bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect and mechanism of lentivirus‐mediated silencing of TPX2 gene on proliferation and apoptosis of human hepatoma cells
Authors: Ding Lei , Zhang Shuhong , Chen Shijun , Zheng Lixue , Xiao Lianxiang
Published: December 2018

This study aimed to investigate the role and mechanism of action of targeting protein for Xklp2 (TPX2) in liver cancer, we compared TPX messenger RNA (mRNA) expression in liver cancer tissue samples and adjacent normal liver tissue samples as well as in human liver cancer cell lines and nonmalignant cell line by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). TPX2 gene was silenced in HepG2 cells by transfection with the lentiviral vector expressing TPX2‐targeting short hairpin RNA (shRNA), and the knockdown efficiency was evaluated by RT‐qPCR. Cell proliferation, apoptosis as well as protein level of c‐Myc, cyclin D1, caspase‐3, phosphorylated glycogen synthase kinase‐3β (p‐GSK‐3β), and β‐catenin in HepG2 cells were evaluated before and after the TPX2 knockdown. Wnt/β‐catenin signaling pathway was inhibited by treatment with 20 μM of XAV‐939 or activated by treatment with 20 mM of LiCl. We found that TPX2 mRNA level was significantly increased in liver cancer tissue samples and cell lines comparing to noncancerous counterparts (P < 0.05). TPX2 knockdown significantly reduces TPX2 expression (P < 0.01), cell proliferation (P < 0.05), protein level of c‐Myc and cyclin D1 (P < 0.01), activation of Wnt/β‐catenin signaling in HepG2 cells (P < 0.01) while increasing cell apoptosis (P < 0.01). Treatment with XAV‐939 significantly reduced HepG2 cell proliferation (P < 0.05) while increasing cell apoptosis (P < 0.01). Treatment with LiCl significantly attenuated the antiproliferative and apoptosis‐promoting effect of TPX2 knockdown on HepG2 cells (P < 0.05). Lentivirus‐mediated silencing of TPX2 gene could inhibit proliferation and induce apoptosis in hepatoma cells by inhibiting Wnt signaling pathway and regulating cyclin and apoptosis‐related proteins.
Breast cancer‐linked lncRNA u‐Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding
Authors: Mansoori Yaser , Zendehbad Zahra , Askari Alireza , Kouhpayeh Amin , Tavakkoly‐Bazzaz Javad , Nariman‐Saleh‐Fam Ziba , Bastami Milad , Saadatian Zahra , Mansoori Behnam , Yousefvand Amin , Mansoori Hosein , Daraei Abdolreza
Published: December 2018

Recently, it has been revealed that estrogen‐related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen‐related long noncoding RNAs (lncRNAs) upstream Eleanor (u‐Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer‐free women who had undergone cosmetic mammoplasty. The expression levels of u‐Eleanor and HOTAIR were measured using quantitative real‐time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high‐level expression of u‐Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months (P = 0.03) as well as the women with a breastfeeding duration of more than 24 months (P = 0.005). Furthermore, a higher expression of u‐Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months (P = 0.02). In the same way, the results of correlation test (r = −0.258; P = 0.036) and multivariate regression model (β = −0.321; P = 0.023) are indicative of a significant relationship of elevated expression of u‐Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.
MicroRNA‐7b attenuates ischemia/reperfusion‐induced H9C2 cardiomyocyte apoptosis via the hypoxia inducible factor‐1/p‐p38 pathway
Authors: Sheng Zulong , Lu Wenbin , Zuo Zhi , Wang Dong , Zuo Pengfei , YAO Yuyu , Ma Genshan
Published: December 2018

Objective

MicroRNAs (miRNAs) have been shown to play crucial roles in the occurrence, development, and treatment of many cardiovascular diseases. Coronary heart disease (CAD)‐related miRNAs are still a growing research area. miR‐7b was reported to be downregulated in acute myocardial infarction (AMI) myocardium tissues. However, it remains largely unknown whether miR‐7b is involved in the pathogenesis and progression of the AMI ischemia/reperfusion (I/R) injury.

Methods

Male C57BL/6 J mice and H9C2 cells were used as models in this study. Masson staining, real‐time polymerase chain reaction, Western blot analysis, and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end‐labeling immunofluorescence staining assays were performed to detect the related indicators in the study. SPSS 17.0 software was used to calculate the experimental data.

Results

The results showed that miR‐7b expression is downregulated after I/R in mice, and miR‐7b could inhibit apoptosis in I/R‐induced H9C2 cells via upregulating hypoxia‐inducible factor 1a (HIF1a). The inhibitory effect of miR‐7b on I/R‐induced apoptosis in H9C2 cells was blocked by HIF1a silencing. In addition, our data suggested that the p‐P38 pathway may be involved in the role of miR‐7 in I/R‐induced H9C2 cell apoptosis.

Conclusion

We confirmed that the overexpression of miR‐7b inhibits I/R‐induced apoptosis in H9C2 cells by targeting the HIF1a/p‐P38 pathway. Our findings not only demonstrate the potential role of miR‐7b in attenuating I/R‐induced apoptosis but also provide a new insight into the better prevention of the I/R injury by mediating HIF‐1 and p‐P38.
The inhibitory effects of Qingchang Wenzhong granule on the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium‐induced colitis
Authors: Shi Lei , Dai Yi , Jia Boyi , Han Yafei , Guo Yi , Xie Tianhong , Liu Jiali , Tan Xiang , Ding Panghua , Li Junxiang
Published: December 2018

Background

Ulcerative colitis (UC) is a kind of complex immune disease, the pathogenesis of which remains elusive. Destruction of the intestinal barrier, extreme inflammation, oxidative stress, and apoptosis might play key roles in the development of UC. In previous studies, we observed that Qingchang Wenzhong granule (QCWZG) had the exact effect on the remission of UC in the clinic; however, the underlying mechanism has not been identified. This study aimed to reveal the effects of QCWZG on the intestinal physical barrier and the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium (DSS)–induced colitis.

Methods

Sixty rats were randomly divided into six groups: blank group, model group, high/mild/low‐dose QCWZG groups, and mesalazine group. The rats in the experimental group drank 4% DSS for 7 days and 1% DSS for the subsequent 7 days. Different medications or distilled water was supplied by intragastric administration for 7 days. The levels of colitis and indices related to inflammation, oxidative stress, and apoptosis were assessed.

Results

Compared with the model group, the QCWZG group (P < 0.05) demonstrated attenuated disease activity index, colonic mucosa disease index, histological lesions, and colonic weights; lower levels of inflammatory substances, such as interleukin (IL)‐1α, IL‐6, tumor necrosis factor‐α, and myeloperoxidase; lower levels of malondialdehyde; and increased levels of superoxide dismutase and glutathione peroxidase. The QCWZG group also demonstrated elevated expression of Bcl‐2 and occluding but downregulated db expression of Bax and caspase 3 in the colon.

Conclusion

QCWZG could relieve rats with DSS‐induced colitis from UC symptoms by improving the intestinal physical barrier, which resists the interactive network of inflammation, oxidative stress, apoptosis, and their overactivated interactions.
Repeatability and reproducibility of variable flip angle T1 quantification in the prostate at 3 T
Authors: Zhong Xinran , Shakeri Sepideh , Liu Dapeng , Sayre James , Raman Steven S. , Wu Holden H. , Sung Kyunghyun
Published: December 2018

Background

Variable flip angle (VFA) imaging is widely used for the estimation of T1 relaxation in the prostate, but may have limited repeatability and reproducibility due to its sensitivity to B1+ inhomogeneity.

Purpose

To assess the repeatability and reproducibility of prostate T1 estimation with and without compensating for B1+ variation.

Study Type

Prospective.

Population

Twenty‐one volunteers were prospectively recruited and scanned twice on two 3 T MRI scanners, resulting in 84 VFA T1 exams.

Field Strength/Sequence

3 T/2D saturated turbo fast low angle shot (FLASH) and 3D dual‐echo FLASH.

Assessment

Two B1+ mapping techniques, including reference region VFA (RR‐VFA) and saturated turbo FLASH (satTFL), were used for B1+ correction, and T1 maps with and without B1+ correction were tested for intrascanner repeatability and interscanner reproducibility. Volumetric regions of interest (ROIs) were drawn on the transition zone, peripheral zone of the prostate, and the obturator internus left and right muscles in the corresponding slices.

Statistical Tests

The average T1 within each ROI for each scan was compared for both intra‐ and interscanner variability using concordance correlation coefficient and a Bland–Altman plot.

Results

Both RR‐VFA‐corrected T1 and satTFL‐corrected T1 showed higher intra‐ and interscanner correlation (0.89/0.87 and 0.87/0.84, respectively) than VFA T1 (0.84 and 0.74). Bland–Altman plots showed that VFA T1 had wider 95% limits of agreement and a larger range of T1 for each tissue compared with T1 with B1+ correction.

Data Conclusion

The application of B1+ correction (both RR‐VFA and satTFL) to VFA T1 results in more repeatable and reproducible T1 estimation than VFA T1. This can potentially provide improved quantification of the prostate dynamic contrast‐enhanced MRI parameters.

Level of Evidence 1.

Technical Efficacy Stage 1.

J. Magn. Reson. Imaging 2018.
Identification of ampullary carcinoma mixed subtype using a panel of six antibodies and its clinical significance
Authors: Liu Fangfang , Shen Danhua , Ma Yingteng , Song Qiujing , Wang Hanlin
Published: December 2018

Objectives

To investigate the function of immunomarkers CK7, CK20, CK17, CDX2, MUC1, and MUC2 in the identification of primary ampullary carcinoma mixed subtype.

Methods

Forty‐two cases of primary ampullary carcinoma were performed by immunohistochemical studies. The correlation between the mixed subtype and the other two subtypes and patient survival data was analyzed using the SPSS 16.0 statistical software.

Results

Among 42 cases, 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns: 91.7% (11/12) for CK7, 83.3% (10/12) for CK20; 66.7% (8/12) for CK17, CDX2, and MUC1; and 50% (6/12) for MUC2. Ten (83.3%) mixed types coexpressed four or more immunomarkers. Eight (19%) intestinal subtypes mainly showed a positive expression of CK20, CDX2, and MUC2. Twenty‐two (52.4%) pancreaticobiliary subtypes showed a positive expression of CK7, MUC1, and CK17. Stages III and IV diseases in mixed subtype (25%) and intestinal subtype (25%) were less than pancreaticobiliary subtype(63.6%) (p = 0.039). Follow‐up data appeared to show a better survival rate for patients with mixed subtype than those with pancreaticobiliary subtypes.

Conclusion

Immunohistochemical staining provided a more reliable means of diagnosing mixed ampulla carcinoma. Accurate subtyping of ampullary carcinoma is clinically important to select effective chemotherapy regimens and to assess disease prognosis.
Effects of game‐product congruity on in‐app interstitial advertising and the moderation of media‐context factors
Authors: Wang Shaojung Sharon , Chou Hsuan‐Yi
Published: December 2018

Advertising has become one of the major sources of game apps revenues and interstitial ads, in particular, are the most used monetization method among the types of in‐game mobile ad formats. Interstitial ads overlaid on top of a mobile game app have more obvious advertising intent and a higher degree of forced exposure and perceived intrusiveness. This study examined how the degree of congruity (high vs. moderate vs. low) between the promoted products in interstitial ads and the mobile game app environment affects consumers’ responses. The moderating effects of media‐context factors (i.e., excited– or calm–happiness game types and game immersion) were further assessed. The results of two experiments revealed that game‐product congruity lead to better consumers’ responses toward ads and advertised products. The positive effects of game‐product congruity were more salient when consumers played calm–happiness games and were less immersed in the game. Theoretical implications on integrating perspectives across disciplines such as schema theory, happiness, and immersion within the media‐context framework, as well as practical suggestions are discussed.
Identification of a de novo splicing variant in the Coffin–Siris gene, SMARCE1, in a patient with Angelman‐like syndrome
Authors: Aguilera Cinthia , Gabau Elisabeth , Laurie Steve , Baena Neus , Derdak Sophia , Capdevila Núria , Ramirez Ariadna , Delgadillo Veronica , García‐Catalan Maria Jesus , Brun Carme , Guitart Miriam , Ruiz Anna
Published: December 2018

Background

Patients affected by Angelman syndrome (AS) present severe intellectual disability, lack of speech, ataxia, seizures, abnormal electroencephalography (EEG), and a characteristic behavioral phenotype. Around 10% of patients with a clinical diagnosis of AS (AS‐like) do not have an identifiable molecular defect. Some of these patients harbor alternative genetic defects that present overlapping features with AS.

Methods

Trio whole‐exome sequence was performed on patient and parent's DNA extracted from peripheral blood. Exome data were filtered according to a de novo autosomal dominant inheritance. cDNA analysis was carried out to assess the effect of the splice site variant.

Results

We identified a novel heterozygous SMARCE1 splicing variant that leads to an exon skipping in a patient with an Angelman‐like phenotype. Missense variants in the SMARCE1 gene are known to cause Coffin–Siris syndrome (CSS), which is a rare congenital syndrome. Clinical reevaluation of the patient confirmed the presence of characteristic clinical features of CSS, many of them overlapping with AS.

Conclusions

Taking into account the novel finding reported in this study, we consider that CSS should be added to the expanding list of differential diagnoses for AS.
Identification of ANLN as a new likely pathogenic gene of branchio‐otic syndrome in a three‐generation Chinese family
Authors: Deng Lisha , Liu Yuanzhen , Xia Wenjun , Hu Jiongjiong , Ma Zhaoxin
Published: December 2018

Background

Branchio‐oto‐renal (BOR) syndrome is one of the most common autosomal dominant hearing loss syndromes and features clinical and genetic heterogeneity. When there is no renal deformity, this disease can also be called branchio‐otic (BO) syndrome. Though many genes have been reported, there are still many BO syndrome‐related genes to be identified. To identify a hitherto unknown candidate gene causing BO syndrome in a three‐generation Chinese family, clinical, genetic, and functional analyses were employed.

Methods

Whole‐exome sequencing (WES) was conducted in three affected family members and two unaffected family members. PCR‐Sanger sequencing was performed in all of the family members for segregation analysis and verification of the candidate variants. PCR‐Sanger sequencing was also employed in 150 healthy people to examine the variants. In silico analysis was used to predict possible changes in the protein structure that may affect the phenotype.

Results

We identified a heterozygous missense variant in ANLN: NM_018685.4: c.G1105A; NP_061155.2: p.G369R that segregated in the pedigree with an autosomal dominant pattern. No variant was found in the 150 controls and normal family members at this site. The variant c.G1105A was located in a highly conserved F‐actin binding site. The amino acid residue at position 369 in the ANLN protein was highly conserved across different species.

Conclusion

In this study, we identified, for the first time, a heterozygous missense variant in ANLN (NM_018685.4: c.G1105A; NP_061155.2: p.G369R) that is likely to be a candidate causative gene of BO syndrome in a specific Chinese family.
Comparison of a low‐cost magneto‐inductive magnetometer with a proton magnetometer: a case study on the Galali iron ore deposit in western Iran
Authors: Shahsavani Hashem
Published: December 2018

The proton magnetometers, also known as the proton precession magnetometers, are among the most widely used instruments for magnetometry surveys, owing to their high resolution which is about 0.01 nT. As the economically attractive ferromagnetic deposits generate a magnetic field anomaly which exceeds 100 nT, this resolution is not needed for detecting such large signals. The recently introduced magneto‐inductive technology has led to the development of a low‐cost magnetometer that can measure the ground magnetic field up to a resolution of around 10 nT. These magnetometers are inexpensive, come in a very small size, and are lightweight compared to the more common magnetometers such as the proton precession type. In this research, a low‐cost magneto‐inductive sensor and a highly precise proton magnetometer are simultaneously utilized at the same profiles on the Galali iron ore deposit in the northwest of Iran. The discrepancy of two measurements is less than 400 nT, often less than 100 nT, while the changes in the total magnetic field on this anomaly are around 7500 nT, which is 11 times larger than the maximum difference between the two measurements. In addition, the value of the regression coefficient between the two measurements for all profiles is more than 0.97. Also, the slope of the fitted line for the two measurements for all profiles is close to one. These results demonstrate the applicability of the new low‐cost magneto‐inductive sensor in magnetic prospecting.
Collisions: Negotiating tensions in a shared marketplace
Authors: Pryor Susie , Adkins Natalie Ross
Published: December 2018

Nonprofit organizations (NPOs) operate within marketing systems comprising broader networks of individuals, groups, and/or entities linked through shared participation in economic exchanges. These systems include diverse constituents with varied goals and orientations. Inherently, tensions arise as NPOs, for‐profit firms, and other social actors pursue differing agendas, often competing for finite resources. In this paper, we report the results of an ethnographic study, which examines one community's efforts to alleviate these tensions as they occur in a downtown business district. The area is noted for its economic vitality and diversity, but struggles to accommodate the needs of the homeless population and the social service agencies who maintain a presence there. Relationships between multiple constituencies erode as the business community seeks to displace both the social service agencies and the individuals they serve. The community in this study moved through thematic stages of problem solving associated with contentious social issues. They sought to use a bridging organization by forming a local homeless task force. An apparent breakdown occurred when the task force was unable to articulate integrative values and a vision for the community as a whole. The study illustrates the importance of establishing a set of shared values and vision and emphasizes the importance of the establishment of bridging organizations with power and authority to negotiate and implement changes. It challenges the utilization of sociospatial and relational mechanisms, which are designed to physically shift the homeless from the area.
Health disparities: Using policies to rethink our strategies for eliminating the impact of food deserts by focusing on unhealthy dietary patterns
Authors: Wallace Edward V.
Published: December 2018

For years, we have been interested in understanding the relationship between dietary patterns and diseases, and most recently, we have put efforts toward analyzing the impact of food deserts as they relate to dietary patterns. Unhealthy eating has become an epidemic in low‐income neighborhoods that are considered to be food deserts due to the fact that people are not meeting their recommended daily intake of nutritionally dense foods. Adults should be consuming at least 20 to 35 g of fiber daily, however, many Americans only consume 12 to 17 g of fiber daily at best. Furthermore, as a society, we Americans consume way too much added sugar, saturated fat, and salt. Although there are a number of reasons that unhealthy dietary patterns exist in our society especially in low‐income communities, it is important that we pay particular attention to how food deserts have developed and how they are major contributors to the overall poor health of low‐income Americans. Therefore, the purpose of this is paper is to encourage its audience to rethink how we can implement policies to address the issue of unhealthy dietary patterns by reducing or eliminating food deserts. Specifically, we explore the effect of implementing evidence‐based policies such as nutrition initiatives, corner store initiatives, menu labeling, food assistance programs, and the punitive taxation of sugary beverages and unhealthy foods similar to the punitive taxes placed on tobacco.
Discovery and characterisation of lycorine‐type alkaloids in Lycoris spp. (Amaryllidaceae) using UHPLC‐QTOF‐MS
Authors: Li Aiqian , Du Zhifeng , Liao Mei , Feng Yulin , Ruan Hanli , Jiang Hongliang
Published: December 2018

Introduction

Lycorine, one of the most common alkaloids in Lycoris spp., is believed to possess pharmacological activity.

Objective

To discover and identify lycorine‐type alkaloids in the crude extracts of bulbs from six Lycoris spp. by ultra‐high‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) detection.

Methodology

A qualitative analytical method with a data mining strategy was utilised. Based on the fragmentation patterns of standards investigated in positive tandem mass spectrometry (MS/MS) mode, the fragmentation rules of lycorine‐type alkaloids were summarised. These types of alkaloids were additionally classified as different subtypes based on structural features and MS/MS fragmentation patterns, and the diagnostic ions for characterisation of different subtypes of alkaloids were designated.

Results

Thirty‐seven lycorine type alkaloids, including 16 previously undescribed compounds, were efficiently screened out and tentatively identified from the crude extracts of six Lycoris spp. Lycoris sprengri may be a preferable species for studying or extracting lycorine‐type alkaloids because of elevated relative concentrations and highest diversity of alkaloids.

Conclusion

The UHPLC‐QTOF‐MS and MS/MS data‐mining strategy proved useful for the detection and tentative identification of lycorine‐type alkaloids in bulbs of Lycoris spp. and could be extended to other Amaryllidaceae genera. The consequent profiling of the lycorine‐type alkaloids will be useful in the quality control of raw materials of Lycoris species and the exploration of superior species.
Effects of personality traits and social status on academic achievement: Gender differences
Authors: Janošević Marko , Petrović Boban
Published: December 2018

This study investigates the contribution of personality traits (HEXACO traits and Schizotypy) and social status dimensions (sociometric and perceived popularity) in understanding boys’ and girls’ respective academic achievement. The sample included 163 elementary school students from Serbia, aged 14–15 (87 girls and 76 boys). Regression analysis reveals that personality traits explain a similar amount of academic achievement variance in two gender groups (22% vs. 20% in girls’ favor), but social status proves to be a better predictor of academic achievement for boys (27% vs. 4% in boys’ favor). High Conscientiousness, perceived popularity as well as low extraversion turned out to be related to girls’ academic achievement. Low Schizotypy and Honesty‐Humility, as well as high openness, sociometric, and perceived popularity turned out to be related to boys’ academic achievement. Conscientiousness appears not to be related to boys’ academic achievement. The results are discussed and recommendations for improving educational practices are offered.
Implications of Goods and Services Tax reform on the Make in India initiative: A system dynamics perspective
Authors: Ojha Ravindra , Vrat Prem
Published: December 2018

The paper highlights the implications of Goods and Services Tax (GST), a major tax reform in India launched in July 2017 on the Make in India initiative launched in the year 2014. The GST is expected to trigger its impact on the following eight elements: warehouse efficiency, interstate check‐post operations, informal to formal business transition, interstate business expansion by micro, small, and medium enterprises, simplicity and transparency in tax collection process, logistics cost reductions, ease of doing business in India, and working capital cost realignment, which in turn may accelerate the manufacturing growth in Indian economy. In order to study the impact of the factors of GST on the Make in India initiative and the manufacturing growth, a system dynamics approach has been adopted in this paper. A number of simulation runs carried out using the system dynamics modelling have provided meaningful insights to the policymakers and strategic planners for evolving strategies for manufacturing growth.
Canine non‐epitheliotropic CD4‐positive cutaneous T‐cell lymphoma: a case report
Authors: Kondo Hitoshi , Kagawa Yumiko , Shirota Kinji , Moore Peter F. , Nagata Masahiko
Published: December 2018

A 5‐year‐old, spayed female French Bulldog presented with multiple papules on the skin of the scapular area. Histopathological examination of punch biopsy samples revealed dense infiltration of small lymphoid cells in the superficial dermis and in areas surrounding hair follicles. Immunohistochemical analysis indicated that these cells were positive for CD3, CD4, and TCRαβ, but negative for CD1c, CD8α, CD8β, CD11c, CD20, CD45RA, CD90, MHC‐II, and TCRγδ. In addition, CD45 was highly expressed, and the proliferation fraction was very low. Molecular clonality of T‐cell receptor G chains yielded a clonal result. The skin lesions were surgically excised because they had progressed to the lateral front leg. Postoperative clinical course was favorable, and recurrence was not observed until the dog died in a traffic accident, approximately 1 year later.
A model for cellular mechanotransduction and contractility at finite strain
Authors: Bouklas N. , Sakar M. S. , Curtin W. A.
Published: December 2018

The article from this special issue was previously published in ZAMM ‐ Journal of Applied Mathematics and Mechanics / Zeitschrift für Angewandte Mathematik und Mechanik, Volume 98, Issue 10, 2018. For completeness we are including the title page of the article. The full text of the article can be read in Issue 98:10 on Wiley Online Library: https://onlinelibrary.wiley.com/doi/full/10.1002/zamm.201700368
The Neuroscience of Creativity
Authors: Abraham Anna
Published: December 2018

What happens in our brains when we compose a melody, write a poem, paint a picture, or choreograph a dance sequence? How is this different from what occurs in the brain when we generate a new theory or a scientific hypothesis? In this book, Anna Abraham reveals how the tools of neuroscience can be employed to uncover the answers to these and other vital questions. She explores the intricate workings of our creative minds to explain what happens in our brains when we operate in a creative mode versus an uncreative mode. The vast and complex field that is the neuroscience of creativity is disentangled and described in an accessible manner, balancing what is known so far with critical issues that are as yet unresolved. Clear guidelines are also provided for researchers who pursue the big questions in their bid to discover the creative mind.
Leading Congress Member Promises Renewed Focus on Climate Change
Authors: Showstack Randy
Published: December 2018

In a statement issued at AGU’s Fall Meeting 2018, House Science Committee ranking member Rep. Eddie Bernice Johnson says that “it is time to stand up for science.”
Variations in Seismogenic Thickness Along the Central Alpine Fault, New Zealand, Revealed by a Decade's Relocated Microseismicity
Authors: Michailos Konstantinos , Smith Euan G.C. , Chamberlain Calum J. , Savage Martha K. , Townend John
Published: December 2018

The Alpine Fault is an oblique strike‐slip fault that is known to fail in large magnitude (M7–8) earthquakes, yet it is currently seismically quiescent. We examine the low‐magnitude earthquake activity occurring along the central portion of the Alpine Fault using seismic data from five temporary seismic networks deployed for various lengths of time between late 2008 and early 2017. Starting from continuous seismic data, we detect earthquake arrivals and construct the longest and most extensive microearthquake catalog for the central Alpine Fault region to date, containing 9,111 earthquakes. This enables us to study the distribution and characteristics of the seismicity in unprecedented detail. Earthquake locations are constrained by high‐quality automatic and manual picks, and we perform relocations using waveform cross‐correlation to better constrain hypocenters. We have derived a new local magnitude scale calibrated by Mw values. Magnitudes range between ML−1.2 and 4.6, and our catalog is complete above ML 1.1. Earthquakes mainly occur southeast of the Alpine Fault (in the hanging wall) and exhibit low magnitudes. We observe a lack of seismicity beneath Aoraki/Mount Cook, which we associate with high uplift rates and high heat flow. Seismogenic cutoff depths vary along the strike of the Alpine Fault from 8 km, beneath the highest topography, to 20 km in the adjacent areas.
Dynamical Response of Changjiang River Plume to a Severe Typhoon With the Surface Wave‐Induced Mixing
Authors: Zhang Zhiwei , Wu Hui , Yin Xunqiang , Qiao Fangli
Published: December 2018

Typhoons (or hurricanes) are the most energetic atmospheric forcing acting on coastal waters. Here in this study, we investigated the response of the summertime Changjiang River plume to a typical typhoon, Chan‐hom (1509), with a combination of field observation and numerical simulation. Surface wave‐induced mixing was considered in the model configuration. The results showed that the typical offshore‐extending summer Changjiang River plume completely disappeared under the influence of typhoon wind. Instead, it extended southward along the Zhejiang and Fujian (Zhe‐Min) coast as a typical wintertime Changjiang River plume. The along‐shelf plume extension lasted for extra ~10 days after the typhoon passage, until another strong weather event came. The competition between wind‐driven current and buoyancy‐driven current dominated the recovery of the Changjiang River plume. Through calculation, we found that the freshwater transported to the Zhe‐Min Coastal Water reached ~4.7 × 1010 m3 as influenced by typhoon Chan‐hom, which was ~5% of the total Changjiang River discharge in 2015 or ~12% of the total dry season Changjiang River discharge (October‐April) when the majority of Changjiang River plume extended to Zhe‐Min Coastal Water. The remote sensing data of chlorophyll‐α from Geostationary Ocean Color Imager also showed that significant algal bloom occurred when the southward extending Changjiang River plume retreated. Surface wave‐induced mixing caused by typhoon wind was found to be important in destroying the vertical plume stratification and elongating the recovery processes from the typhoon influence.
Increased α2-6 sialylation of endometrial cells contributes to the development of endometriosis
Authors: Choi Hee-Jin , Chung Tae-Wook , Choi Hee-Jung , Han Jung Ho , Choi Jung-Hye , Kim Cheorl-Ho , Ha Ki-Tae
Published: December 2018

Endometriosis is a disease characterized by implants of endometrial tissue outside the uterine cavity and is strongly associated with infertility. Focal adhesion of endometrial tissue to the peritoneum is an indication of incipient endometriosis. In this study, we examined the effect of various cytokines that are known to be involved in the pathology of endometriosis on endometrial cell adhesion. Among the investigated cytokines, transforming growth factor-β1 (TGF-β1) increased adhesion of endometrial cells to the mesothelium through induction of α2-6 sialylation. The expression levels of β-galactoside α2-6 sialyltransferase (ST6Gal) 1 and ST6Gal2 were increased through activation of TGF-βRI/SMAD2/3 signaling in endometrial cells. In addition, we discovered that terminal sialic acid glycan epitopes of endometrial cells engage with sialic acid-binding immunoglobulin-like lectin-9 expressed on mesothelial cell surfaces. Interestingly, in an in vivo mouse endometriosis model, inhibition of endogenous sialic acid binding by a NeuAcα2-6Galβ1-4GlcNAc injection diminished TGF-β1-induced formation of endometriosis lesions. Based on these results, we suggest that increased sialylation of endometrial cells by TGF-β1 promotes the attachment of endometrium to the peritoneum, encouraging endometriosis outbreaks.
Reduced TCA cycle rates at high hydrostatic pressure hinder hydrocarbon degradation and obligate oil degraders in natural, deep-sea microbial communities
Authors: Scoma Alberto , Heyer Robert , Rifai Ridwan , Dandyk Christian , Marshall Ian , Kerckhof Frederiek-Maarten , Marietou Angeliki , Boshker Henricus T S , Meysman Filip J R , Malmos Kirsten G , Vosegaard Thomas , Vermeir Pieter , Banat Ibrahim M , Benndorf Dirk , Boon Nico
Published: December 2018

Petroleum hydrocarbons reach the deep-sea following natural and anthropogenic factors. The process by which they enter deep-sea microbial food webs and impact the biogeochemical cycling of carbon and other elements is unclear. Hydrostatic pressure (HP) is a distinctive parameter of the deep sea, although rarely investigated. Whether HP alone affects the assembly and activity of oil-degrading communities remains to be resolved. Here we have demonstrated that hydrocarbon degradation in deep-sea microbial communities is lower at native HP (10 MPa, about 1000 m below sea surface level) than at ambient pressure. In long-term enrichments, increased HP selectively inhibited obligate hydrocarbon-degraders and downregulated the expression of beta-oxidation-related proteins (i.e., the main hydrocarbon-degradation pathway) resulting in low cell growth and CO2 production. Short-term experiments with HP-adapted synthetic communities confirmed this data, revealing a HP-dependent accumulation of citrate and dihydroxyacetone. Citrate accumulation suggests rates of aerobic oxidation of fatty acids in the TCA cycle were reduced. Dihydroxyacetone is connected to citrate through glycerol metabolism and glycolysis, both upregulated with increased HP. High degradation rates by obligate hydrocarbon-degraders may thus be unfavourable at increased HP, explaining their selective suppression. Through lab-scale cultivation, the present study is the first to highlight a link between impaired cell metabolism and microbial community assembly in hydrocarbon degradation at high HP. Overall, this data indicate that hydrocarbons fate differs substantially in surface waters as compared to deep-sea environments, with in situ low temperature and limited nutrients availability expected to further prolong hydrocarbons persistence at deep sea.
Vibrio coralliilyticus infection triggers a behavioural response and perturbs nutritional exchange and tissue integrity in a symbiotic coral
Authors: Gibbin E , Gavish A , Krueger T , Kramarsky-Winter E , Shapiro O , Guiet R , Jensen L , Vardi A , Meibom A
Published: December 2018

Under homoeostatic conditions, the relationship between the coral Pocillopora damicornis and Vibrio coralliilyticus is commensal. An increase in temperature, or in the abundance of V. coralliilyticus, can turn this association pathogenic, causing tissue lysis, expulsion of the corals’ symbiotic algae (genus Symbiodinium), and eventually coral death. Using a combination of microfluidics, fluorescence microscopy, stable isotopes, electron microscopy and NanoSIMS isotopic imaging, we provide insights into the onset and progression of V. coralliilyticus infection in the daytime and at night, at the tissue and (sub-)cellular level. The objective of our study was to connect the macro-scale behavioural response of the coral to the micro-scale nutritional interactions that occur between the host and its symbiont. In the daytime, polyps enhanced their mucus production, and actively spewed pathogens. Vibrio infection primarily resulted in the formation of tissue lesions in the coenosarc. NanoSIMS analysis revealed infection reduced 13C-assimilation in Symbiodinium, but increased 13C-assimilation in the host. In the night incubations, no mucus spewing was observed, and a mucus film was formed on the coral surface. Vibrio inoculation and infection at night showed reduced 13C-turnover in Symbiodinium, but did not impact host 13C-turnover. Our results show that both the nutritional interactions that occur between the two symbiotic partners and the behavioural response of the host organism play key roles in determining the progression and severity of host-pathogen interactions. More generally, our approach provides a new means of studying interactions (ranging from behavioural to metabolic scales) between partners involved in complex holobiont systems, under both homoeostatic and pathogenic conditions.
Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer
Authors: Jia Qingzhu , Wu Wei , Wang Yuqi , Alexander Peter B. , Sun Chengdu , Gong Zhihua , Cheng Jia-Nan , Sun Huaibo , Guan Yanfang , Xia Xuefeng , Yang Ling , Yi Xin , Wan Yisong Y. , Wang Haidong , He Ji , Futreal P. Andrew , Li Qi-Jing , Zhu Bo
Published: December 2018

Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy.
The propagation of active-passive interfaces in bacterial swarms
Authors: Patteson Alison E. , Gopinath Arvind , Arratia Paulo E.
Published: December 2018

Propagating interfaces are ubiquitous in nature, underlying instabilities and pattern formation in biology and material science. Physical principles governing interface growth are well understood in passive settings; however, our understanding of interfaces in active systems is still in its infancy. Here, we study the evolution of an active-passive interface using a model active matter system, bacterial swarms. We use ultra-violet light exposure to create compact domains of passive bacteria within Serratia marcescens swarms, thereby creating interfaces separating motile and immotile cells. Post-exposure, the boundary re-shapes and erodes due to self-emergent collective flows. We demonstrate that the active-passive boundary acts as a diffuse interface with mechanical properties set by the flow. Intriguingly, interfacial velocity couples to local swarm speed and interface curvature, raising the possibility that an active analogue to classic Gibbs-Thomson-Stefan conditions may control this boundary propagation.
Hartman effect for spin waves in exchange regime
Authors: Kłos Jarosław W. , Dadoenkova Yuliya S. , Rychły Justyna , Dadoenkova Nataliya N. , Lyubchanskii Igor L. , Barnaś Józef
Published: December 2018

Hartman effect for spin waves tunnelling through a barrier in a thin magnetic film is considered theoretically. The barrier is assumed to be created by a locally increased magnetic anisotropy field. The considerations are focused on a nanoscale system operating in the exchange-dominated regime. We derive the formula for group delay τgr of a spin wave packet and show that τgr saturates with increasing barrier width, which is a signature of the Hartman effect predicted earlier for photonic and electronic systems. In our calculations, we consider the general boundary conditions which take into account different strength of exchange coupling between the barrier and its surrounding. As a system suitable for experimental observation of the Hartman effect we propose a CoFeB layer with perpendicular magnetic anisotropy induced by a MgO overlayer.
HAI Peptide and Backbone Analogs—Validation and Enhancement of Biostability and Bioactivity of BBB Shuttles
Authors: Arranz-Gibert Pol , Prades Roger , Guixer Bernat , Guerrero Simón , Araya Eyleen , Ciudad Sonia , Kogan Marcelo J. , Giralt Ernest , Teixidó Meritxell
Published: December 2018

Low effectiveness and resistance to treatments are commonplace in disorders of the central nervous system (CNS). These issues concern mainly the blood-brain barrier (BBB), which preserves homeostasis in the brain and protects this organ from toxic molecules and biohazards by regulating transport through it. BBB shuttles—short peptides able to cross the BBB—are being developed to help therapeutics to cross this barrier. BBB shuttles can be discovered by massive exploration of chemical diversity (e.g. computational means, phage display) or rational design (e.g. derivatives from a known peptide/protein able to cross). Here we present the selection of a peptide shuttle (HAI) from several candidates and the subsequent in-depth in vitro and in vivo study of this molecule. In order to explore the chemical diversity of HAI and enhance its biostability, and thereby its bioactivity, we explored two new protease-resistant versions of HAI (i.e. the retro-D-version, and a version that was N-methylated at the most sensitive sites to enzymatic cleavage). Our results show that, while both versions of HAI are resistant to proteases, the retro-D-approach preserved better transport properties.
The effects of a human food additive, titanium dioxide nanoparticles E171, on Drosophila melanogaster - a 20 generation dietary exposure experiment
Authors: Jovanović Boris , Jovanović Nikola , Cvetković Vladimir J. , Matić Sanja , Stanić Snežana , Whitley Elizabeth M. , Mitrović Tatjana Lj.
Published: December 2018

In this study, fruit flies (Drosophila melanogaster) were exposed to an estimated daily human E171 consumption concentration for 20 generations. Exposure to E171 resulted in: a change in normal developmental and reproductive dynamics, reduced fecundity after repetitive breeding, increased genotoxicity, the appearance of aberrant phenotypes and morphologic changes to the adult fat body. Marks of adaptive evolution and directional selection were also exhibited. The larval stages were at a higher risk of sustaining damage from E171 as they had a slower elimination rate of TiO2 compared to the adults. This is particularly worrisome, since among the human population, children tend to consume higher daily concentrations of E171 than do adults. The genotoxic effect of E171 was statistically higher in each subsequent generation compared to the previous one. Aberrant phenotypes were likely caused by developmental defects induced by E171, and were not mutations, since the phenotypic features were not transferred to any progeny even after 5 generations of consecutive crossbreeding. Therefore, exposure to E171 during the early developmental period carries a higher risk of toxicity. The fact that the daily human consumption concentration of E171 interferes with and influences fruit fly physiological, ontogenetic, genotoxic, and adaptive processes certainly raises safety concerns.
An Automatic Classification Method on Chronic Venous Insufficiency Images
Authors: Shi Qiang , Chen Weiya , Pan Ye , Yin Shan , Fu Yan , Mei Jiacai , Xue Zhidong
Published: December 2018

Chronic venous insufficiency (CVI) affect a large population, and it cannot heal without doctors’ interventions. However, many patients do not get the medical advisory service in time. At the same time, the doctors also need an assistant tool to classify the patients according to the severity level of CVI. We propose an automatic classification method, named CVI-classifier to help doctors and patients. In this approach, first, low-level image features are mapped into middle-level semantic features by a concept classifier, and a multi-scale semantic model is constructed to form the image representation with rich semantics. Second, a scene classifier is trained using an optimized feature subset calculated by the high-order dependency based feature selection approach, and is used to estimate CVI’s severity. At last, classification accuracy, kappa coefficient, F1-score are used to evaluate classification performance. Experiments on the CVI images from 217 patients’ medical records demonstrated superior performance and efficiency for CVI-classifier, with classification accuracy up to 90.92%, kappa coefficient of 0.8735 and F1score of 0.9006. This method also outperformed doctors’ diagnosis (doctors rely solely on images to make judgments) with accuracy, kappa and F1-score improved by 9.11%, 0.1250 and 0.0955 respectively.
Fast oxygen dynamics as a potential biomarker for epilepsy
Authors: Farrell Jordan S. , Greba Quentin , Snutch Terrance P. , Howland John G. , Teskey G. Campbell
Published: December 2018

Changes in brain activity can entrain cerebrovascular dynamics, though this has not been extensively investigated in pathophysiology. We assessed whether pathological network activation (i.e. seizures) in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) could alter dynamic fluctuations in local oxygenation. Spontaneous absence seizures in an epileptic rat model robustly resulted in brief dips in cortical oxygenation and increased spectral oxygen power at frequencies greater than 0.08 Hz. Filtering oxygen data for these fast dynamics was sufficient to distinguish epileptic vs. non-epileptic rats. Furthermore, this approach distinguished brain regions with seizures from seizure-free brain regions in the epileptic rat strain. We suggest that fast oxygen dynamics may be a useful biomarker for seizure network identification and could be translated to commonly used clinical tools that measure cerebral hemodynamics.