bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal state and structure of lithospheric mantle beneath the Xing'an Massif, northeast China: Constraints from mantle xenoliths entrained by Cenozoic basalts
Authors: Guo Peng , Xu Wen‐Liang , Wang Chun‐Guang , Zhang Yan‐Long
Published: August 2018

The lithospheric mantle beneath the Xing'an Massif (XM), northeast China, was formed at the Paleoproterozoic or even earlier, but its thermal state and structure remain poorly understood. To address this issue, we calculate pressure–temperature (P–T) arrays for mantle xenoliths entrained by Cenozoic basalts from the XM, using major‐element‐based and rare earth element (REE)‐based two‐pyroxene thermometry as well as single clinopyroxene barometry. Samples (include spinel or garnet lherzolites and harzburgites, dunite and pyroxenite) come from the Keluo, Nuomin, and Aershan regions, which are located on either side of the North–South Gravity Lineament (NSGL). To the west of the NSGL, in the Nuomin and Aershan regions, mantle xenoliths yield consistent REE‐based and major‐element‐based temperatures, suggesting that these samples were derived from stable thermal conditions. Garnet peridotites from these regions yield pressures of 2.37–3.01 GPa and temperatures of 1066–1303°C, revealing a high geothermal gradient (corresponding to a surface heat flow of 70–80 mW/m2) and a crustal thicknesses of ~37 km. The lithosphere–asthenosphere boundary determined from the intersection of this geotherm with the mantle adiabat occurs at a depth of ~100 km, which is much shallower than the lithospheric thickness calculated by geophysical analyses (140–160 km). This discrepancy may have resulted from locally upwelling hot asthenosphere. Low‐temperature (800–900°C) peridotites from the Nuomin and Aershan are chemically fertile with low olivine Mg# values and high modal clinopyroxene contents. By contrast, high‐temperature (1050–1350°C) peridotites consist mainly of refractory harzburgites or clinopyroxene‐poor lherzolites. These facts reveal that the lithospheric mantle beneath the Nuomin and Aershan regions is characterized by juvenile mantle dominating shallow levels and ancient mantle occurring at greater depths. To the east of the NSGL, some Keluo mantle xenoliths yield higher REE‐based temperatures (839–863°C) than major‐element‐based temperatures (<800°C), indicating cooling by thermal relaxation. This cooling process produced a low geothermal gradient (~45 mW/m2) in the lithosphere beneath the Keluo region. The mantle xenoliths comprise both fertile lherzolites and refractory harzburgites without correlation between mineral compositions and temperatures, suggesting that the lithospheric mantle beneath the Keluo region is characterized by juvenile mantle mixed with ancient mantle at all depths. The results show contrasting thermal state and structure of the lithospheric mantle on either side of the NSGL within the XM, which are attributed to a previous cooling process in the Keluo region and local upwelling of hot asthenosphere beneath the Aershan and Nuomin regions.
Role of physical activity in ameliorating neuropsychiatric symptoms in Alzheimer disease: A narrative review
Authors: Veronese Nicola , Solmi Marco , Basso Cristina , Smith Lee , Soysal Pinar
Published: August 2018

Objective

Neuropsychiatric symptoms (NPs) affect almost all patients with Alzheimer disease (AD). Because of the complications associated with the pharmacological treatment, nonpharmacological treatment (such as physical activity) can be considered as an additional complementary treatment option for NPs. The aim of this review is to evaluate the impact of physical activity on NPs in patients with AD.

Methods

We searched Pubmed and Google Scholar for potential eligible articles until March 1, 2018.

Results

Although there are contradictory results showing the impact of physical exercise on NPs, most of them reported that it had a significant effect on depression and sleep disturbances in patients with AD. The beneficial effects could be explained through several mechanisms, including modulated production of neurotransmitters; increasing neurotrophins, such as brain‐derived neurotrophic factor; reduction of oxidative stress and inflammation; elevation of cerebral blood flow; hypothalamic pituitary adrenal axis regulation; and support of neurogenesis and synaptogenesis. Physical activity can also improve cardiovascular risk factors, which may exaggerate NPs. There is limited evidence for other NPs such as agitation, disinhibition, apathy, hallucinations, and anxiety.

Conclusion

Physical activity may ameliorate depression and sleep disturbances in patients with AD. Therefore, physical activity can be a “potential” add‐on treatment to drugs to reduce or prevent these symptoms onset and recurrence in patients with AD. However, further studies are needed to focus on relationship between physical activity and other NPs.
Going beyond incentivizing formal health providers: Evidence from the Rwanda Community Performance‐Based Financing program
Authors: Shapira Gil , Kalisa Ina , Condo Jeanine , Humuza James , Mugeni Cathy , Nkunda Denis , Walldorf Jeanette
Published: August 2018

Pay‐for‐performance programs are introduced in an increasing number of low‐ and middle‐income countries with the goal of reducing maternal and child mortality and morbidity through increased health service utilization and quality. Although most programs incentivize formal health providers, some constraints to utilization might be better alleviated by incentivizing other actors in the health care system. This paper presents results from a randomized controlled trial set to evaluate the effects of two incentive schemes that were introduced on top of Rwanda's national Performance‐Based Financing program at the health facility level. One scheme rewarded community health worker cooperatives for the utilization of five services by their communities. The second scheme provided in‐kind transfers to users of three services. The analysis finds no impact of the cooperative performance payments on coverage of the targeted services, behaviors of community health workers, or outcomes at the cooperative level. Although health centers experienced frequent stock outs of the gifts, the demand‐side intervention significantly increased timely antenatal care by 9.3 percentage points and timely postnatal care by 8.6 percentage points. This study shows that demand‐side incentives can increase service utilization also when provided in addition to a supply‐side pay‐for‐performance scheme.
MERIT: Systematic Analysis and Characterization of Mutational Effect on RNA Interactome Topology
Authors: Li Yongsheng , McGrail Daniel J. , Xu Juan , Li Junyi , Liu Ning‐Ning , Sun Ming , Lin Richard , Pancsa Rita , Zhang Jiwei , Lee Ju‐Seog , Wang Hui , Mills Gordon B. , Li Xia , Yi Song , Sahni Nidhi
Published: August 2018

The interaction between RNA‐binding proteins (RBPs) and RNA plays an important role in regulating cellular function. However, decoding genome‐wide protein–RNA regulatory networks as well as how cancer‐related mutations impair RNA regulatory activities in hepatocellular carcinoma (HCC) remains mostly undetermined. We explored the genetic alteration patterns of RBPs and found that deleterious mutations are likely to occur on the surface of RBPs. We then constructed protein–RNA interactome networks by integration of target binding screens and expression profiles. Network analysis highlights regulatory principles among interacting RBPs. In addition, somatic mutations selectively target functionally important genes (cancer genes, core fitness genes, or conserved genes) and perturb the RBP–gene regulatory networks in cancer. These regulatory patterns were further validated using independent data. A computational method (Mutational Effect on RNA Interactome Topology) and a web‐based, user‐friendly resource were further proposed to analyze the RBP–gene regulatory networks across cancer types. Pan‐cancer analysis also suggests that cancer cells selectively target “vulnerability” genes to perturb protein–RNA interactome that is involved in cancer hallmark–related functions. Specifically, we experimentally validated four pairs of RBP–gene interactions perturbed by mutations in HCC, which play critical roles in cell proliferation. Based on the expression of perturbed RBP and target genes, we identified three subtypes of HCC with different survival rates. Conclusion: Our results provide a valuable resource for characterizing somatic mutation‐perturbed protein–RNA regulatory networks in HCC, yielding valuable insights into the genotype–phenotype relationships underlying human cancer, and potential biomarkers for precision medicine.
Remembering rewarding futures: A simulation‐selection model of the hippocampus
Authors: Jung Min Whan , Lee Hyunjung , Jeong Yeongseok , Lee Jong Won , Lee Inah
Published: August 2018

Despite tremendous progress, the neural circuit dynamics underlying hippocampal mnemonic processing remain poorly understood. We propose a new model for hippocampal function—the simulation‐selection model—based on recent experimental findings and neuroecological considerations. Under this model, the mammalian hippocampus evolved to simulate and evaluate arbitrary navigation sequences. Specifically, we suggest that CA3 simulates unexperienced navigation sequences in addition to remembering experienced ones, and CA1 selects from among these CA3‐generated sequences, reinforcing those that are likely to maximize reward during offline idling states. High‐value sequences reinforced in CA1 may allow flexible navigation toward a potential rewarding location during subsequent navigation. We argue that the simulation‐selection functions of the hippocampus have evolved in mammals mostly because of the unique navigational needs of land mammals. Our model may account for why the mammalian hippocampus has evolved not only to remember, but also to imagine episodes, and how this might be implemented in its neural circuits.
Stakeholders analysis of merging social health insurance funds in Iran: what kind of interests they may gain or lose?
Authors: Bazyar Mohammad , Rashidian Arash , Sakha Minoo Alipouri , Doshmangir Leila , Rahimi Nouroddin , Ranjbar Mohammad , Sagha Abolfazl Seyyedeh Fatemeh , Tabatabaei Lotfi Seyed Moussa , Olyaeemanesh Alireza
Published: August 2018

Iran passed a Law in 2010 to merge all existing health insurance funds physically together. This stakeholder analysis aimed at revealing that what benefits the stakeholders might lose or gain as a result of merging health insurance schemes in Iran, which make them to oppose or support it. This was a qualitative study conducted in 2014. Sixty semi‐structured face‐to‐face interviews were conducted. Purposive and snowball samplings with maximum heterogeneity samples were used for selecting interviewees. Government is not willing to undertake more financial commitment. Existing health insurance schemes like Social Security Organization and minor well‐resourced health insurance funds and also worker unions are unwilling to lose their financial and organizational autonomy, to share their benefits with other less privileged groups, or face likely financial challenges in running their health facilities like hospitals. Top managers and workforces are worried to lose their job, salary, or organizational positions. Ministry of Cooperation, Labour, and Social Welfare does not want to lose its control on health insurance schemes. Ministry of Health and Medical Education and Iran Health Insurance Organization are among actors that support the insurance funds merging policy. Successful implementing of consolidation requires taking into account the interests of different stakeholders.
Opinions and evaluations of stakeholders in the implementation of the public‐private partnership (PPP) model in integrated health campuses (city hospitals) in Turkey
Authors: Top Mehmet , Sungur Cuma
Published: August 2018

Purpose

This study aimed to define the public‐private partnership (PPP) model, eliciting the views and assessments of stakeholders and identifying associated health policies and planning issues.

Method

It uses qualitative research methods to examine the extent to which PPPs promote or interfere with the provision of health services, equality, efficiency, quality, health tourism, and initiatives to strengthen the national economy. Having selected an appropriate sample, researchers approached bureaucrats and experts from the Ministry of Health, Social Security Institution, Ministry of Development, Ministry of Finance, NGOs, and other state institutions and organizations. A total of 83 people were asked to complete a semi‐structured questionnaire. The qualitative research data were analyzed using a descriptive‐analysis method; a content analysis was carried out using a computer‐based qualitative research program, MAXQDA Versions 11.

Results

The majority of participants expressed positive opinions about PPPs, their applicability in Turkey, and the financial viability and scope of PPPs in the health sector. They also commented on the aims, advantages, and disadvantages of such partnerships. The majority of participants believed that a PPP was an appropriate finance model for the integrated health‐campus substructure of Turkey's health sector. The most positive views were expressed by public and private sector‐stakeholders, while some negative views were voiced by NGO representatives.

Conclusion

This study identified and assessed integrated health‐campus projects to determine the aim, suitability, advantages, and disadvantages of the model in the health sector, particularly in relation to the cost, quality, and availability of health services. This study discusses the current positive and negative effects of integrated health‐campus implementation.
Study on the dominant causes of streamflow alteration and effects of the current water diversion in the Tarim River Basin, China
Authors: Yang Fan , Xue Lianqing , Wei Guanghui , Chi Yixia , Yang Guang
Published: August 2018

Understanding the dominant causes of streamflow alteration and effects of the current water diversion scheme is beneficial for sustainable management of water resources in an arid area. This study presents a quantitative attribution of the run‐off changes between headstreams and mainstream from 1960 to 2015 using the Choudhury–Yang equation and evaluates the effects of 18 times of ecological water conveyance in the lower reaches of the Tarim River Basin (TRB). Our results suggest that climate change was the primary determinant of increase of the streamflow in the headstreams from 2000 to 2015. While in the mainstream, human activities played a dominant role in deduction in the streamflow with the contribution of 54.8–355.6%. Eighteen episodes of ecological water conveyance have a positive effect on rising groundwater level and are highly related to seed falling time of Shrub and Perennial herbaceous and Annual herbaceous except for Arbor. It indicates that restoring the long‐term drying of the lower reaches through continuous water conveyance is feasible, although the existing programme has not restored the entire riparian system. Our study suggests that it is necessary to adopt an integrated approach for water resources allocation rather than relying on a single tributary contribution in the TRB.
ANO7 is associated with aggressive prostate cancer
Authors: Kaikkonen Elina , Rantapero Tommi , Zhang Qin , Taimen Pekka , Laitinen Virpi , Kallajoki Markku , Jambulingam Dhanaprakash , Ettala Otto , Knaapila Juha , Boström Peter J. , Wahlström Gudrun , Sipeky Csilla , Pursiheimo Juha‐Pekka , Tammela Teuvo , Kellokumpu‐Lehtinen Pirkko‐Liisa ,   PRACTICAL Consortium, Fey Vidal , Maehle Lovise , Wiklund Fredrik , Wei Gong‐Hong , Schleutker Johanna
Published: August 2018

Prostate cancer is one of the most common and heritable human cancers. Our aim was to find germline biomarkers that can predict disease outcome. We previously detected predisposing signals at 2q37, the location of the prostate specific ANO7 gene. To investigate, in detail, the associations between the ANO7 gene and PrCa risk and disease aggressiveness, ANO7 was sequenced in castration resistant tumors together with samples from unselected PrCa patients and unaffected males. Two pathogenic variants were discovered and genotyped in 1769 patients and 1711 unaffected males. Expression of ANO7 vs. PrCa aggressiveness was investigated. Different databases along with Swedish and Norwegian cohorts were used for validation. Case–control and aggressive vs. nonaggressive association analyses were performed against risk and/or cancer aggressiveness. The ANO7 mRNA level and patient survival were analyzed using expression data from databases. Variant rs77559646 showed both risk (OR 1.40; p = 0.009, 95% CI 1.09–1.78) and association with aggressive PrCa (Genotype test p = 0.04). It was found to be an eQTL for ANO7 (Linear model p‐values for Finnish patients p = 0.009; Camcap prostate tumor p = 2.53E‐06; Stockholm prostate tumor cohort p = 1.53E‐13). rs148609049 was not associated with risk, but was related to shorter survival (HR 1.56; 95% CI 1.03–2.36). High ANO7 expression was independently linked to poor survival (HR 18.4; 95% CI 1.43–237). ANO7 genotypes correlate with expression and biochemical relapse, suggesting that ANO7 is a potential PrCa susceptibility gene and that its elevated expression correlates with disease severity and outcome.
Overexpression of CDCA7 predicts poor prognosis and induces EZH2‐mediated progression of triple‐negative breast cancer
Authors: Ye Liping , Li Fengyan , Song Yipeng , Yu Donglin , Xiong Zhenchong , Li Yue , Shi Tianyi , Yuan Zhongyu , Lin Chuyong , Wu Xianqiu , Ren Liangliang , Li Xinghua , Song Libing
Published: August 2018

Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with high proliferative and metastatic phenotypes. CDCA7, a new member of the cell division cycle associated family of genes, is involved in embryonic development and dysregulated in various types of human cancer. However, the biological role and molecular mechanism of CDCA7 in TNBC have not been defined. Herein, we found that CDCA7 was preferentially and markedly expressed in TNBC cell lines and tissues. High expression of CDCA7 was associated with metastatic relapse status and predicted poorer disease‐free survival in patients with TNBC. We observed that CDCA7 silencing in TNBC cell lines effectively impaired cell proliferation, invasion and migration in vitro. Importantly, depletion of CDCA7 strongly reduced the tumorigenicity and distant colonization capacities of TNBC cells in vivo. Furthermore, CDCA7 increased the expression of EZH2, a marker of aggressive breast cancer that is involved in tumor progression, by enhancing the transcriptional activity of its promoter. This increase in EZH2 expression was essential for the CDCA7‐mediated effects on TNBC progression. Finally, our immunohistochemical analysis revealed that the CDCA7/EZH2 axis was clinical relevant. These findings suggest CDCA7 plays a crucial role in TNBC progression by transcriptionally upregulating EZH2 and might be a potential prognostic factor and therapeutic target in TNBC.
Understanding the Role of Escherichia coli Hydrogenases and Formate Dehydrogenases in the FOF1‐ATPase Activity during the Mixed Acid Fermentation of Mixture of Carbon Sources
Authors: Gevorgyan Heghine , Trchounian Armen , Trchounian Karen
Published: August 2018

During fermentation Escherichia coli produces di‐hydrogen (H2) via reversible membrane‐bound [Ni‐Fe]‐hydrogenases (Hyd). This study describes the total and N,N′‐dicyclohexylcarbodiimide (DCCD) inhibited ATPase activity and H2 production at various pHs in E. coli wild type and mutants encoding Hyd enzymes and formate dehydrogenases (FDH) on fermentation of glucose, glycerol, and formate. The highest total ATPase activity was detected at pH 7.5 in hyaB hybC selC (lacking large subunits of Hyd‐1 and Hyd‐2 and FDH, respectively) triple mutant. This ATPase activity was mainly due to the proton‐translocating ATPase but in FDH mutant the DCCD inhibition was less compared to wild type. Potassium ions stimulated total ATPase activity at pH 5.5 ~50% and ~35% in wild type and hypF (lacking all Hyd enzymes) mutant, respectively. Moreover, K+ also stimulated DCCD inhibited ATPase activity ~1.7‐fold–2‐fold in strains where FDH was absent only at pH 5.5. DCCD inhibited H2 production only at pH 5.5 in all assays. Taken together it is suggested that at low pH, FDH, and Hyd enzymes are linked with the FOF1‐ATPase for regulating and maintaining the cytoplasmatic pH and thus proton motive force generation. FDH and Hyd enzymes have impact on the FOF1‐ATPase activity depending on external pH and potassium ions. © 2018 IUBMB Life, 70(10):1040–1047, 2018
miR‐381‐3p restrains cervical cancer progression by downregulating FGF7
Authors: Shang Anquan , Zhou Cheng , Bian Ganxia , Chen Wei , Lu Wenying , Wang Weiwei , Li Dong
Published: August 2018

This study aimed at elucidating the molecular mechanism of miR‐381‐3p in cervical cancer progression, which may provide a novel therapeutic target for patients with cervical cancer. The expression of miR‐381‐3p was confirmed by quantitative reverse transcription polymerase chain reaction. Microarray analysis was conducted to screen out differentially expressed genes, and the target gene of microRNA (miRNA) was predicted on TargetScan. Dual‐luciferase reporter assay then verified the targeting relationship between miR‐381‐3p and FGF7. The protein expression of FGF7 was examined via Western blot assay. Colony formation assay was used to detect the cell proliferation, while flow cytometry was used to analyze cell cycle and apoptosis. The influence of miR‐381‐3p and FGF7 on cell migration and invasion was confirmed by transwell migration/invasion assay. Finally, we demonstrated that miR‐381‐3p was lowly expressed, while FGF7 was highly expressed in cervical cancer cells. There was a direct target relationship and a negative correlation between miR‐381‐3p and FGF7. miR‐381‐3p could downregulate FGF7 expression, inhibiting cell proliferation and metastasis, and inducing cell cycle arrest and apoptosis in cervical cancer.
Computational optimization of in vitro parameters for di‐(2‐ethylhexyl) phthalate production from Anabaena circinalis
Authors: Sarkar Aratrika , Bagavananthem Andavan Gowri shankar
Published: August 2018

Di‐(2‐ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant, and finds extensive commercial application as a plasticizer to reduce the rigidity of polyvinyl chloride. Besides numerous negative impacts on environment and public health, the compound exhibits acute bioactivity against microbes and has therapeutic value too. Considering this biochemical significance, searching of its new biogenic sources has become an active area of research. Here, DEHP is identified from the biomass of a toxic strain of Anabaena circinalis, which is quite unobvious, and simultaneously, the in vitro physical conditions are optimized by using a swarm‐based multiparameter optimization technique. A purified fraction collected from column chromatography is subjected to gas chromatography (GC) to fetch the compound peak and then subsequent mass analysis for its identification. The mass spectrum describes the molecular weight along with the structure of DEHP with 99.9% experimental accuracy. An experimental observation table has been used to frame a fitness function using the curve fitting approach when temperature (T), light and dark period (LD), and duration of subculture cycle (DSC) are considered as the target parameters to be optimized. The optimum values obtained for T, LD, and DSC are 20°C, 14:10 hour light and dark ratio approximately, and 40 days, respectively. This experimental finding of A. circinalis FSS 124 as a novel source of DEHP and subsequent optimization using soft computing tools might be a benchmark for process optimization in biological research.
ETS1 induces transforming growth factor β signaling and promotes epithelial‐to‐mesenchymal transition in prostate cancer cells
Authors: Rodgers Jamie J. , McClure Robert , Epis Michael R. , Cohen Ronald J. , Leedman Peter J. , Harvey Jennet M. ,   Australian Prostate Cancer BioResource, Thomas Marc A. , Bentel Jacqueline M.
Published: August 2018

Expression of the transcriptional regulator, E26 transformation‐specific 1 (ETS1), is elevated in human prostate cancers, and this is associated with more aggressive tumor behavior and a rapid progression to castrate‐resistant disease. Multiple ETS1 isoforms with distinct biological activities have been characterized and in 44 matched nonmalignant and malignant human prostate specimens, messenger RNAs for two ETS1 isoforms, ETS1p51 and ETS1p42, were detected, with ETS1p51 levels significantly lower in prostate tumor compared to matched nonmalignant prostate tissues. In contrast, ETS1p51 protein, the only ETS1 isoform detected, was expressed at significantly higher levels in malignant prostate. Analysis of epithelial‐to‐mesenchymal transition (EMT)–associated genes regulated following overexpression of ETS1p51 in the LNCaP prostate cancer cell line predicted promotion of transforming growth factor β (TGFβ) signaling and of EMT. ETS1p51 overexpression upregulated cellular levels of the EMT transcriptional regulators, ZEB1 and SNAIL1, resulted in reduced expression of the mesenchymal marker vimentin with concomitantly elevated levels of claudin 1, an epithelial tight junction protein, and increased prostate cancer cell migration and invasion. ETS1p51‐induced activation of the pro‐EMT TGFβ signaling pathway that was predicted in polymerase chain reaction arrays was verified by demonstration of elevated SMAD2 phosphorylation following ETS1p51 overexpression. Attenuation of ETS1p51 effects on prostate cancer cell migration and invasion by inhibition of TGFβ pathway signaling indicated that ETS1p51 effects were in part mediated by induction of TGFβ signaling. Thus, overexpression of ETS1p51, the predominant ETS1 isoform expressed in prostate tumors, promotes an EMT program in prostate cancer cells in part via activation of TGFβ signaling, potentially accounting for the poor prognosis of ETS1‐overexpressing prostate tumors.
Ferroptosis‐inducing agents enhance TRAIL‐induced apoptosis through upregulation of death receptor 5
Authors: Lee Young‐Sun , Lee Dae‐Hee , Jeong So Yeon , Park Seong Hye , Oh Sang Cheul , Park Yong Seok , Yu Jian , Choudry Haroon A , Bartlett David L , Lee Yong J
Published: August 2018

Ferroptosis is considered genetically and biochemically distinct from other forms of cell death. In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death. When human colon cancer HCT116, CX‐1, and LS174T cells were treated with ferroptotic agents such as sorafenib (SRF), erastin, and artesunate, data from immunoblot assay showed that ferroptotic agents induced endoplasmic reticulum (ER) stress and the ER stress response‐mediated expression of death receptor 5 (DR5), but not death receptor 4. An increase in the level of DR5, which is activated by binding to tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and initiates apoptosis, was probably responsible for synergistic apoptosis when cells were treated with ferroptotic agent in combination with TRAIL. This collateral effect was suppressed in C/EBP (CCAAT‐enhancer‐binding protein)‐homologous protein (CHOP)‐deficient mouse embryonic fibroblasts or DR5 knockdown HCT116 cells, but not in p53‐deficient HCT116 cells. The results from in vitro studies suggest the involvement of the p53‐independent CHOP/DR5 axis in the synergistic apoptosis during the combinatorial treatment of ferroptotic agent and TRAIL. The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor‐bearing mice.
Dynamic perspectives into the mechanisms of mutation‐induced p53‐DNA binding loss and inactivation using active perturbation theory: Structural and molecular insights toward the design of potent reactivators in cancer therapy
Authors: Olotu Fisayo. A. , Soliman Mahmoud E. S.
Published: August 2018

The DNA‐binding ability of p53 represents the crux of its tumor suppressive activities, which involves transcriptional activation of target genes responsible for apoptosis and cell‐cycle arrest. Mutational occurrences within or in close proximity to the DNA‐binding surface of p53 have accounted for the loss of direct DNA‐binding ability and inactivation implicated in many cases of cancer. Moreover, the design of therapeutic compounds that can restore DNA‐binding ability in p53 mutants has been identified as a way forward in curtailing their oncogenic activities. However, there is still the need for more insights into evaluate the perturbations that occur at the DNA‐binding interface of mp53 relative to DNA‐binding loss, inactivation, and design of potent reactivators, hence the purpose of this study. Therefore, we evaluated p53‐structural (R175H) and contact (R273C) mutational effects using tunnel perturbation analysis and other computational tools. We identified significant perturbations in the active tunnels of p53, which resulted in altered geometry and loss, unlike in the wild‐type p53. This corroborated with structural, DNA‐binding, and interaction network analysis, which showed that loss of flexibility, repulsion of DNA‐interactive residues, and instability occurred at the binding interface of both mutants. Also, these mutations altered bonding interactions and network topology at the DNA‐binding interface, resulting in the reduction of p53‐DNA binding proximity and affinity. Therefore, these findings would aid the structure‐based design of novel chemical entities capable of restoring p53‐DNA binding and activation.
Osteocyte‐intrinsic mTORC1 signaling restrains trabecular bone accrual in mice
Authors: Liu Qingbai , Liu Cunchang , Yang Yanjun , Yang Huilin , Chen Jianquan
Published: August 2018

Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling plays important physiological roles in bone homeostasis by regulating multiple steps of osteoblast differentiation as well as its activity. However, its potential role in osteocytes has not been explored. In this study, we deleted Raptor, a specific and essential component of mTORC1, in osteocytes using Dmp1‐Cre. Deletion of Raptor in osteocytes did not affect bone development and growth, but caused compartment‐specific effects on bone mass. Osteocyte‐specific deletion of Raptor had no obvious effect on cortical bone compartments, but led to increased trabecular bone mass. Mechanistically, Raptor deletion resulted in decreased bone resorption without altering bone formation activity. Thus, our study revealed an unexpected role of osteocyte‐intrinsic mTORC1 signaling in limiting trabecular bone mass, suggesting that osteocyte‐specific inhibition of mTORC1 may be used as a novel approach to treatment of osteoporosis.
Effect of the autism‐associated lncRNA Shank2‐AS on architecture and growth of neurons
Authors: Luo Ting , Liu Ping , Wang Xiao‐Yan , Li Le‐Zhi , Zhao Li‐Ping , Huang Jin , Li Ya‐Min , Ou Jin‐Lan , Peng Xiao‐Qing
Published: August 2018

The pathogenic mechanism of autism is complex, and current research has shown that long noncoding RNAs (lncRNAs) may play important roles in this process. The antisense lncRNA of SH3 and multiple ankyrin repeat domains 2 (Shank2‐AS) is upregulated in patients with autism spectrum disorder (ASD), whereas the expression of its sense strand gene Shank2 is downregulated. In neuronal cells, Shank2‐AS and Shank2 can form a double‐stranded RNA and inhibit Shank2 expression. Overexpression of Shank2‐AS decreases neurite numbers and lengths, thereby inhibiting the proliferation of neuronal cells and promoting their apoptosis. Overexpression of Shank2 inhibits the abovementioned effects of Shank2‐AS, and transfection of a vector containing the 10th intron of Shank2 (Shank2‐AS is reverse‐transcribed from this region) also blocks the function of Shank2‐AS. Shank2 small interfering RNA plays a role similar to Shank2‐AS. Therefore, Shank2‐AS is abnormally expressed in patients with ASD and may affect the structure and growth of neurons by regulating Shank2 expression, thereby facilitating the development of ASD.
High expression of miR‐510 was associated with CGG expansion located at upstream of FMR1 into full mutation
Authors: Fazeli Zahra , Ghaderian Sayyed Mohammad Hossein , Najmabadi Hossein , Omrani Mir Davood
Published: August 2018

MicroRNAs (miRNAs) have been found to play an important role in the regulation of gene expression in eukaryotic organisms at the posttranscriptional level. More than half of miRNA genes have been recognized to be located in different fragile sites. Among them, miR‐510 was located on chromosome X in the 27.3Xq region, flanking to a fragile X site. The CGG expansion and its methylation at the promoter of FMR1 located in this fragile site were associated with clinical symptoms of fragile X syndrome (FXS). The aim of the current study was to investigate whether the miR‐510 expression was correlated with the CGG expansion of FMR1 in female carriers of full mutation. For this purpose, mesenchymal stem cells were isolated from peripheral blood of FMR1 full mutation female carriers. After differentiation of these cells into neuronal cells, the expression of miR‐510 was analyzed by quantitative polymerase chain reaction. Furthermore, the target genes of miR‐510 in the nervous system were also predicted by in silico method. The obtained results indicated that the CGG expansion of FMR1 was associated with the enhanced expression of miR‐510. Furthermore, the bioinformatics analysis suggested that VHL and PPP2R5E genes could be considered as the most important target genes of miR‐510 in the nervous system. This study showed that miR‐510 and its target genes, specifically VHL and PPP2R5E, may represent the new targets for future therapy options of FXS.
Dynamics of steroid‐induced oocyte maturation in three amphibian species: Mathematical modeling and simulation
Authors: Manzano Carolina , Benzal Maria Graciela , Zelarayán Liliana Isabel
Published: August 2018

Oocyte maturation in vertebrates involves morphological, biochemical, and functional changes through which meiosis, previously arrested in Profase I, is resumed. Within these changes, germinal vesicle breakdown (GVBD) constitutes morphological evidence of the resumption of the cellular cycle. Sex steroids (progestins and androgens) play a key role in oocyte maturation and are considered inducers of this process. The aims of this study were to analyze the effect of sex steroids on the oocyte maturation of amphibians and to model and simulate the dynamics of this process through the experimental data obtained. The oocytes of sexually mature females of Scinax fuscovarius, Pleurodema borellii, and Physalaemus biligonigerus were treated with different concentrations (0.001–1 µM) of sex steroids progesterone (P
4) and testosterone (T) for 24 hr. Dose– and time–response curves were performed with the results achieved. Sex steroids induced oocyte maturation in a dose‐dependent manner in all three species. The dose at which the highest maturation percentage was found was 1 μM. No significant differences were observed between GVBD percentages of P
4 and T. However, time–response curves show that oocytes responded earlier and achieved higher GVBD percentages when treated with P
4. Gompertz mathematical model was proposed in this study to simulate GVBD dynamics. This model properly fits the corresponding experimental data and allows the analysis of the behavior of oocyte maturation in amphibians and the quantification of parameters with biological meaning that are indicative of sex steroids efficiency in this process.
Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: Evidence from 8662 subjects and a structural analysis
Authors: Noureddini Mahdi , Mobasseri Narges , Karimian Mohammad , Behjati Mohaddeseh , Nikzad Hossein
Published: August 2018

Background

The Arg399Gln polymorphism in the X‐ray repair cross‐complementing group 1 gene (XRCC1) may alter the risk of prostate cancer (PCa). The present study aimed to investigate the association of the XRCC1‐Arg399Gln polymorphism with PCa risk in an Iranian population, as followed by a meta‐analysis and an in silico analysis.

Methods

In a case–control study, 360 subjects were included (180 men with PCa and 180 healthy controls). XRCC1‐Arg399Gln genotyping was performed using the polymerase chain reaction‐restriction fragment length polymorphism method. In the meta‐analysis, 14 eligible studies were included to which our case–control data were added to estimate the pooled odds ratios. Some bioinformatics tools were employed to evaluate the effects of Arg399Gln substitution on molecular aspects of the XRCC1 protein.

Results

Our case–control study revealed a significant association between the XRCC1‐Arg399Gln polymorphism and PCa risk. The data from overall meta‐analysis showed significant associations between the mentioned polymorphism and PCa risk in allelic and recessive genetic models. In addition, we observed statistically significant associations in stratified analyses by ethnicity, sample size and source of controls. Our in silico analysis showed that Arg399Gln substitution could be damaging with respect to the function and structure of the XRCC1 protein.

Conclusions

Based on these results, the XRCC1‐Arg399Gln polymorphism might be a risk factor for PCa and it could be considered as a prognostic and predictive biomarker for susceptible men.
A regional frequency analysis of UK sub‐daily extreme precipitation and assessment of their seasonality
Authors: Darwish Motasem M. , Fowler Hayley J. , Blenkinsop Stephen , Tye Mari R.
Published: August 2018

Floods related to extreme precipitation events, especially intense, short‐duration precipitation, may cause significant damage in urbanized areas, including transport infrastructure, electricity networks, and property. These events are expected to increase in frequency with climate change but their characteristics, at either hourly or multi‐hourly timescales, have been little studied due to short and poor quality data records. We examine annual maximum (AMAX) hourly and multi‐hourly (3, 6, 12, and 24 hr) precipitation accumulations in the United Kingdom using a quality‐controlled hourly precipitation data set for the period 1992–2014. We describe their seasonality and diurnal cycle and use a regional frequency analysis (RFA) approach with L‐moments to produce at‐site return level estimates, and then use existing extreme precipitation regions to provide regional‐scale return levels. The analysis shows a clear seasonality and the dominant occurrence of short‐duration AMAX in summer with similar seasonality for 1 and 3 hr accumulation periods in some regions, while longer‐duration AMAX (12 and 24 hr) behave similarly to each other in all regions but are distributed over a longer period including late autumn and winter. The diurnal cycle of 1 hr AMAX indicates that most extremes occur during the afternoon, with a peak typically between 1400 and 1700, especially in southern and eastern regions. However, we also demonstrate that existing regions for UK daily extremes are not able to adequately reflect differences at shorter durations and that new regions should be created. These results provide new insights to help in designing urban drainage systems and infrastructure, including the need for new scaling relationships between sub‐daily and design accumulation periods.
A simple gradient equilibrium method for better separation in countercurrent chromatography
Authors: Quan Kai‐Jun , Xi Xing‐jun , Huang Xin‐Yi , Duan Wen‐Da , Pei Dong , Di Duo‐Long
Published: August 2018

The stationary phase retention is one of the most important parameters in countercurrent chromatography. In this work, a simple gradient equilibrium method was developed to further improve the stationary phase retention based on the optimized condition in the traditional equilibrium model. Meanwhile, this novel gradient equilibrium method was used to separate three flavone model compounds and compared with the conventional isocratic equilibrium method to evaluate the separation efficiency. The results show that better resolution or shorter separation time could be achieved with gradient equilibrium compared to isocratic equilibrium. So this novel equilibrium method has enormous potential for obtaining a better separation or saving the separating time in the preparative separation of target compounds.
Profiling of headspace volatiles from Escherichia coli cultures using silicone‐based sorptive media and thermal desorption GC–MS
Authors: Devaraj Harish , Pook Chris , Swift Simon , Aw Kean C. , McDaid Andrew J.
Published: August 2018

Headspace sorptive extraction technique using silicone based sorptive media coated stir bars is used for the first time here to extract, identify, and quantify heavy volatile organic compounds present in Escherichia coli culture headspace. Detection of infection presence is largely accomplished in laboratories through physical sampling and subsequent growth of cultures for biochemical testing. The use of volatile biomarkers released from pathogens as indicators for pathogenic presence can vastly reduce the time needed whilst improving the success rates for infection detection. To validate this, by using a contactless headspace sorptive extraction technique, the volatile compounds released from E. coli, grown in vitro, have been extracted and identified. Two different sorptive media for extracting these headspace volatiles were compared in this study and the identified volatiles were quantified. The large phase volume and wider retention of this sorptive technique compared to traditional sampling approach enabled preconcentration and collection of wider range of volatiles towards developing an extensive database of such heavy volatiles associated with E. coli. This supplements the existing data of potential bacterial markers and use of internal standards in these tests allows semi‐quantitative estimation of these compounds towards the development and optimization of novel pathogen sensing devices.
Selective separation and purification of β‐estradiol from marine sediment using an optimized core–shell molecularly imprinted polymer
Authors: He Xiuping , Lian Ziru , Wang Jiangtao
Published: August 2018

The core–shell molecularly imprinted polymers were optimized to provide reliable connections that allow molecularly imprinted polymers to be fixed on SiO2 surface for the efficient separation and purification of β‐estradiol from marine sediment for the first time. To achieve the goal, different preparation methods were used and finally the polymer using 3‐methacryloxypropyltrimethoxysilane as coupling agent exhibited the best result, which further confirmed that 3‐methacryloxypropyltrimethoxysilane played an indispensable role on improving the inter‐particle connections. An offline molecularly imprinted solid‐phase extraction with high‐performance liquid chromatography method was successfully applied to the isolation and enrichment of β‐estradiol from marine sediment samples with high adsorption capacity, excellent clean‐up efficiency, and great enrichment effect as well as high recovery (>90%) and accuracy (RSD < 8.5%, n = 3). It proved the successful grafting of molecularly imprinted polymers on SiO2 surface and the applicability of the offline molecularly imprinted solid‐phase extraction method in the selective extraction and enrichment of β‐estradiol from marine sediment.
Alternative journal impact factors in open access publishing
Authors: Xia Jingfeng , Smith Megan P.
Published: August 2018

Very little research has been conducted to investigate new journal impact factors that have emerged to rank open access (OA) journals as an alternative to the Journal Citation Reports and SCImago Journal & Country Rank. The few existing studies have found these metrics misleading. Our study examined the criteria used by these impact factors to see whether they are fake metrics or represent early efforts for developing new standards to advance journal evaluations. We analysed as many available alternative impact factors as possible and discovered that their methodologies were either unreproducible or based on unreliable or opaque criteria. We hope this study will help shed light on the ecosystem of OA publishing and identify both possibly unprofessional behaviours and potential improvements in bibliometric algorithms.
Composite Biomaterials as Long‐Lasting Scaffolds for 3D Bioprinting of Highly Aligned Muscle Tissue
Authors: García‐Lizarribar Andrea , Fernández‐Garibay Xiomara , Velasco‐Mallorquí Ferran , Castaño Albert G. , Samitier Josep , Ramon‐Azcon Javier
Published: August 2018

New biocompatible materials have enabled the direct 3D printing of complex functional living tissues, such as skeletal and cardiac muscle. Gelatinmethacryloyl (GelMA) is a photopolymerizable hydrogel composed of natural gelatin functionalized with methacrylic anhydride. However, it is difficult to obtain a single hydrogel that meets all the desirable properties for tissue engineering. In particular, GelMA hydrogels lack versatility in their mechanical properties and lasting 3D structures. In this work, a library of composite biomaterials to obtain versatile, lasting, and mechanically tunable scaffolds are presented. Two polysaccharides, alginate and carboxymethyl cellulose chemically functionalized with methacrylic anhydride, and a synthetic material, such as poly(ethylene glycol) diacrylate are combined with GelMA to obtain photopolymerizable hydrogel blends. Physical properties of the obtained composite hydrogels are screened and optimized for the growth and development of skeletal muscle fibers from C2C12 murine cells, and compared with pristine GelMA. All these composites show high resistance to degradation maintaining the 3D structure with high fidelity over several weeks. Altogether, in this study a library of biocompatible novel and totally versatile composite biomaterials are developed and characterized, with tunable mechanical properties that give structure and support myotube formation and alignment.
Branched Poly(ethylene imine)s as Anti‐algal and Anti‐cyanobacterial Agents with Selective Flocculation Behavior to Cyanobacteria over Algae
Authors: Mikula Premysl , Mlnarikova Marie , Takahashi Haruko , Babica Pavel , Kuroda Kenichi , Blaha Ludek , Sovadinova Iva
Published: August 2018

Poly(ethylene imine)s (PEIs) have been widely studied for biomedical applications, including antimicrobial agents against potential human pathogens. The interactions of branched PEIs (B‐PEIs) with environmentally relevant microorganisms whose uncontrolled growth in natural or engineered environments causes health, economic, and technical issues in many sectors of water management are studied. B‐PEIs are shown to be potent antimicrobials effective in controlling the growth of environmentally relevant algae and cyanobacteria with dual‐functionality and selectivity. Not only did they effectively inhibit growth of both algae and cyanobacteria, mostly without causing cell death (static activity), but they also selectively flocculated cyanobacteria over algae. Thus, unmodified B‐PEIs provide a cost‐effective and chemically facile framework for the further development of effective and selective antimicrobial agents useful for control of growth and separation of algae and cyanobacteria in natural or engineered environments.