bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the VA and NIDILRR TBI Model System Cohorts
Authors: Nakase-Richardson Risa , Stevens Lillian Flores , Tang Xinyu , Lamberty Greg J. , Sherer Mark , Walker William C. , Pugh Mary Jo , Eapen Blessen C. , Finn Jacob A. , Saylors Mimi , Dillahunt-Aspillaga Christina , Adams Rachel Sayko , Garofano Jeffrey S.
Published: July 2017

Objective:

Within the same time frame, compare the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) and VA Traumatic Brain Injury Model System (TBIMS) data sets to inform future research and generalizability of findings across cohorts.

Setting:

Inpatient comprehensive interdisciplinary rehabilitation facilities.

Participants:

Civilians, Veterans, and active duty service members in the VA (n = 550) and NIDILRR civilian settings (n = 5270) who were enrolled in TBIMS between August 2009 and July 2015.

Design:

Prospective, longitudinal, multisite study.

Main Measures:

Demographics, Injury Characteristics, Functional Independence Measures, Disability Rating Scale.

Results:

VA and NIDILRR TBIMS participants differed on 76% of comparisons (18 Important, 8 Minor), with unique differences shown across traumatic brain injury etiology subgroups. The VA cohort was more educated, more likely to be employed at the time of injury, utilized mental health services premorbidly, and experienced greater traumatic brain injury severity. As expected, acute and rehabilitation lengths of stay were longer in the VA with no differences in death rate found between cohorts.

Conclusions:

Substantial baseline differences between the NIDILRR and VA TBIMS participants warrant caution when comparing rehabilitation outcomes. A substantive number of NIDILRR enrollees had a history of military service (>13%) warranting further focused study. The TBIMS participant data collected across cohorts can be used to help evidence-informed policy for the civilian and military-related healthcare systems.
Circuit-level Mechanisms of EtOH-dependent dopamine release
Authors: Volo Matteo di , Morozova Ekaterina O. , Lapish Christopher C. , Kuznetsov Alexey , Gutkin Boris
Published: July 2017

Alcoholism is the third leading cause of preventable mortality in the world. In the last decades a large body of experimental data has paved the way to a clearer knowledge of the specific molecular targets through which ethanol (EtOH) acts on brain circuits. Yet how these multiple mechanisms play together to result in a dysregulated dopamine (DA) release under alcohol influence remains unclear. In this manuscript, we delineate potential circuit-level mechanisms responsible for EtOH-dependent increase and dysregulation of DA release from the ventral tegmental area (VTA) into nucleus accumbens (Nac). For this purpose, we build a circuit model of the VTA composed of DA and GABAergic neurons, that integrate external Glutamatergic (Glu) inputs to result in DA release. In particular, we reproduced a non-monotonic dose dependence of DA neurons firing activity on EtOH: an increase in firing at small to intermediate doses and a drop below baseline (alcohol-free) levels at high EtOH concentrations. Our simulations predict that a certain level of synchrony is necessary for the firing rate increase produced by EtOH. Moreover, EtOH’s effect on the DA neuron’s firing rate and, consequently, DA release can reverse depending on the average activity level of the Glu afferents to VTA. Further, we propose a mechanism for emergence of transient (phasic) DA peaks and the increase in their frequency in EtOH. Phasic DA transients result from DA neuron population bursts, and these bursts are enhanced in EtOH. These results suggest the role of synchrony and average activity level of Glu afferents to VTA in shaping the phasic and tonic DA release under the acute influence of EtOH and in normal conditions.
The tumor suppressor APC is an attenuator of spindle-pulling forces duringC. elegansasymmetric cell division
Authors: Sugioka Kenji , Fielmich Lars-Eric , Mizumoto Kota , Bowerman Bruce , van den Heuvel Sander , Kimura Akatsuki , Sawa Hitoshi
Published: July 2017

The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/ß-catenin signaling and accurate chromosome segregation, and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show thatC. elegansAPR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of theC. eleganszygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle. We found that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent manner and suppresses anterior centrosome movements. Our combined cell biological and mathematical analyses support the conclusion that cortical APR-1 reduces force generation by stabilizing microtubule plus ends at the cell cortex. Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to attenuate spindle pulling forces. Our results document a physical basis for spindle-pulling force attenuation, which may be generally used in asymmetric cell division, and when disrupted potentially contributes to division defects in cancer.

Significance Statement

APC (adenomatous polyposis coli) is a Wnt signaling component as well as a microtubule-associated protein, and its mutations are frequently associated with colorectal cancers in humans. Although APC stabilizes microtubules (MTs), its mechanical role during cell division is largely unknown. Here we show that APC is an attenuator of forces acting on the mitotic spindle during asymmetric cell division of theC. eleganszygote. We performed live-imaging, laser-microsurgery, and numerical simulation to show how APC suppresses spindle pulling force generation by stabilizing microtubule plus-ends and reducing microtubule catastrophe frequency at the cell cortex. Our study is the first to document a mechanical role for the APC protein, and provides a physical basis for spindle-pulling force attenuation.
Genomic footprints of activated telomere maintenance mechanisms in cancer
Authors: Sieverling Lina , Hong Chen , Koser Sandra D. , Ginsbach Philip , Kleinheinz Kortine , Hutter Barbara , Braun Delia M. , Cortés-Ciriano Isidro , Xi Ruibin , Kabbe Rolf , Park Peter J. , Eils Roland , Schlesner Matthias , Rippe Karsten , Jones David T.W. , Brors Benedikt , Feuerbach Lars ,   on behalf of the PCAWG Structural Variation Working Group, PCAWG SNV Calling Working Group, PCAWG Drivers and Functional Interpretation Group, PCAWG Evolution and Heterogeneity Working Group, PCAWG Technical Working Group, and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: July 2017

Cancers require telomere maintenance mechanisms for unlimited replicative potential. We dissected whole-genome sequencing data of over 2,500 matched tumor-control samples from 36 different tumor types to characterize the genomic footprints of these mechanisms. While the telomere content of tumors withATRXorDAXXmutations (ATRX/DAXXtrunc) was increased, tumors withTERTmodifications showed a moderate decrease of telomere content. One quarter of all tumor samples contained somatic integrations of telomeric sequences into non-telomeric DNA. With 80% prevalence, ATRX/DAXXtrunctumors display a 3-fold enrichment of telomere insertions. A systematic analysis of telomere composition identified aberrant telomere variant repeat (TVR) distribution as a genomic marker of ATRX/DAXXtrunctumors. In this clinically relevant subgroup, singleton TTCGGG and TTTGGG TVRs (previously undescribed) were significantly enriched or depleted, respectively. Overall, our findings provide new insight into the recurrent genomic alterations that are associated with the establishment of different telomere maintenance mechanisms in cancer.
The Influence of Aging and Mechanical Stretch in Alveolar Epithelium ER Stress and Inflammation
Authors: Valentine MS , Herbert JA , Link PA , Kamga Gninzeko F , Schneck MB , Shankar K , Nkwocha J , Reynolds AM , Heise RL
Published: July 2017

Ventilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is more susceptible to lung injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. An activated response known as Endoplasmic Reticulum (ER) Stress occurs at the cellular level, which is increased with aging. The disrupted ER function results in disruption in cellular homeostasis, apoptosis, and inflammation. We hypothesized that age and mechanical stretch increase proinflammatory gene expression that is mediated by ER stress. Type II alveolar epithelial cells (ATII) were harvested from C57Bl6/J mice 8 weeks (young) and 20 months (old) of age. The cells were cyclically mechanically stretched at 15% change in surface area for up to 24 hours. Prior to stretch, groups were administered 4-PBA or vehicle as a control. Mechanical stretch upregulated both ER stress and proinflammatory gene expression in ATIIs. Age-matched and mis-matched monocyte recruitment by ATII conditioned media was quantified. Administration of 4-PBA attenuated both the ER stress and proinflammatory increases from stretch and/or age and significantly reduced monocyte migration to ATII conditioned media. Age increases susceptibility to stretch-induced ER stress and downstream inflammation in a primary ATII epithelial cell model.
Cryptography for genetic material
Authors: Sawaya Sterling
Published: July 2017

Genetic information can be highly sensitive and can be used to identify its source. To conceal genetic information, cryptographic methods can be applied to genetic material itself, concealing sensitive information prior to the generation of sequence data. The cryptographic method described here uses randomly divided subsets of barcodes and random pooling to securely generate pools of genetic material. The privacy obtained by these methods are measured here using differential privacy.
GWAS of epigenetic ageing rates in blood reveals a critical role forTERT
Authors: Lu Ake T. , Xue Luting , Salfati Elias L. , Chen Brian H. , Ferrucci Luigi , Levy Daniel , Joehanes Roby , Murabito Joanne M , Kiel Douglas P. , Tsai Pei-Chien , Yet Idil , Bell Jordana T. , Mangino Massimo , Tanaka Toshiko , McRae Allan F. , Marioni Riccardo E. , Visscher Peter M. , Wray Naomi R. , Deary Ian J. , Levine Morgan E. , Quach Austin , Assimes Themistocles , Tsao Philip S. , Absher Devin , Stewart James D. , Li Yun , Reiner Alex P. , Hou Lifang , Baccarelli Andrea A. , Whitsel Eric A. , Aviv Abraham , Cardona Alexia , Day Felix R. , Perry John R.B. , Ong Ken K. , Raj Kenneth , Lunetta Kathryn L. , Horvath Steve
Published: July 2017

DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9,907 individuals, we found gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in 3 loci associated extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggested causal influences of menarche and menopause on IEAA and lipid levels on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) locus at 5p15.33 confer higher IEAA (P<2.7×10-11). Causal modelling indicatesTERT-specific and independent effects on LTL and IEAA. Experimental hTERT expression in primary human fibroblasts engenders a linear increase in DNA methylation age with cell population doubling number. Together, these findings indicate a critical role for hTERT in regulating the DNA methylation clock, in addition to its established role of compensating for cell replication-dependent telomere shortening.
Morphometrics of complex cell shapes: Lobe Contribution Elliptic Fourier Analysis (LOCO-EFA)
Authors: Sánchez-Corrales Yara E. , Hartley Matthew , Rooij Jop van , Marée Athanasius F. M. , Grieneisen Verônica A.
Published: July 2017

Quantifying cell morphology is fundamental to the statistical study of cell populations, and can help us unravel mechanisms underlying cell and tissue morphogenesis. Current methods, however, require extensive human intervention, are highly sensitive to parameter choice, or produce metrics that are difficult to interpret biologically. We therefore developed a novel method, Lobe Contribution Elliptical Fourier Analysis (LOCO-EFA), which generates from digitalised cell outlines meaningful descriptors that can be directly matched to morphological features. We show that LOCO-EFA provides a tool to phenotype efficiently and objectively populations of cells by applying it to the complex shaped pavement cells ofArabidopsis thalianawild type andspeechlessleaves. To further validate our method, we analysed computer-generated tissues, where cell shape can be specified in a controlled manner. LOCO-EFA quantifies deviations between the specified shape that an individualin silicocell takes up when in isolation and the resultant shape when they are allowed to interact within a confluent tissue, thereby assessing the role of cell-cell interactions on population cell shape distributions.

Summary statement

Novel method (LOCO-EFA) quantifies complex cell shapes, extracting meaningful biological features such as protrusion number and amplitude; here shown for plant pavement cells and validated onin silicotissues.
SHP2 Is Required for BCR-ABL1-Induced Hematologic Neoplasms
Authors: Gu Shengqing , Sayad Azin , Chan Gordon , Yang Wentian , Lu Zhibin , Virtanen Carl , Van Etten Richard A. , Neel Benjamin G.
Published: July 2017

BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation (BMT) models for CML and BCR-ABL1+B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia.Ptpn11deletion impairs initiation and maintenance of CML-like myeloproliferative neoplasm, and compromises induction of BCR-ABL1+B-ALL. SHP2, and specifically, its SH2 domains, PTP activity and C-terminal tyrosines, is essential for BCR-ABL1+, but not WT, pre-B cell proliferation. The MEK/ERK pathway is regulated by SHP2 in WT and BCR-ABL1+pre-B cells, but is only required for the proliferation of BCR-ABL1+cells. SHP2 is required for SRC family kinase (SFK) activation only in BCR-ABL1+pre-B cells. RNAseq reveals distinct SHP2-dependent transcriptional programs in BCR-ABL1+and WT pre-B cells. Our results suggest that SHP2, via SFKs and ERK, repressesMXD3/4to facilitate a MYC-dependent proliferation program in BCR-ABL1-transformed pre-B cells.
ukbtools: An R package to manage and query UK Biobank data
Authors: Hanscombe Ken B. , Coleman Jonathan R.I , Traylor Matthew , Lewis Cathryn M.
Published: July 2017

The UK Biobank is a resource that includes detailed health-related data on about 500,000 individuals and is available to the research community. ukbtools removes all the upfront data wrangling required to get a single dataset for statistical analysis, and provides tools to assist in quality control, query of disease diagnoses, and retrieval of genetic metadata.

Availability

The package is available for installation from the Comprehensive R Archive Network (CRAN), and includes a vignette describing the use of all functionality.

Contact

 ken.b.hanscombe@kcl.ac.uk,https://github.com/kenhanscombe/ukbtools
Colorectal cancer susceptibility loci as predictive markers of rectal cancer prognosis after surgery
Authors: Hu Yue , Gaedcke Jochen , Emons Georg , Beissbarth Tim , Grade Marian , Jo Peter , Yeager Meredith , Chanock Stephen , Wolff Hendrik , Camps Jordi , Ghadimi B. Michael , Ried Thomas
Published: July 2017

Background

Colorectal cancer (CRC) is among the leading causes of cancer death. Rectal cancers account for one third of CRC cases. The role and significance of colorectal cancer risk loci in rectal cancer progression has not been investigated.

Methods

We generated and explored a dataset from 230 rectal cancer patients by gene expression microarray analysis of cancer samples and matched controls, and SNP arrays of germline DNA.

Results

8q24 (upstream ofMYC) and 18q21 (in the intron ofSMAD7), two of the loci most strongly linked with colorectal cancer risk, as well as 20q13 (in the intron ofLAMA5), are tightly associated with the prognosis of rectal cancer patients. For SNPs on 18q21 (rs12953717 and rs4464148) and 20q13 (rs4925386), alleles that correlate with higher risk for the development of colorectal cancer are associated with shorter disease free survival. However, for rs6983267 on 8q24, the low risk allele is associated with a higher risk for recurrence and metastasis after surgery, and importantly, is strongly correlated with the resistance of colorectal cancer cell lines to chemoradiotherapy. We also found that althoughMYCexpression is dramatically increased in cancer, patients with higher levels ofMYChave a better prognosis. The expression ofSMAD7is weakly correlated with disease free time. Notably, the presence of the 8q24 and 18q21 SNP alleles is not correlated with a change of expression ofMYCandSMAD7.rs4464148, and probably rs6983267 and rs4925386, are linked with overall survival time of patients.

Conclusions

SNPs at three colorectal cancer risk loci detect subpopulations of rectal cancer patients with poor prognosis. rs6983267 probably affects prognosis through interfering with the resistance of cancer cells to chemoradiotherapy.
Kinome rewiring reveals AURKA is a molecular barrier to the efficacy of PI3K/mTOR-pathway inhibitors in breast cancer
Authors: Donnella Hayley J , Webber James T , Levin Rebecca S , Camarda Roman , Momcilovic Olga , Bayani Nora , Korkola James , Shokat Kevan M , Goga Andrei , Gordan John , Bandyopadhyay Sourav
Published: July 2017

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest. We hypothesized that dynamic changes in signaling, including adaptation and feedback, limit drug efficacy. Using a quantitative chemoproteomics approach we mapped dynamic changes in the kinome in response to various agents and identified signaling changes that correlate with drug sensitivity. Measurement of dynamics across a panel of breast cancer cell lines identified that maintenance of CDK4 and AURKA activity was associated with drug resistance. We tested whether incomplete inhibition of CDK4 or AURKA was a source of therapy failure and found that inhibition of either was sufficient to sensitize most breast cancer cells to PI3K, AKT, and mTOR inhibitors. In particular, drug combinations including the AURKA inhibitor MLN8237 were highly synergistic and induced apoptosis through enhanced suppression of mTOR signaling to S6 and 4E-BP1 leading to tumor regressionin vivo.This signaling map identifies survival factors whose presence limits the efficacy of target therapy and indicates that Aurora kinase co-inhibition could unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer.
Movements and habitat use of the night parrot Pezoporus occidentalis in south‐western Queensland
Authors: Murphy Stephen A. , Silcock Jennifer , Murphy Rachel , Reid Julian , Austin Jeremy J.
Published: July 2017

The nocturnal, cryptic and geographically remote nature of night parrots, combined with their apparent rapid decline, means that very little is known of their biology or ecology. The discovery of a resident population in south‐western Queensland in 2013 provides the first opportunity to undertake detailed studies on this most enigmatic of birds. We attached a radio tag to a bird for 20 days in April 2015 and a GPS tag to another bird for 5 days in May 2016 to study movement patterns and habitat use. Both birds displayed similar behaviour but the GPS‐tagging provided a much finer resolution of spatial data. They called at dusk from their diurnal roosts amongst spinifex hummocks and then flew to more floristically diverse habitats dominated by large‐seeded species to feed. We conducted floristic surveys to describe the feeding grounds of the GPS‐tagged bird and make dietary inferences. This individual spent most of its time in highly diverse but ephemeral habitats, including seasonally inundated plains and depressions associated with the outer Diamantina floodplain and gilgais on ironstone plains. Prolifically seeding ephemeral species, most notably the annual grass Uranthoecium truncatum, dominate these feeding grounds. This work suggests that the habitat mosaic containing roost sites in close proximity to feeding grounds with key seed‐producing species is an important factor, rather than an association with spinifex or samphire alone. Further work is needed to examine movement patterns and habitat use in more typical dry seasons and the impact of cattle grazing on night parrot feeding areas, particularly with regard to seed production. The information presented here is vital for both in situ conservation of the Pullen‐Pullen‐Mt Windsor‐Diamantina population and for setting future research and survey priorities.
Accelerated growth of B16BL6 tumor in mice through efficient uptake of their own exosomes by B16BL6 cells
Authors: Matsumoto Akihiro , Takahashi Yuki , Nishikawa Makiya , Sano Kohei , Morishita Masaki , Charoenviriyakul Chonlada , Saji Hideo , Takakura Yoshinobu
Published: July 2017

Exosomes are extracellular vesicles released by various cell types and play roles in cell–cell communication. Several studies indicate that cancer cell‐derived exosomes play important pathophysiological roles in tumor progression. Biodistribution of cancer cell‐derived exosomes in tumor tissue is an important factor for determining their role in tumor proliferation; however, limited studies have assessed the biodistribution of exosomes in tumor tissues. In the present study, we examined the effect of cancer‐cell derived exosomes on tumor growth by analyzing their biodistribution. Murine melanoma B16BL6‐derived exosomes increased the proliferation and inhibited the apoptosis of B16BL6 cells, which was associated with an increase and decrease in the levels of proliferation‐ and apoptosis‐related proteins, respectively. GW4869‐induced inhibition of exosome secretion decreased the proliferation of B16BL6 cells, and treatment of GW4869‐treated cells with B16BL6‐derived exosomes restored their proliferation. Next, we treated B16BL6 tumors in mice with B16BL6‐derived exosomes and examined the biodistribution and cellular uptake of these exosomes. After the intratumoral injection of radiolabeled B16BL6‐derived exosomes, most radioactivity was detected within the tumor tissues of mice. Fractionation of cells present in the tumor tissue showed that fluorescently labeled exosomes were mainly taken up by B16BL6 cells. Moreover, intratumoral injection of B16BL6‐derived exosomes promoted tumor growth, whereas intratumoral injection of GW4869 suppressed tumor growth. These results indicate that B16BL6 cells secrete and take up their own exosomes to induce their proliferation and inhibit their apoptosis, which promotes tumor progression.
Pouch failures following ileal pouch–anal anastomosis for ulcerative colitis
Authors: Mark‐Christensen A. , Erichsen R. , Brandsborg S. , Pachler F. R. , Nørager C. B. , Johansen N. , Pachler J. H. , Thorlacius‐Ussing O. , Kjær M. D. , Qvist N. , Preisler L. , Hillingsø J. , Rosenberg J. , Laurberg S.
Published: July 2017

Aim

Ileal pouch–anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure.

Method

The study included 1991 patients with ulcerative colitis who underwent ileal pouch–anal anastomosis in Denmark in the period 1980–2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1–5 cases per year; low, 6–10; intermediate 11–20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis.

Results

Over a median 11.4 years, 295 failures occurred, corresponding to 5‐, 10‐ and 20‐year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10–1.75]. Primary non‐diversion (aHR 1.63, 95% CI 1.11–2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26–4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy.

Conclusion

In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch–anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non‐diversion were associated with a higher risk of pouch failure.
The effects of 2‐hydroxyethyl methacrylate on matrix metalloproteinases 2 and 9 in human pulp cells and odontoblast‐like cells in vitro
Authors: Sun S. , Wang G.‐l. , Huang Y. , Diwu H.‐l. , Luo Y.‐c. , Su J. , Xiao Y.‐h.
Published: July 2017

Aim

To assess the effects of 2‐hydroxyethyl methacrylate (HEMA) on proliferation and migration of human pulp cells, as well as on matrix metalloproteinase (MMP‐2 and MMP‐9) expression in human odontoblast‐like cells, contributing to the goal of determining the relationship between resin materials and MMP activity in pulp–dentine complexes.

Methodology

Dental pulp cell cultures were established from pulp tissue of human teeth extracted for orthodontic purposes. Pulp cell differentiation was characterized in the presence of dentine sialophosphoprotein, bone sialoprotein and alkaline phosphatase by reverse transcription polymerase chain reaction. MMP activity was assessed by gelatine zymography with media containing HEMA. Cell viability was evaluated using methyl thiazolyl tetrazolium assay for 24–72 h. Cell migration was tested using Transwell migration assay. Western blotting was used to visualize MMP expression with the nontoxic HEMA concentrations (0–400 μg mL−1) for 48 h.

Results

Pulp cell proliferation decreased with HEMA exposure in a time‐ and concentration‐dependent manner. HEMA concentrations ≤400 μg mL−1 did not induce changes in cell viability at 48 h (P < 0.05). Pulp cells were induced to differentiate into odontoblast‐like cells in media containing 5 mg mL−1 ascorbic acid and 10 mmol L−1 β‐sodium glycerophosphate for 3–4 weeks. After incubation with HEMA, dose‐dependent inhibition was observed; HEMA had a strong inhibitory effect on MMP activity. Compared with the control group, cell migration and MMP expression were inhibited significantly with increasing HEMA concentration at noncytotoxic doses (P < 0.05).

Conclusions

Cell viability was not affected at HEMA concentrations ≤400 μg mL−1. Within this range, HEMA inhibited MMP‐2 and MMP‐9 expression and activity, which may protect against type I collagen degradation effectively during dentine adhesive procedures.
Strengths of ceramic fiber bundles: Theory and practice
Authors: Callaway Evan B. , Zok Frank W.
Published: July 2017

The Weibull modulus and reference strength of ceramic fibers can be inferred from measurements of the tensile stress‐strain response of a bundle of such fibers. The goal of the present article is to address issues in the fidelity of results stemming from fiber bundle tests and strategies to optimize outcomes. The issues are addressed through established theorems in uncertainty propagation, Monte Carlo simulations of fiber bundle fracture, and experimental measurements on bundles of SiC fibers of various length and surface condition. The study shows that optimal results are obtained when: (i) tests are performed on fiber bundles with a gauge length that exceeds a critical value (specifically, that needed to prevent mechanical instabilities in the post‐load‐maximum domain); (ii) bundles are lubricated with a low‐viscosity oil, to mitigate both inter‐fiber friction and dynamic coupling associated with release waves following fiber fracture; and (iii) the Weibull parameters are obtained by directly fitting the measured stress‐strain curves with the function predicted by fiber bundle theory, rather than using methods based on either linear regression analysis of Weibull probability plots or fitting of the peak stress and strain alone.
Preparation and high‐temperature behavior of HfC–SiC nanocomposites derived from a non‐oxygen single‐source‐precursor
Authors: Cheng Jun , Wang Xiaozhou , Wang Hao , Shao Changwei , Wang Jun
Published: July 2017

A single‐source precursor for the preparation of HfC‐SiC ceramics was synthesized via a Grignard reaction using bis(cyclopentadienyl)hafnium(IV) dichloride, trans‐1,4‐dibromo‐2‐butene, and (chloromethyl)trimethylsilane as raw materials. The composition, structure, pyrolysis process and high‐temperature behavior of the precursor were investigated. The results show that the precursor with a backbone comprising Hf–C, Si–C and CH=CH groups exhibits good solubility in common solvents, such as tetrahydrofuran, dimethylbenzene, and chloroform. Pyrolysis of the precursor at 1000°C yielded a microcrystalline HfC phase with a ceramic yield of 63.86 wt%. The pyrolytic products at 1600°C were HfC–SiC nanocomposite ceramics, which exhibited good thermal stability up to 2400°C. The formation of a (Hf,Si)C solid‐solution would be beneficial for densification during the sintering process. The non‐oxygen structure, high ceramic yield, homogeneous composition and excellent high‐temperature behavior of the pyrolytic products make the as‐prepared precursor a promising material for the preparation of high‐performance ultra‐high‐temperature ceramics.
Review of phase III trial data on IL‐23 inhibitors tildrakizumab and guselkumab for psoriasis
Authors: Amin M. , Darji K. , No D.J. , Wu J.J.
Published: July 2017

The development of monoclonal antibodies targeting IL‐12 and IL‐23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL‐23 alone plays a role in the pathogenesis of psoriasis. The objective was to review the phase III clinical trial data for the anti‐IL‐23 agents to evaluate the safety and efficacy profile of each agent. We reviewed the results of the phase III clinical trials for the anti‐IL‐23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported. By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was >60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections. The anti‐IL‐23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL‐17 inhibitors with a favourable short‐term safety profile. The results of the phase III trials support the notion that IL‐23 is a potential target in psoriasis treatment.
Big Data Facilitation, Utilization, and Monetization: Exploring the 3Vs in a New Product Development Process
Authors: Johnson Jeff S. , Friend Scott B. , Lee Hannah S.
Published: July 2017

Big data is transforming the new product development (NPD) process. Organizations are investing heavily in big data capabilities to capitalize on the ongoing analytics movement. Yet there is a lack of understanding of how firms can leverage big data as a capability to generate innovation success in dynamic marketplaces. To address this need for improved insights, the authors operationalize and analyze the 3Vs of big data usage—volume, variety, and velocity—in an NPD model. Drawing on the results of a survey of 261 managers reporting on their business unit's NPD processes and big data usage, this study identifies the antecedents of the multidimensional usage of big data. Empirically assessing the effects of firm orientations, the authors show that an exploration orientation has a positive effect on all three dimensions of a firm's big data usage while an exploitation orientation has no effect. Moving downstream, the results also reveal that the environmental factor of customer turbulence interacts differentially with the big data usage dimensions' impact on new product revenue (NPR). Specifically, customer turbulence accentuates the relationship between big data velocity and NPR but attenuates the relationship between big data volume and NPR.
“What You See, Is What You Get?” Guidelines for Influencing Consumers' Perceptions of Consumer Durables through Product Appearance
Authors: Mugge Ruth , Dahl Darren W. , Schoormans Jan P. L.
Published: July 2017

Consumers often purchase consumer durables without using these products beforehand. Product appearance is then one of the factors that consumers use to form inferences about the experience and credence attributes of consumer durables. For companies, it is important to successfully manage these inference processes of consumers to create a competitive advantage. However, a comprehensive understanding of the relationships between product appearance and the inferences about products' experience and credence attributes is lacking. This research provides empirically based, generalizable guidelines to assist companies with selecting the product appearance of consumer durables to trigger strategically valued experience and credence attributes. An empirical analysis of 120 consumer durables, belonging to four product categories on 31 design characteristics identifies five design dimensions (i.e., harmony, novelty, natural, weight, compressed) that differentiate product appearances of consumer durables. Furthermore, the findings show that these design dimensions relate to perceptions of performance quality, ease of use, and technological advancement. Specifically, product appearances that score high on harmony, neutral on novelty, and somewhat above neutral on weight trigger the most positive performance quality perceptions. Product appearances that score high on natural, low on novelty, and neutral on compressed trigger the most positive ease of use perceptions. Novel and nonnatural appearances prompt positive inferences about technological advancement. These findings are integrated into a discussion of the managerial implications and the potential avenues for future research on product appearance.
Developing integrative systematics in the informatics and genomic era, and calling for a global Biodiversity Cyberbank
Authors: Wen Jun , Harris AJ , Ickert‐Bond Stefanie M. , Dikow Rebecca , Wurdack Kenneth , Zimmer Elizabeth A.
Published: July 2017

Systematics is the science of discovering, organizing and interpreting the diversity of all living organisms. Recent developments in genomics and biodiversity informatics are transforming systematics and have opened up many new opportunities. Major digitization efforts and developments in biodiversity informatics have helped the systematics community explore ways to enhance the efficiency in organizing, publishing, and utilizing systematic information. At the same time, genomics is rapidly facilitating construction of the tree of life, improving taxonomic classification, and disentangling complex evolutionary histories. In the informatics and genomics era, systematics has an incredible capacity to integrate with computational and exploratory platforms for discovery as well as with other, related disciplines while maintaining its core strengths in biological collections and morphology. We call for the establishment of a new global cyberinfrastructure or Biodiversity Cyberbank that will function as the main repository of many types of biodiversity data to ensure the long‐term sustainability of the vast and growing amount of systematic data. This Biodiversity Cyberbank will contain new and efficient analytical pipelines for systematics research, especially for efficiently generating taxonomic treatments (revisions, e‐monographs and floras). Integrative systematics requires the training of the next‐generation systematists with taxonomic, phylogenomic and informatics skills to address grand questions about biodiversity and its assembly and continue to develop the Biodiversity Cyberbank. Integrative systematics must also proactively educate the public and policy makers on the importance of systematics and collections for addressing the biodiversity crisis of the Anthropocene, and a Biodiversity Cyberbank may represent one powerful tool for outreach.
When new human‐modified habitats favour the expansion of an amphibian pioneer species: Evolutionary history of the natterjack toad (Bufo calamita) in a coal basin
Authors: Faucher Leslie , Hénocq Laura , Vanappelghem Cédric , Rondel Stéphanie , Quevillart Robin , Gallina Sophie , Godé Cécile , Jaquiéry Julie , Arnaud Jean‐François
Published: July 2017

Human activities affect microevolutionary dynamics by inducing environmental changes. In particular, land cover conversion and loss of native habitats decrease genetic diversity and jeopardize the adaptive ability of populations. Nonetheless, new anthropogenic habitats can also promote the successful establishment of emblematic pioneer species. We investigated this issue by examining the population genetic features and evolutionary history of the natterjack toad (Bufo [Epidalea] calamita) in northern France, where populations can be found in native coastal habitats and coalfield habitats shaped by European industrial history, along with an additional set of European populations located outside this focal area. We predicted contrasting patterns of genetic structure, with newly settled coalfield populations departing from migration–drift equilibrium. As expected, coalfield populations showed a mosaic of genetically divergent populations with short‐range patterns of gene flow, and native coastal populations indicated an equilibrium state with an isolation‐by‐distance pattern suggestive of postglacial range expansion. However, coalfield populations exhibited (i) high levels of genetic diversity, (ii) no evidence of local inbreeding or reduced effective population size and (iii) multiple maternal mitochondrial lineages, a genetic footprint depicting independent colonization events. Furthermore, approximate Bayesian computations suggested several evolutionary trajectories from ancient isolation in glacial refugia during the Pleistocene, with biogeographical signatures of recent expansion probably confounded by human‐mediated mixing of different lineages. From an evolutionary and conservation perspective, this study highlights the ecological value of industrial areas, provided that ongoing regional gene flow is ensured within the existing lineage boundaries.
Human umbilical cord‐derived mesenchymal stem cells conditioned medium attenuate interstitial fibrosis and stimulate the repair of tubular epithelial cells in an irreversible model of unilateral ureteral obstruction
Authors: Liu Bo , Ding Feng‐Xia , Liu Yang , Xiong Geng , Lin Tao , He Da‐Wei , Zhang Yuan‐Yuan , Zhang De‐Ying , Wei Guang‐Hui
Published: July 2017

Aim

The growing number of patients suffering from chronic renal disease (CKD) is a challenge for the development of innovative therapies. Researchers have studied the therapeutic effects of cell therapy in acute kidney injury (AKI). However, the therapeutic effect of conditional medium (CM) in the CKD models have been rarely reported. Here, we examined the effects of umbilical cord derived‐mesenchymal stem cells (hUC‐MSCs) CM on renal fibrosis in a rat model of unilateral ureteral obstruction (UUO).

Methods

Animals were randomly divided into three groups: sham‐operated, UUO, UUO + CM. CM was administered via the left renal artery after total ligation of the left ureter. Rats were killed after 14 days of obstruction. Histological changes and oxidative stress parameters were assessed. Western blotting and immunohistochemistry analysis were used to measure epithelial‐mesenchymal transition (EMT) markers, including epithelial cadherin (E‐cadherin), α‐smooth muscle actin (α‐SMA), tumour necrosis factor‐α (TNF‐α), Collagen‐I, and transforming growth factor β1 (TGF‐β1). Proliferation and apoptosis of renal tubular epithelial cells (RTEs) were also measured.

Results

HucMSC‐CM significantly reduced the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and increased the activity of glutathione (GSH) induced by UUO. Moreover, CM significantly reduced the expression of TGF‐β1, α‐SMA, TNF‐α and Collagen‐I in UUO kidney, promoted the proliferation of RTEs and inhibited its apoptosis. In addition, the increased expression of E‐cadherin also reflects the effective improvement of renal interstitial fibrosis.

Conclusion

This study shows that CM protects UUO‐induced kidney damage and therefore could be a potential tool to prevent CKD progression.
Solanum dulcamara's response to eggs of an insect herbivore comprises ovicidal hydrogen peroxide production
Authors: Geuss Daniel , Stelzer Sandra , Lortzing Tobias , Steppuhn Anke
Published: July 2017

Plants can respond to insect oviposition, but little is known about which responses directly target the insect eggs and how. Here, we reveal a mechanism by which the bittersweet nightshade Solanum dulcamara kills the eggs of a generalist noctuid herbivore. The plant responded at the site of oviposition by Spodoptera exigua with formation of neoplasms and chlorotic tissue, accumulation of reactive oxygen species and induction of defence genes and proteins. Transcriptome analysis revealed that these responses were reflected in the transcriptional reprogramming of the egg‐laden leaf. The plant‐mediated egg mortality on S. dulcamara was not present on a genotype lacking chlorotic leaf tissue at the oviposition sites on which the eggs are exposed to less hydrogen peroxide. As exposure to hydrogen peroxide increased egg mortality, while catalase supplementation prevented the plants from killing the eggs, our results suggest that reactive oxygen species formation directly acts as an ovicidal plant response of S. dulcamara.
Dedifferentiated carcinoma with clear cell carcinoma of the endometrium: A case report
Authors: Lee Seung Eun , Park Ha young , Shim Seung‐Hyuk , Kim Wook Youn
Published: July 2017

Endometrial dedifferentiated carcinoma consists of a combination of undifferentiated and differentiated carcinomas. To date, clear cell carcinoma components in endometrial dedifferentiated carcinoma have not been reported. We report the first case of endometrial dedifferentiated carcinoma with clear cell carcinoma in a 58‐year‐old woman. The uterine corpus was completely replaced and enlarged by a heterogeneous mass. The endometrial cut surface showed a yellowish papillary growing mass involving endometrium and deeper myometrium. Microscopically, the three components (endometrioid carcinoma, FIGO grade 1, clear cell carcinoma and undifferentiated carcinoma) were noted with differentiated carcinoma components lining the endometrial cavity, while undifferentiated carcinoma components were identified in deeper endometrium and myometrium. Our histologic diagnosis was supported by the pattern of immunoreactivity. Tumor cells showed loss of expression of MLH1/PMS2 protein and displayed high microsatellite‐instability in all three components. Furthermore, all three components including clear cell carcinoma had loss of PTEN and ARID1A expression. Our observations suggest that the three components derived from a monoclonal origin, as the three components had in common specific genetic alterations.
Sympathetic and parasympathetic cardiac responses to phobia‐relevant and disgust‐specific emotion provocation in blood‐injection‐injury phobia with and without fainting history
Authors: Simon Erica , Meuret Alicia E. , Ritz Thomas
Published: July 2017

The autonomic regulation in blood‐injection‐injury (BII) phobia has received particular attention due to the unique link between fear and fainting in this anxiety disorder. However, systematic exploration of sympathetic and parasympathetic cardiac activity during exposure to phobia‐relevant emotional stimuli has remained rare and inconclusive, including with regard to disgust, a frequent response to BII stimuli. Existing studies using respiratory sinus arrhythmia (RSA) as a noninvasive index of parasympathetic cardiac activity also have not accounted sufficiently for effects of respiration. We compared 60 participants with BII phobia (27 with and 33 without history of loss of consciousness) and 20 healthy controls during emotion induction with films, including a disgust and a BII‐relevant surgery film. Cardiorespiratory activity was measured continuously, with RSA (controlled for respiration) and T‐wave amplitude (TWA; as a noninvasive index of sympathetic cardiac activity) extracted. Significant increases in RSA during the surgery film were observed for participants with a history of loss of consciousness compared to others, but controlling for respiration eliminated these differences. Sympathetic effects with heart rate accelerations, which were most pronounced for the disgust film, did not differentiate groups. However, substantial increases in RSA and TWA, suggesting parasympathetic excitation and sympathetic withdrawal, were observed in five participants that became presyncopal during the surgery film. Thus, parasympathetic excitation and sympathetic withdrawal appear to be cardinal autonomic features in BII phobia, but larger studies of participants reaching presyncopal states in BII‐relevant stimulus exposure are needed to consolidate these findings.
Resting heart rate, guilt, and sympathy: A developmental psychophysiological study of physical aggression
Authors: Colasante Tyler , Malti Tina
Published: July 2017

Although low resting heart rate has been linked to frequent aggressive conduct in childhood, little is known about the interaction of this biological risk with social emotions that protect against aggression across development. With a sample of 5‐, 8‐, and 12‐year‐olds (N = 110), we tested whether the negative link between resting heart rate and physical aggression was offset by high guilt and sympathy. Caregivers reported their children's physical aggression and sympathy. Children's electrocardiogram data were collected while they viewed a nondescript video, after which they reported their guilt—or lack thereof—in response to vignettes depicting social transgressions. Lower resting heart rate was significantly associated with higher physical aggression in 5‐year‐olds who reported low—but not medium and high—levels of guilt, and in 8‐year‐olds with low—but not medium and high—ratings of sympathy. Neither guilt nor sympathy moderated the resting heart rate–physical aggression link in 12‐year‐olds. We discuss how social emotions may help children with low resting heart rates navigate social conflicts and avoid aggressive physical confrontations.