy controls (64.63 ± 21.82 nmol/l). Vitamin D level in BD patients (38.8 ± 20.9 nmol/l) is lower than healthy controls but higher than TAK patients. The frequency of vitamin D deficiency was 83.3% in patients with TAK compared to 3.3% in healthy controls. Plasma 25(OH) vit D levels were same between clinically active and inactive patients. In literature review, very few studies were found to investigate vitamin D in SVs.

Conclusion

We observed a high prevalence of vitamin D deficiency in patients with TAK. As various immune effects of vitamin D on mononuclear cells and arterial endothelium is shown, vitamin D deficiency can be a predisposing factor for immune activation in SV. We therefore suggest monitorization and replacement of vitamin D status in all TAK and other SV patients.
Reproductive periodicity, spawning induction, and larval metamorphosis of the hemichordate acorn worm Ptychodera flava
Authors: Lin Ching‐Yi , Tung Che‐Huang , Yu Jr‐Kai , Su Yi‐Hsien
Published: December 2015

The indirect‐developing enteropneust acorn worm Ptychodera flava has been used as a hemichordate model system for studying the developmental evolution of deuterostome body plans and the origins of chordate characteristics. However, research progress has been hindered by the limited accessibility of its embryonic materials and metamorphosing larvae. In this study, we identified an abundant population of P. flava in Penghu, Taiwan, and examined the feasibility of using this animal for developmental studies. Through histological examination, we established that the reproductive season of this population is between September and December, with a peak breeding period in October and November. In addition, we have developed new procedures that can induce P. flava spawning at any time of the day during the breeding season, with a higher successful rate than that achieved using a previously published method. Moreover, the culturing system we developed enables rearing of P. flava larvae through various planktonic stages and eventual metamorphosis into benthic juveniles, all under laboratory conditions. We anticipate that the animal resources and new technical procedures reported here will further facilitate the use of P. flava as a model organism for evolutionary and developmental biology research. J. Exp. Zool. (Mol. Dev. Evol.) 326B:47–60, 2016. © 2015 Wiley Periodicals, Inc.
Whole‐brain amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging in glioma patients using low‐power steady‐state pulsed chemical exchange saturation transfer (CEST) imaging at 7T
Authors: Heo Hye‐Young , Jones Craig K. , Hua Jun , Yadav Nirbhay , Agarwal Shruti , Zhou Jinyuan , van Zijl Peter C.M. , Pillai Jay J.
Published: December 2015

Purpose

To explore the relationship of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signal intensities with respect to different World Health Organization (WHO) brain tumor grades (II to IV) at 7T.

Materials and Methods

APT‐based and NOE‐based signals at 7T using low‐power steady‐state chemical exchange saturation transfer (CEST) were compared among de novo primary gliomas of different WHO grades (II to IV). The quantitative APT and NOE signals, calculated by fitting approach using extrapolated semisolid MT reference (EMR) signals, were compared with the magnetization transfer ratio asymmetry (MTRasym) analysis, commonly used in APT‐weighted MRI.

Results

The observed NOE signals of all glioma grades were significantly lower than normal brain tissue (P < 0.01). NOE signals significantly differed between low‐grade (II) gliomas and high‐grade (III, IV) gliomas (P < 0.05). APT signals showed no difference between the tumor regions for any glioma grades (M = 3.08%, 2.64%, and 3.10%, 95% confidence interval [CI] = 2.81% ∼ 3.33%, 2.36% ∼ 2.91%, and 2.85% ∼ 3.36% for grade II, III, and IV, respectively), and between normal brain tissue and all glioma grades (P = 0.08, M = 4.29% and 2.94%, 95% CI = 3.57% ∼ 4.99% and 2.47% ∼ 3.41% for normal and average grade II, III, and IV), while MTRasym differed significantly between normal tissue and all glioma grades (P < 0.05).

Conclusion

NOE contributes substantially to APT‐weighted MRI at 7T at low RF saturation power and provides a promising biomarker for glioma grading.J. Magn. Reson. Imaging 2016;44:41–50.
Vortex‐ring mixing as a measure of diastolic function of the human heart: Phantom validation and initial observations in healthy volunteers and patients with heart failure
Authors: Töger Johannes , Kanski Mikael , Arvidsson Per M. , Carlsson Marcus , Kovács Sándor J. , Borgquist Rasmus , Revstedt Johan , Söderlind Gustaf , Arheden Håkan , Heiberg Einar
Published: December 2015

Purpose

To present and validate a new method for 4D flow quantification of vortex‐ring mixing during early, rapid filling of the left ventricle (LV) as a potential index of diastolic dysfunction and heart failure.

Materials and Methods

4D flow mixing measurements were validated using planar laser‐induced fluorescence (PLIF) in a phantom setup. Controls (n = 23) and heart failure patients (n = 23) were studied using 4D flow at 1.5T (26 subjects) or 3T (20 subjects) to determine vortex volume (VV) and inflowing volume (VVinflow). The volume mixed into the vortex‐ring was quantified as VVmix‐in = VV–VVinflow. The mixing ratio was defined as MXR = VVmix‐in/VV. Furthermore, we quantified the fraction of the end‐systolic volume (ESV) mixed into the vortex‐ring (VVmix‐in/ESV) and the fraction of the LV volume at diastasis (DV) occupied by the vortex‐ring (VV/DV).

Results

PLIF validation of MXR showed fair agreement (R2 = 0.45, mean ± SD 1 ± 6%). MXR was higher in patients compared to controls (28 ± 11% vs. 16 ± 10%, P < 0.001), while VVmix‐in/ESV and VV/DV were lower in patients (10 ± 6% vs. 18 ± 12%, P < 0.01 and 25 ± 8% vs. 50 ± 6%, P < 0.0001).

Conclusion

Vortex‐ring mixing can be quantified using 4D flow. The differences in mixing parameters observed between controls and patients motivate further investigation as indices of diastolic dysfunction. J. Magn. Reson. Imaging 2016;43:1386–1397.
Bioprospecting around Arctic islands: Marine bacteria as rich source of biocatalysts
Authors: De Santi Concetta , Altermark Bjørn , de Pascale Donatella , Willassen Nils‐Peder
Published: December 2015

We have investigated the biotechnological potential of Arctic marine bacteria for their ability to produce a broad spectrum of cold‐active enzymes. Marine bacteria exhibiting these features are of great interest for both fundamental research and industrial applications. Macrobiota, water and sediment samples have been collected during 2010 and 2011 expeditions around the Lofoten and Svalbard islands. Bacteria were isolated from this material and identified through 16S rRNA gene sequence analysis for the purpose of establishing a culture collection of marine Arctic bacteria. Herein, we present the functional screening for different extracellular enzymatic activities from 100 diversely chosen microbial isolates incubated at 4 and 20 °C. The production of esterase/lipase, DNase, and protease activities were revealed in 67, 53, and 56% of the strains, respectively, while 41, 23, 9, and 7% of the strains possessed amylase, chitinase, cellulase, and xylanase activities, respectively. Our findings show that phylogenetically diverse bacteria, including many new species, could be cultured from the marine arctic environment. The Arctic polar environment is still an untapped reservoir of biodiversity for bioprospecting.
Late Holocene fluctuations of Quelccaya Ice Cap, Peru, registered by nearby lake sediments
Authors: Stroup Justin S. , Kelly Meredith A. , Lowell Thomas V. , Smith Colby A. , Beal Samuel A. , Landis Joshua D. , Tapia Pedro M.
Published: December 2015

Records of clastic sediment from lakes that receive glacial meltwater provide a means for inferring past glacial fluctuations. However, increased clastic sedimentation has been interpreted to indicate both glacial advance and recession. Here we examine the timing of clastic sediment deposition in Challpacocha, a glacially fed lake located downvalley from Quelccaya Ice Cap (QIC), Peru, in comparison with known ice cap margin fluctuations. Using a comparison with a nearby non‐glacial lake, Yanacocha, we document that a record of clastic sediment flux from Challpacocha reflects meltwater‐derived sediment. We then compare the clastic sediment record from Challpacocha with the Qori Kalis glacier moraine record. We find that organic‐rich sediment was deposited primarily during the late Holocene advance of QIC (before ∼CE 1490). In contrast, clastic sediment was deposited during QIC recession (∼CE 1490–1970). Peaks in clastic sediment flux are associated with the onset of ice retreat. We suggest that this pattern of clastic sediment deposition reflects changing meltwater production and/or glacial erosion during ice advance and retreat and supports models of increased clastic sedimentation during ice retreat.
Cosmogenic dating of Late Pleistocene glaciation, southern tropical Andes, Peru
Authors: Shakun Jeremy D. , Clark Peter U. , Marcott Shaun A. , Brook Edward J. , Lifton Nathaniel A. , Caffee Marc , Shakun William R.
Published: December 2015

We present 30 10Be dates on three moraines formed by small glaciers in the southern tropical Andes of Peru to determine the timing of the local Last Glacial Maximum (LGM) and subsequent deglaciation. Two terminal moraines indicate that the local LGM ended at 23.5 ± 0.5 and 21.2 ± 0.8 ka, or well before the end of the global LGM (20–19 ka). A recessional moraine perched at the base of a steep valley wall has a 10Be age of 19.8 ± 0.3 ka, suggesting that glaciers had largely retreated from the area during the earliest stages of the last termination and before the onset of the deglacial CO2 rise and increase in tropical sea surface temperatures. These ages generally agree with other tropical glacial chronologies and reflect a broad synchroneity between low‐ and high‐latitude deglaciation at the LGM, but the trigger for early deglaciation of the tropics remains unclear.
Comprehensive multiplatform biomarker analysis of 350 hepatocellular carcinomas identifies potential novel therapeutic options
Authors: Ang Celina , Miura John T. , Gamblin T. Clark , He Ruth , Xiu Joanne , Millis Sherri Z. , Gatalica Zoran , Reddy Sandeep K. , Yee Nelson S. , Abou‐Alfa Ghassan K.
Published: December 2015

Background and Objectives

Effective therapies for hepatocellular carcinoma (HCC) are limited. Molecular profiling of HCC was performed to identify novel therapeutic targets.

Methods

350 HCC samples were evaluated using a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ), including gene sequencing, amplification, and protein expression.

Results

EGFR, TOPO1, PD‐1, TOP2A, SPARC, and c‐Met were overexpressed in 25–83% of samples. Decreased expression of RRM1,TS, PTEN, and MGMT occurred in 31–82% of samples. TP53 was mutated in 30%, CTNNB1 in 20%, and BRCA2 in 18%; other gene mutation rates were <5%. TP53‐mutated tumors showed significantly higher TOPO2A (90% vs. 38%, P < 0.0001) and TS (56% vs. 29%, P = 0.0139) expression. CTNNB1‐mutated tumors had significantly higher AR (56% vs. 21%, P = 0.0017), SPARC (61% vs. 29%, P = 0.0135), PDL1 (29% vs. 0%, P = 0.0256) expression, and BRCA2 mutations (50% vs. 6%, P = 0.0458). Metastases exhibited significantly higher infiltration by PD‐1+ lymphocytes (79% vs. 50%, P = 0.047) and TS (31% vs. 14%, P < 0.0003) than primary HCC.

Conclusions

Multiplatform profiling reveals molecular heterogeneity in HCC and identifies potential therapies including tyrosine kinase, PI3 kinase, or PARP inhibitors for molecular subtypes. Chemotherapy may benefit some tumors. CTNNB1‐mutated tumors may respond to multi‐target inhibition. These limited and preliminary data require clinical validation. J. Surg. Oncol. 2016;113:55–61. © 2015 Wiley Periodicals, Inc.
Impact of surgical margin clearance for resection of secondary hepatic malignancies
Authors: Bhutiani Neal , Philips Prejesh , Martin Robert C.G. , Scoggins Charles R.
Published: December 2015

Over the past several decades, there has been increasing discussion regarding the optimal management of secondary liver malignancies. Traditionally, resection has only been recommended if it could be accomplished with negative microscopic margins of at least 10 mm. However, many investigators have pushed this limit to offer resection to patients with narrower margins. We review the data regarding the impact of margin clearance on outcomes for patients undergoing hepatic metastasectomy. J. Surg. Oncol. 2016;113:289–295. © 2015 Wiley Periodicals, Inc.
The importance of surgical margins in gastric cancer
Authors: Postlewait Lauren M. , Maithel Shishir K.
Published: December 2015

Interpretation and management of the surgical margin is paramount to the treatment of gastric adenocarcinoma. Although in early‐stage disease, a microscopically positive margin may be associated with poor outcomes, in later stages, it does not persist as an independent poor prognostic factor but rather is likely a marker of other adverse pathologic characteristics that ultimately determine outcomes. Thus, the decision to extend a resection to achieve a negative margin should be deliberate and individualized. J. Surg. Oncol. 2016;113:277–282. © 2015 Wiley Periodicals, Inc.
The role of margins in extremity soft tissue sarcoma
Authors: Byerly Saskya , Chopra Shefali , Nassif Nader A. , Chen Peter , Sener Stephen F. , Eisenberg Burton L. , Tseng William W.
Published: December 2015

For extremity soft tissue sarcomas, limb salvage is now standard of care. The extent of surgical margins is balanced with functionality of the resected limb. Although negative margins are the goal, the necessary width is unclear. Additional considerations for margin adequacy include presence of anatomic barriers such as fascia and periosteum, proximity of critical structures, receipt of adjuvant and neoadjuvant therapies, and histologic subtype. Multidisciplinary team discussion is critical for treatment planning. J. Surg. Oncol. 2016;113:333–338. © 2015 Wiley Periodicals, Inc.
Low intensity 635 nm diode laser irradiation inhibits fibroblast–myofibroblast transition reducing TRPC1 channel expression/activity: New perspectives for tissue fibrosis treatment
Authors: Sassoli Chiara , Chellini Flaminia , Squecco Roberta , Tani Alessia , Idrizaj Eglantina , Nosi Daniele , Giannelli Marco , Zecchi‐Orlandini Sandra
Published: December 2015

BACKGROUND AND OBJECTIVE

Low‐level laser therapy (LLLT) or photobiomodulation therapy is emerging as a promising new therapeutic option for fibrosis in different damaged and/or diseased organs. However, the anti‐fibrotic potential of this treatment needs to be elucidated and the cellular and molecular targets of the laser clarified. Here, we investigated the effects of a low intensity 635 ± 5 nm diode laser irradiation on fibroblast–myofibroblast transition, a key event in the onset of fibrosis, and elucidated some of the underlying molecular mechanisms.

MATERIALS AND METHODS

NIH/3T3 fibroblasts were cultured in a low serum medium in the presence of transforming growth factor (TGF)‐β1 and irradiated with a 635 ± 5 nm diode laser (continuous wave, 89 mW, 0.3 J/cm2). Fibroblast–myofibroblast differentiation was assayed by morphological, biochemical, and electrophysiological approaches. Expression of matrix metalloproteinase (MMP)‐2 and MMP‐9 and of Tissue inhibitor of MMPs, namely TIMP‐1 and TIMP‐2, after laser exposure was also evaluated by confocal immunofluorescence analyses. Moreover, the effect of the diode laser on transient receptor potential canonical channel (TRPC) 1/stretch‐activated channel (SAC) expression and activity and on TGF‐β1/Smad3 signaling was investigated.

RESULTS

Diode laser treatment inhibited TGF‐β1‐induced fibroblast–myofibroblast transition as judged by reduction of stress fibers formation, α‐smooth muscle actin (sma) and type‐1 collagen expression and by changes in electrophysiological properties such as resting membrane potential, cell capacitance and inwardly rectifying K+ currents. In addition, the irradiation up‐regulated the expression of MMP‐2 and MMP‐9 and downregulated that of TIMP‐1 and TIMP‐2 in TGF‐β1‐treated cells. This laser effect was shown to involve TRPC1/SAC channel functionality. Finally, diode laser stimulation and TRPC1 functionality negatively affected fibroblast–myofibroblast transition by interfering with TGF‐β1 signaling, namely reducing the expression of Smad3, the TGF‐β1 downstream signaling molecule.

CONCLUSION

Low intensity irradiation with 635 ± 5 nm diode laser inhibited TGF‐β1/Smad3‐mediated fibroblast–myofibroblast transition and this effect involved the modulation of TRPC1 ion channels. These data contribute to support the potential anti‐fibrotic effect of LLLT and may offer further informations for considering this therapy as a promising therapeutic tool for the treatment of tissue fibrosis. Lasers Surg. Med. 48:318–332, 2016. © 2015 Wiley Periodicals, Inc.
Short‐term microbiological effects of photodynamic therapy in non‐surgical periodontal treatment of residual pockets: A split‐mouth RCT
Authors: Corrêa Mônica Grazieli , Oliveira Deborah Haydee , Saraceni Cintia Helena Coury , Ribeiro Fernanda Vieira , Pimentel Suzana Peres , Cirano Fabiano Ribeiro , Casarin Renato Corrêa Viana
Published: December 2015

Background and Objective

Photodynamic therapy (PDT) has been used as a therapeutic alternative to treat periodontitis, especially in challenging sites that require additional periodontal therapy such as residual pockets. The aim of this split‐mouth randomized trial was to evaluate the microbiological and clinical effects of PDT on non‐surgical treatment of unresponsive pockets.

Study Design/Materials and Methods

A split‐mouth, randomized controlled clinical trial was conducted in 15 patients presenting at least two residual pockets (probing pocket depth [PPD] ≥5 mm with bleeding on probing [BoP]) in single‐rooted teeth in supportive periodontal therapy. The selected sites randomly received: (1) SRP + PDT: scaling and root planing combined with photodynamic therapy (methylene blue as a photosensitizer), or (2) SRP: scaling and root planing alone. The concentrations of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were evaluated using a Real‐time PCR technique at baseline and 3, 7, 14, and 90 days. Clinical parameters were assessed at baseline and 3 months post‐therapies.

Results

Both treatments promoted clinical improvements, with additional benefits to the SRP + PDT group in PPD reduction and clinical attachment level gain (P < 0.05) after 3 months. Only the SRP + PDT group exhibited a statistically significant reduction in the levels of A. actinomycetemcomitans on the 3rd and 7th days after therapy (P < 0.05), and a lower concentration of this pathogen was detected at 7 days in the SRP + PDT group when compared to the other therapy (P < 0.05).

Conclusion

The combined therapeutic approach SRP + PDT may reduce A. actinomycetemcomitans levels for a short‐term period, associated with additional improvement in clinical parameters in treating residual pockets. Lasers Surg. Med. 48:944–950, 2016. © 2015 Wiley Periodicals, Inc.
THE RISE OF TRUE NORTH LEADERS
Authors: George Bill
Published: December 2015

According to George, many of the high profile business failures and bankruptcies of recent years were caused by leadership failures. Wrongly‐chosen CEOs “put their companies at risk by focusing on the spoils of leadership instead of building organizations for the long‐term.” We need instead authentic, values‐based people, whom he calls “True North Leaders.” George points out that “trust is the coin of the realm” in business, and trust has been seriously eroded. In showing how leaders can discover their True North, he draws on his research and anecdotes from his own life, including his decision to accept a position as CEO of Medtronic, from which he retired in 2002.
The role of indium in the activation of aluminum alloy galvanic anodes
Authors: Pourgharibshahi M. , Lambert P.
Published: December 2015

Despite six decades use of aluminum as a galvanic (sacrificial) anode, there remains a need for a better understanding of the underlying mechanisms for enhancing its efficient performance in cathodic protection systems. A few mechanisms have been proposed for the role of indium in the activation of Al‐Zn‐In anodes and there appears to be no general agreement on whether this element plays its depassivating role by modifying the bulk microstructure of the anode, chemical composition of its surrounding electrolyte or directly through doping the structure of the passive oxide film. These mechanisms have been critically reviewed to achieve a more comprehensive understanding of the role of indium in such applications. Moreover, the novel solidification processing called controlled diffusion solidification (CDS) has been introduced as an efficient way to surmount the poor castability of the anode alloy without any need for the addition of elements with detrimental effects on the electrochemical properties of the anode.
The Effects of Psychobiological Motivational Traits on Memory of In‐Game Advertising Messages
Authors: Sparks Johnny V. , Chung Sungwon
Published: December 2015

This study examined the influence of psychobiological motivational traits related to individual approach and avoidance tendencies on cognitive processing of in‐game advertising. Participants played a custom‐built video game containing billboard advertisements. After playing the game, participants’ approach, positivity offset (PO), and avoidance, negativity bias (NB), traits were measured using the motivation activation measure (MAM). Recognition and recall memory were greater for high PO and low NB trait individuals. The findings of this study imply that advertising in first‐person‐shooter (FPS) video games may be most effective when targeting individuals with simultaneously high PO and low NB, risk takers, but least effective for those with low PO and high NB, risk avoiders.
Differences and Similarities between Impulse Buying and Variety Seeking: A Personality‐based Perspective
Authors: Olsen Svein Ottar , Tudoran Ana Alina , Honkanen Pirjo , Verplanken Bas
Published: December 2015

Although personality is a key determinant of consumer purchasing decision making, the role of personality traits in impulse buying and variety seeking is not conclusive. This research uses a personality perspective to determine the unique associations among impulse buying tendency (IBT), variety seeking tendency (VST), and the Big Five personality traits within one integrated framework. Based on data from a nationally representative sample of 1644 Norwegian adults, the results show that while IBT and VST might be correlated, they differ significantly with respect to two major personality aspects: “neuroticism” and “openness to experience.” Specifically, the present study indicates that neuroticism predicted IBT positively and VST negatively, while openness was a strong predictor of VST and unrelated to IBT.
When Your Source Is Smiling, Consumers May Automatically Smile with You: Investigating the Source Expressive Display Hypothesis
Authors: Kulczynski Alicia , Ilicic Jasmina , Baxter Stacey M.
Published: December 2015

Facial expressions act as a powerful readout device, influencing a viewer's own emotional response. Drawing from facial feedback theory, the mediating role of source expressive display‐based judgments on the influence of source facial expressions on consumer attitudes toward advertising stimuli, attitudes toward endorsed brands, and behavioral intention is examined. In addition, the examination of expressive display‐based judgments as an automatic phenomenon, contingent on the familiarity of the source and the perceived match with the product endorsed is investigated. Across three studies, the facial expression of a source (resting vs. smiling) is manipulated within endorsement contexts. Results demonstrate that when an endorser is pictured in an advertisement with a smiling facial expression, consumers report feeling more pleasant (pleasure), with this positive emotional response mediating the relationship between source expressive display and attitude toward an advertisement, attitude toward a brand, and purchase intention. Results also indicate that the emotional response derived from the presence of a smiling source in an advertisement occurs effortlessly, yet only for a familiar source and one that is perceived to match the product endorsed, indicating this process can be defined as automatic under certain conditions. The findings from these studies provide advertisers with an effective cue to enhance a consumer's emotional response to advertisements, which in turn heighten advertisement, brand, and behavioral based judgments.
Chemical characterisation of Nigerian red propolis and its biological activity against Trypanosoma Brucei
Authors: Omar Ruwida M. K. , Igoli John , Gray Alexander I. , Ebiloma Godwin Unekwuojo , Clements Carol , Fearnley James , Edrada Ebel Ru Angeli , Zhang Tong , De Koning Harry P. , Watson David G.
Published: December 2015

Introduction

A previous study showed the unique character of Nigerian red propolis from Rivers State, Nigeria (RSN), with regards to chemical composition and activity against Trypanosoma brucei in comparison with other African propolis.

Objective

To carry out fractionation and biological testing of Nigerian propolis in order to isolate compounds with anti‐trypanosomal activity. To compare the composition of the RSN propolis with the composition of Brazilian red propolis.

Methodology

Profiling was carried out using HPLC‐UV‐ELSD and HPLC‐Orbitrap‐FTMS on extracts of two samples collected from RSN with data extraction using MZmine software. Isolation was carried out by normal phase and reversed phase MPLC. Elucidation of the compounds with a purity > 95% was performed by 1D/2D NMR HRMS and HRLC‐MSn.

Results

Ten phenolic compounds were isolated or in the case of liquiritigenin partially purified. Data for nine of these correlated with literature reports of known compounds i.e. one isoflavanone, calycosin (1); two flavanones, liquiritigenin (2) and pinocembrin (5); an isoflavan, vestitol (3); a pterocarpan, medicarpin (4); two prenylflavanones, 8‐prenylnaringenin (7) and 6‐prenylnaringenin (8); and two geranyl flavonoids, propolin D (9) and macarangin (10). The tenth was elucidated as a previously undescribed dihydrobenzofuran (6). The isolated compounds were tested against Trypanosoma brucei and displayed moderate to high activity. Some of the compounds tested had similar activity against wild type T. brucei and two strains displaying pentamidine resistance.

Conclusion

Nigerian propolis from RSN has some similarities with Brazilian red propolis. The propolis displayed anti‐trypanosomal activity at a potentially useful level. Copyright © 2015 John Wiley & Sons, Ltd.
Role of family caregivers' self‐perceived preparedness for the death of the cancer patient in long‐term adjustment to bereavement
Authors: Kim Youngmee , Carver Charles S. , Spiegel David , Mitchell Hannah‐Rose , Cannady Rachel S.
Published: December 2015

Background

A substantial number of family caregivers go through bereavement because of cancer, but little is known about the bereaved caregivers' long‐term adjustment. This study aimed to document levels of bereavement outcomes (prolonged grief symptoms, intense emotional reaction to the loss, depressive symptoms, and life satisfaction) among family cancer caregivers 3–5 years post‐loss and to investigate how self‐rated preparedness for the patient's death predicted those bereavement outcomes.

Methods

Family members participated in a nationwide survey for cancer caregivers 2 years after the relative's diagnosis (T1). Of those, 109 were identified as bereaved by 5 years post‐diagnosis (T2). Of those, 88 continued to participate at 8‐year follow‐up (T3) and provided valid data for the study variables. Caregivers' distress risk factors were measured at T1, satisfaction with palliative care and preparedness for the death of the patient at T2, and time since death of the patient at T2 or T3.

Results

Substantial numbers of family members (18% to 48%) displayed heightened levels of bereavement‐related psychological distress years after the loss. Hierarchical general linear modeling revealed that perceived preparedness for the death of the patient concurrently and prospectively predicted better adjustment to bereavement, independent of contributions of other factors studied.

Conclusions

Findings underscore the high prevalence of long‐lasting bereavement‐related distress among family cancer caregivers and the role of preparedness for the relative's death in the level of that distress. Findings suggest that psychosocial programs among caregivers focus on not only caregiving skills per se but also preparedness for the death of the patient. Copyright © 2015 John Wiley & Sons, Ltd.
Anti‐inflammatory and anti‐endotoxin properties of peptides derived from the carboxy‐terminal region of a defensin from the tick Ornithodoros savignyi
Authors: Malan Melissa , Serem June C. , Bester Megan J. , Neitz Albert W. H. , Gaspar Anabella R. M.
Published: December 2015

Antimicrobial peptides are small cationic peptides that possess a large spectrum of bioactivities, including antimicrobial, anti‐inflammatory and antioxidant activities. Several antimicrobial peptides are known to inhibit lipopolysaccharide (LPS)‐induced inflammation in vitro and to protect animals from sepsis. In this study, the cellular anti‐inflammatory and anti‐endotoxin activities of Os and Os‐C, peptides derived from the carboxy‐terminal of a tick defensin, were investigated. Both Os and Os‐C were found to bind LPS in vitro, albeit to a lesser extent than polymyxin B and melittin, known endotoxin‐binding peptides. Binding to LPS was found to reduce the bactericidal activity of Os and Os‐C against Escherichia coli confirming the affinity of both peptides for LPS. At a concentration of 25 µM, the nitric oxide (NO) scavenging activity of Os was higher than glutathione, a known NO scavenger. In contrast, Os‐C showed no scavenging activity. Os and Os‐C inhibited LPS/IFN‐γ induced NO and TNF‐α production in RAW 264.7 cells in a concentration‐dependent manner, with no cellular toxicity even at a concentration of 100 µM. Although inhibition of NO and TNF‐α secretion was more pronounced for melittin and polymyxin B, significant cytotoxicity was observed at concentrations of 1.56 µM and 25 µM for melittin and polymyxin B, respectively. In addition, Os, Os‐C and glutathione protected RAW 264.7 cells from oxidative damage at concentrations as low as 25 µM. This study identified that besides previously reported antibacterial activity of Os and Os‐C, both peptides have in addition anti‐inflammatory and anti‐endotoxin properties. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.