bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of Human Dance: Courtship, Rites of Passage, Trance, Calendrical Ceremonies and the Professional Dancer
Authors: Garfinkel Yosef
Published: February 2018

A model of five major chronological phases is suggested for the history of human dance. These phases did not replace one another, but accumulated as successive layers. The earliest phase is associated with courtship, thus explaining the potent role of dance in sexual desire and seduction. The second phase is associated with the appearance of modern human behaviour and the earliest burials, which were rites of passage that involved the first communal dances. The third phase is associated with the appearance of hybrid human-animal figurines that point to altered states of consciousness and aspirations to change reality; this is when trance dance, shamanism, magic and religion came in. The fourth phase is connected with the beginning of agriculture in Neolithic villages, which was coordinated by elaborate calendrical ceremonies. The fifth and final phase is associated with urban societies, economic complexity and specialization; well-trained professional dancers now performed acrobatic body movements and elaborate choreography for the enjoyment of others. The history of dance thus reflects the history of human rituals and religion.
Post-Patent Ductus Arteriosus ligation syndrome with hypertension and masking of renal artery stenosis in an infant
Authors: ElSeed Peterson Erica E. , Mauriello Daniel
Published: February 2018

Post-patent ductus arteriosus ligation syndrome is common, but rarely has hypertension been described following ductal ligation with an unclear mechanism. We report a case of an infant who exhibited features of post-patent ductus arteriosus ligation syndrome and hypertension, but was found to have bilateral renal artery stenosis. Increased systemic vascular resistance can be masked by the parallel circuit physiology of a patent ductus arteriosus.
Percutaneous retrieval of a partially flared Melody valve
Authors: Gendera Katarzyna , Ewert Peter , Eicken Andreas
Published: February 2018

We report on successful endovascular retrieval of an accidentally flared Melody valve in an adult patient with an indication for percutaneous pulmonary valve implantation. The Melody valve was removed through a 24 F sheath, introduced via the right jugular vein, and the urgent open-heart surgery was avoided.
AESTHETIC RISK
Authors: Pritchard Duncan
Published: February 2018

Artists often emphasize the importance of risk to their work. But this raises a puzzle, as on a standard probabilistic account of risk we are obliged to treat some of these cases as not involving genuine risk at all. It is argued that the way to resolve this puzzle is to recognize a crucial shortcoming in the probabilistic account of risk. With this shortcoming rectified, and hence with a revised modal account of risk in place, we are able to treat the relevant cases of putative aesthetic risk as entirely genuine.
WHATEVER HAPPENED TO WISDOM?
Authors: Hill Euan
Published: February 2018

Philosophy, by no longer performing its original therapeutic function of helping people to become wise, choosing instead to offer analysis, has left us at risk of losing the techniques which had evolved to facilitate the task of teaching wisdom throughout its history. In the process of endeavouring to re-establish Philosophy as Therapy after the war, with the aim of helping people to think for themselves rather than just study the ideas of others, Wittgenstein and Wisdom rediscovered the need for many of these techniques, especially for a way of revealing to people their underlying and unconscious assumptions.
Effects of Incorporated Rye and Hairy Vetch Cover Crop Residue on the Persistence of Weed Seeds in the Soil
Authors: Mohler Charles L. , Taylor Alan G. , DiTommaso Antonio , Hahn Russell R. , Bellinder Robin R.
Published: February 2018

Incorporation of cover crop residue into the soil has been suggested as a means for reducing weed seedbanks. To explore this hypothesis, we buried mesh bags of seeds mixed with sand at 15-cm depth in late fall in plots that had been planted with rye (Secale cerealeL.) or hairy vetch (Vicia villosaRoth.) or left unplanted. Separate bags contained either velvetleaf (Abutilon theophrastiMedik.), giant foxtail (Setaria faberiHerrm.), Powell amaranth (Amaranthus powelliiS. Watson), or common lambsquarters (Chenopodium albumL.). The experiment used a randomized complete block design with five replications, and enough bags were buried to allow a final recovery in each of the following three springs. Each spring, bags were exhumed, and seeds were either counted and tested for viability or mixed with chopped cover crop material or simply stirred for control bags, and the material was reburied. The experiment was completed twice with initial burials in fall of 2011 and 2013. Rye had no consistent effect on persistence of seeds of any of the species. For two observation intervals, rye increased persistence of a species; for another two intervals, it decreased persistence relative to the control; but mostly rye did not affect persistence. Hairy vetch decreased persistence ofC. albumandA. powelliiin both runs of the experiment but had no effect on persistence ofA. theophrastiandS. faberi. Germination of the first two species is promoted by nitrate, whereasA. theophrastigermination is not sensitive to nitrate, andS. faberiis only rarely nitrate sensitive. We suggest that nitrate released during decomposition of hairy vetch may have promoted fatal germination ofC. albumandA. powellii. Incorporation of legume cover crops like hairy vetch may provide a means for decreasing the seedbanks of the many weed species whose germination is promoted by nitrate. The lack of any reduction ofA. theophrastiandS. faberiseed persistence in response to hairy vetch and the inconsistent and mostly negligible effect of rye indicate that a general increase in readily decomposable organic matter through incorporation of cover crops may be ineffective at reducing weed seedbanks.
Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1β production
Authors: Tang Anthony C , Rahavi Seyed M , Fung Shan-Yu , Lu Henry Y , Yang Hong , Lim Chinten J , Reid Gregor S , Turvey Stuart E
Published: February 2018

Proteasome inhibitors have emerged as an effective therapy for the treatment of haematological malignancies; however, their efficacy can be limited by the development of tumour resistance mechanisms. Novel combination strategies including the addition of TLR adjuvants to increase cell death and augment immune responses may help enhance their effectiveness. Although generally thought to inhibit inflammatory responses and NF-κB activation, we found that under specific conditions proteasome inhibitors can promote inflammatory responses by mediating IL-1β maturation and secretion after TLR stimulation. This was dependent on the timing of proteasome inhibition relative to TLR stimulation where reversal of treatment order could alternatively increase or inhibit IL-1β secretion (P < 0.001). TLR stimulation combined with proteasome inhibition enhanced cell death in vitro and delayed tumour development in vivo in NOD SCID mice (P < 0.01). However, unlike IL-1β secretion, cell death occurred similarly regardless of treatment order and was only partially caspase dependent, possessing characteristics of both apoptosis and necrosis as indicated by activation of caspase-1, 3, 8 and RIP3 phosphorylation. Although stimulation of various TLRs was capable of driving IL-1β production, TLR4 stimulation was the most effective at increasing cell death in THP-1 and U937 cells. TLR4 stimulation and proteasome inhibition independently activated the RIP3 necroptotic pathway and ultimately reduced the effectiveness of caspase/necroptosis inhibitors in mitigating overall levels of cell death. This strategy of combining TLR stimulation with proteasome inhibition may improve the ability of proteasome inhibitors to generate immunogenic cell death and increase anti-tumour activity.
Photosensitization of A2E triggers telomere dysfunction and accelerates retinal pigment epithelium senescence
Authors: Wang Jing , Feng Yiji , Han Peng , Wang Fenghua , Luo Xueting , Liang Jian , Sun Xiangjun , Ye Jing , Lu Yiming , Sun Xiaodong
Published: February 2018

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in elderly people. AMD is classified as early, intermediate, advanced non-neovascular, and advanced neovascular forms depending on the clinical features. However, the exact pathogenesis remains unclear. Retinal pigment epithelium (RPE) cells degeneration is a hallmark of AMD. With aging, lipofuscin accumulates in RPE cells. N-retinylidene-N-retinylethanolamine (named A2E), a well-known fluorophore of lipofuscin, may contribute to RPE cells degeneration. In this study, we showed that photosensitization of A2E increased DNA damage, including telomere deprotection and deletion, and triggered cellular senescence. In addition, we found that the antioxidant N-acetyl-cysteine (NAC) partially alleviated this DNA damage. Telomerase overexpression rescued A2E-mediated RPE cell senescence, indicating that telomere dysfunction plays an important role in A2E-based senescence. We further showed that the senescence induced by A2E photosensitization may affect the microenvironment of the retina by expressing several factors of the secretory phenotype (SASP) including IL1B, IL13RA2, and CXCR4 through the NF-κB pathway. We propose that expression of these factors create a pro-inflammatory environment that drives retina degeneration. Moreover, our findings suggest that protecting telomeres is a valuable strategy for treating retinal degeneration diseases, such as AMD.
PDE5 inhibition eliminates cancer stem cells via induction of PKA signaling
Authors: Klutzny Saskia , Anurin Anna , Nicke Barbara , Regan Joseph L. , Lange Martin , Schulze Luise , Parczyk Karsten , Steigemann Patrick
Published: February 2018

Cancer stem cells (CSCs) are involved in metastasis and resistance development, thus affecting anticancer therapy efficacy. The underlying pathways required for CSC maintenance and survival are not fully understood and only a limited number of treatment strategies to specifically target CSCs have been identified. To identify novel CSC targeting compounds, we here set-up an aldehyde dehydrogenase (ALDH)-based phenotypic screening system that allows for an automated and standardized identification of CSCs. By staining cancer cells for ALDH activity and applying high-content-based single-cell population analysis, the proportion of a potential CSC subpopulation with significantly higher ALDH activity (ALDHhigh) can be quantified in a heterogeneous cell population. We confirmed high ALDH activity as surrogate marker for the CSC subpopulationin vitroand validated Wnt signaling as an essential factor for the maintenance of CSCs in SUM149 breast cancer cells. In a small molecule screen, we identified phosphodiesterase type 5 (PDE5) inhibition as potential strategy to target CSC maintenance and survival in multiple cancer cell lines. CSC elimination by PDE5 inhibition was not dependent on PKG signaling, and we suggest a novel mechanism in which PDE5 inhibition leads to elevated cGMP levels that stimulate cAMP/PKA signaling to eliminate CSCs.
LanCL1 protects prostate cancer cells from oxidative stress via suppression of JNK pathway
Authors: Wang Jianqing , Xiao Qianyi , Chen Xu , Tong Shijun , Sun Jianliang , Lv Ruitu , Wang Siqing , Gou Yuancheng , Tan Li , Xu Jianfeng , Fan Caibin , Ding Guanxiong
Published: February 2018

Prostate cancer (PCa) is the most commonly diagnosed malignancy in male. Numerous studies have focused on the molecular mechanisms of carcinogenesis and progression, aiming at developing new therapeutic strategies. Here we describe Lanthionine synthase C-like protein 1 (LanCL1), a member of the LanCL family, is a potential prostate cancer susceptibility gene. LanCL1 promotes prostate cancer cell proliferation and helps protect cells from damage caused by oxidative stress. Suppression of LanCL1 by siRNA results in increased cancer cell apoptosis. Clinical data also indicate that LanCL1 upregulation in human prostate cancers correlates with tumor progression. Finally, we demonstrate that LanCL1 plays such important role through inhibiting JNK pathway. Altogether, our results suggest that LanCL1 protects cells from oxidative stress, and promotes cell proliferation. LanCL1 reduces cell death via suppression of JNK signaling pathway.
bFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats
Authors: Sun Dawei , Wang Wenying , Wang Xintao , Wang Yan , Xu Xiaotao , Ping Feng , Du Yu , Jiang Wei , Cui Derong
Published: February 2018

Transient global cerebral ischemia (tGCI) is a cerebrovascular disorder that can cause apoptotic neuronal damage and functional deficits. Basic fibroblast growth factor (bFGF) was reported to be highly expressed in the central nervous system (CNS) and to exert neuroprotective effects against different CNS diseases. However, the effects of bFGF on tGCI have not been studied intensively. This study was conducted to investigate the effect of bFGF and its underlying mechanism in an animal model of tGCI. After intracerebroventricular (i.c.v.) injection of bFGF, functional improvement was observed, and the number of viable neurons increased in the ischemia-vulnerable hippocampal CA1 region. Apoptosis was induced after tGCI and could be attenuated by bFGF treatment via inhibition of p53 mitochondrial translocation. In addition, autophagy was activated during this process, and bFGF could inhibit activation of autophagy through the mTOR pathway. Rapamycin, an activator of autophagy, was utilized to explore the relationship among bFGF, apoptosis, and autophagy. Apoptosis deteriorated after rapamycin treatment, which indicated that excessive autophagy could contribute to the apoptosis process. In conclusion, these results demonstrate that bFGF could exert neuroprotective effects in the hippocampal CA1 region by suppressing excessive autophagy via the mTOR pathway and inhibiting apoptosis by preventing p53 mitochondrial translocation. Furthermore, our results suggest that bFGF may be a promising therapeutic agent to for treating tGCI in response to major adverse events, including cardiac arrest, shock, extracorporeal circulation, traumatic hemorrhage, and asphyxiation.
Genome-wide DNA methylation analysis reveals that mouse chemical iPSCs have closer epigenetic features to mESCs than OSKM-integrated iPSCs
Authors: Ping Wangfang , Hu Jian , Hu Gongcheng , Song Yawei , Xia Qing , Yao Mingze , Gong Shixin , Jiang Cizhong , Yao Hongjie
Published: February 2018

Abstract

Induced pluripotent stem cells can be derived from somatic cells through ectopic expression of transcription factors or chemical cocktails. Chemical iPSCs (C-iPSCs) and OSKM-iPSCs (4F-iPSCs) have been suggested to have similar characteristics to mouse embryonic stem cells (mESCs). However, their epigenetic equivalence remains incompletely understood throughout the genome. In this study, we have generated mouse C-iPSCs and 4F-iPSCs, and further compared the genome-wide DNA methylomes of C-iPSCs, 4F-iPSCs, and mESCs that were maintained in 2i and LIF. Three pluripotent stem cells tend to be low methylated overall, however, DNA methylations in some specific regions (such as retrotransposons) are cell type-specific. Importantly, C-iPSCs are more hypomethylated than 4F-iPSCs. Bisulfite sequencing indicated that DNA methylation status in several known imprinted clusters, such as: Dlk1-Dio3 and Peg12-Ube3a, in C-iPSCs are closer to those of mESCs than 4F-iPSCs. Overall, our data demonstrate the reprogramming methods-dependent epigenetic differences of C-iPSCs and 4F-iPSCs and reveal that C-iPSCs are more hypomethylated than OSKM-integrated iPSCs.
MicroRNA-27a-5p regulation by promoter methylation and MYC signaling in prostate carcinogenesis
Authors: Barros-Silva Daniela , Costa-Pinheiro Pedro , Duarte Henrique , Sousa Elsa Joana , Evangelista Adriane Feijó , Graça Inês , Carneiro Isa , Martins Ana Teresa , Oliveira Jorge , Carvalho André L. , Marques Márcia M. , Henrique Rui , Jerónimo Carmen
Published: February 2018

Upregulation of MYC and miRNAs deregulation are common in prostate cancer (PCa). Overactive MYC may cause miRNAs’ expression deregulation through transcriptional and post-transcriptional mechanisms and epigenetic alterations are also involved in miRNAs dysregulation. Herein, we aimed to elucidate the role of regulatory network between MYC and miRNAs in prostate carcinogenesis. MYC expression was found upregulated in PCa cases and matched precursor lesions. MicroRNA’s microarray analysis of PCa samples with opposed MYC levels identified miRNAs significantly overexpressed in high-MYC PCa. However, validation of miR-27a-5p in primary prostate tissues disclosed downregulation in PCa, instead, correlating with aberrant promoter methylation. In a series of castration-resistant PCa (CRPC) cases, miR-27a-5p was upregulated, along with promoter hypomethylation. MYC and miR-27a-5p expression levels in LNCaP and PC3 cells mirrored those observed in hormone-naíve PCa and CRPC, respectively. ChIP analysis showed that miR-27a-5p expression is only regulated by c-Myc in the absence of aberrant promoter methylation. MiR-27a-5p knockdown in PC3 cells promoted cell growth, whereas miRNA forced expression in LNCaP and stable MYC-knockdown PC3 cells attenuated the malignant phenotype, suggesting a tumor suppressive role for miR-27a-5p. Furthermore, miR-27a-5p upregulation decreased EGFR/Akt1/mTOR signaling. We concluded that miR-27a-5p is positively regulated by MYC, and its silencing due to aberrant promoter methylation occurs early in prostate carcinogenesis, concomitantly with loss of MYC regulatory activity. Our results further suggest that along PCa progression, miR-27a-5p promoter becomes hypomethylated, allowing for MYC to resume its regulatory activity. However, the altered cellular context averts miR-27a-5p from successfully accomplishing its tumor suppressive function at this stage of disease.
LncRNA NCK1-AS1 promotes proliferation and induces cell cycle progression by crosstalk NCK1-AS1/miR-6857/CDK1 pathway
Authors: Li Haiyu , Jia Yongqin , Cheng Junning , Liu Geli , Song Fangzhou
Published: February 2018

The purpose of this study was to develop an lncRNA signature to improve the prediction of the prognosis of cervical cancer through integration bioinformatics and analysis of TCGA RNA sequencing data. In this study, we established a set of four lncRNA signatures that was significantly associated with recurrence-free survival using the Cox regression model. Functionally, we screened the CC-associated lncRNA NCK1-AS1 as a new candidate lncRNA and regulator which promotes development and progression in CC. qRT-PCR and RNA in situ hybridization (RISH) results showed that NCK1-AS1 was significantly up-regulated in 77.4% (24/31) of the CC tissue group compared with the normal group (P < 0.01). Interestingly, we demonstrated that transcription factor SP1 directly binds to the promoter to activate NCK1-AS1 expression in SiHa cells. In vitro and in vivo assays of silencing NCK1-AS1 significantly inhibited cell proliferation and invasion, with induction of cell arrest in S phase of the cell cycle. Furthermore, Human Transcriptome Array 2.0 analysis after NCK1-AS1 silencing highlighted alterations in cell proliferation and cell cycle pathways. NCK1-AS1 functioned as a molecular sponge for miR-6857, antagonizing its ability to repress CDK1/6 protein translation. In conclusion, these findings suggest that NCK1-AS1/miR-6857/CDK1 crosstalk serve as a critical effector in cervical cancer progression and may serve as a potential target in cervical cancer.
Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death
Authors: Thellung Stefano , Scoti Beatrice , Corsaro Alessandro , Villa Valentina , Nizzari Mario , Gagliani Maria Cristina , Porcile Carola , Russo Claudio , Pagano Aldo , Tacchetti Carlo , Cortese Katia , Florio Tullio
Published: February 2018

According to the “gain-of-toxicity mechanism”, neuronal loss during cerebral proteinopathies is caused by accumulation of aggregation-prone conformers of misfolded cellular proteins, although it is still debated which aggregation state actually corresponds to the neurotoxic entity. Autophagy, originally described as a variant of programmed cell death, is now emerging as a crucial mechanism for cell survival in response to a variety of cell stressors, including nutrient deprivation, damage of cytoplasmic organelles, or accumulation of misfolded proteins. Impairment of autophagic flux in neurons often associates with neurodegeneration during cerebral amyloidosis, suggesting a role in clearing neurons from aggregation-prone misfolded proteins. Thus, autophagy may represent a target for innovative therapies. In this work, we show that alterations of autophagy progression occur in neurons following in vitro exposure to the amyloidogenic and neurotoxic prion protein-derived peptide PrP90-231. We report that the increase of autophagic flux represents a strategy adopted by neurons to survive the intracellular accumulation of misfolded PrP90-231. In particular, PrP90-231 internalization in A1 murine mesencephalic neurons occurs in acidic structures, showing electron microscopy hallmarks of autophagosomes and autophagolysosomes. However, these structures do not undergo resolution and accumulate in cytosol, suggesting that, in the presence of PrP90-231, autophagy is activated but its progression is impaired; the inability to clear PrP90-231 via autophagy induces cytotoxicity, causing impairment of lysosomal integrity and cytosolic diffusion of hydrolytic enzymes. Conversely, the induction of autophagy by pharmacological  blockade of mTOR kinase or trophic factor deprivation restored autophagy resolution, reducing intracellular PrP90-231 accumulation and neuronal death. Taken together, these data indicate that PrP90-231 internalization induces an autophagic defensive response in A1 neurons, although incomplete and insufficient to grant survival; the pharmacological enhancement of this process exerts neuroprotection favoring the clearing of the internalized peptide and could represents a promising neuroprotective tool for neurodegenerative proteinopathies.
miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma
Authors: Jin Yun-Peng , Hu Yun-Ping , Wu Xiang-Song , Wu Yao-Shi , Ye Yuan-Yuan , Li Huai-Feng , Liu Yong-Chen , Jiang Lin , Liu Fa-Tao , Zhang Yi-Jian , Hao Ya-Juan , Liu Xi-Yong , Liu Ying-Bin
Published: February 2018

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary track system. Angiogenesis plays a pivotal role in the development and progression of malignant tumours. miR-143-3p acts as a tumour suppressor in various cancers. Their role in GBC is however less well defined. Here we show that the expression levels of miR-143-3p were decreased in human GBC tissues compared with the non-tumour adjacent tissue (NAT) counterparts and were closely associated with overall survival. We discovered that miR-143-3p was a novel inhibitor of tumour growth and angiogenesis in vivo and in vitro. Our antibody array, ELISA and PLGF rescue analyses indicated that PLGF played an essential role in the antiangiogenic effect of miR-143-3p. Furthermore, we used miRNA target-prediction software and dual-luciferase assays to confirm that integrin α6 (ITGA6) acted as a direct target of miR-143-3p. Our ELISA and western blot analyses confirmed that the expression of PLGF was decreased via the ITGA6/PI3K/AKT pathway. In conclusion, miR-143-3p suppresses tumour angiogenesis and growth of GBC through the ITGA6/PI3K/AKT/PLGF pathways and may be a novel molecular therapeutic target for GBC.
NF-κB inhibition by dimethylaminoparthenolide radiosensitizes non-small-cell lung carcinoma by blocking DNA double-strand break repair
Authors: Deraska Peter V. , O’Leary Colin , Reavis Hunter D. , Labe Shelby , Dinh Tru-Khang , Lazaro Jean-Bernard , Sweeney Christopher , D’Andrea Alan D. , Kozono David
Published: February 2018

Despite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization. Here we demonstrate that inhibition of the canonical NF-κB pathway by dimethylaminoparthenolide (DMAPT) radiosensitizes NSCLC by blocking DNA double-strand break (DSB) repair. NF-κB inhibition results in significant impairment of both homologous recombination (HR) and non-homologous end joining (NHEJ), as well as reductions in ionizing radiation (IR)-induced DNA repair biomarkers. NF-κB inhibition by DMAPT shows preclinical potential for further investigation as a NSCLC radiosensitizer.
Lithium induces mesenchymal-epithelial differentiation during human kidney development by activation of the Wnt signalling system
Authors: Price Karen L. , Kolatsi-Joannou Maria , Mari Chiara , Long David A. , Winyard Paul J. D.
Published: February 2018

Kidney function is directly linked to the number of nephrons which are generated until 32–36 weeks gestation in humans. Failure to make nephrons during development leads to congenital renal malformations, whilst nephron loss in adulthood occurs in progressive renal disease. Therefore, an understanding of the molecular processes which underlie human nephron development may help design new treatments for renal disease. Mesenchyme to epithelial transition (MET) is critical for forming nephrons, and molecular pathways which control rodent MET have been identified. However, we do not know whether they are relevant in human kidney development. In this study, we isolated mesenchymal cell lines derived from human first trimester kidneys in monolayer culture and investigated their differentiation potential. We found that the mesenchymal cells could convert into osteogenic, but not adipogenic or endothelial lineages. Furthermore, addition of lithium chloride led to MET which was accompanied by increases in epithelial (CDH1) and tubular (ENPEP) markers and downregulation of renal progenitor (SIX2, EYA1, CD133) and mesenchymal markers (HGF, CD24). Prior to phenotypic changes, lithium chloride altered Wnt signalling with elevations in AXIN2, GSK3β phosphorylation and β-catenin. Collectively, these studies provide the first evidence that lithium-induced Wnt activation causes MET in human kidneys. Therapies targeting Wnts may be critical in the quest to regenerate nephrons for human renal diseases.
Ecology and genomics of an important crop wild relative as a prelude to agricultural innovation
Authors: von Wettberg Eric J.B. , Chang Peter L. , Başdemir Fatma , Carrasquila-Garcia Noelia , Korbu Lijalem Balcha , Moenga Susan M. , Bedada Gashaw , Greenlon Alex , Moriuchi Ken S. , Singh Vasantika , Cordeiro Matilde A. , Noujdina Nina V. , Dinegde Kassaye Negash , Shah Sani Syed Gul Abbas , Getahun Tsegaye , Vance Lisa , Bergmann Emily , Lindsay Donna , Mamo Bullo Erena , Warschefsky Emily J. , Dacosta-Calheiros Emmanuel , Marques Edward , Yilmaz Mustafa Abdullah , Cakmak Ahmet , Rose Janna , Migneault Andrew , Krieg Christopher P. , Saylak Sevgi , Temel Hamdi , Friesen Maren L. , Siler Eleanor , Akhmetov Zhaslan , Ozcelik Huseyin , Kholova Jana , Can Canan , Gaur Pooran , Yildirim Mehmet , Sharma Hari , Vadez Vincent , Tesfaye Kassahun , Woldemedhin Asnake Fikre , Tar’an Bunyamin , Aydogan Abdulkadir , Bukun Bekir , Penmetsa R. Varma , Berger Jens , Kahraman Abdullah , Nuzhdin Sergey V. , Cook Douglas R.
Published: February 2018

Domesticated species are impacted in unintended ways during domestication and breeding. Changes in the nature and intensity of selection impart genetic drift, reduce diversity, and increase the frequency of deleterious alleles. Such outcomes constrain our ability to expand the cultivation of crops into environments that differ from those under which domestication occurred. We address this need in chickpea, an important pulse legume, by harnessing the diversity of wild crop relatives. We document an extreme domestication-related genetic bottleneck and decipher the genetic history of wild populations. We provide evidence of ancestral adaptations for seed coat color crypsis, estimate the impact of environment on genetic structure and trait values, and demonstrate variation between wild and cultivated accessions for agronomic properties. A resource of genotyped, association mapping progeny functionally links the wild and cultivated gene pools and is an essential resource chickpea for improvement, while our methods inform collection of other wild crop progenitor species.
Understanding the plume dynamics of explosive super-eruptions
Authors: Costa Antonio , J. Suzuki Yujiro , Koyaguchi Takehiro
Published: February 2018

Explosive super-eruptions can erupt up to thousands of km3 of magma with extremely high mass flow rates (MFR). The plume dynamics of these super-eruptions are still poorly understood. To understand the processes operating in these plumes we used a fluid-dynamical model to simulate what happens at a range of MFR, from values generating intense Plinian columns, as did the 1991 Pinatubo eruption, to upper end-members resulting in co-ignimbrite plumes like Toba super-eruption. Here, we show that simple extrapolations of integral models for Plinian columns to those of super-eruption plumes are not valid and their dynamics diverge from current ideas of how volcanic plumes operate. The different regimes of air entrainment lead to different shaped plumes. For the upper end-members can generate local up-lifts above the main plume (over-plumes). These over-plumes can extend up to the mesosphere. Injecting volatiles into such heights would amplify their impact on Earth climate and ecosystems.
Author Correction: Midbrain circuit regulation of individual alcohol drinking behaviors in mice
Authors: Juarez Barbara , Morel Carole , Ku Stacy M. , Liu Yutong , Zhang Hongxing , Montgomery Sarah , Gregoire Hilledna , Ribeiro Efrain , Crumiller Marshall , Roman-Ortiz Ciorana , Walsh Jessica J. , Jackson Kelcy , Croote Denise E. , Zhu Yingbo , Zhang Song , Vendruscolo Leandro F. , Edwards Scott , Roberts Amanda , Hodes Georgia E. , Lu Yongke , Calipari Erin S. , Chaudhury Dipesh , Friedman Allyson K. , Han Ming-Hu
Published: February 2018

The original version of this Article contained an error in the spelling of the author Scott Edwards, which was incorrectly given as Scott Edward. This has now been corrected in both the PDF and HTML versions of the Article.
Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging
Authors: Oh Gabriel , Ebrahimi Sasha , Carlucci Matthew , Zhang Aiping , Nair Akhil , Groot Daniel E. , Labrie Viviane , Jia Peixin , Oh Edward S. , Jeremian Richie H. , Susic Miki , Shrestha Tenjin C. , Ralph Martin R. , Gordevičius Juozas , Koncevičius Karolis , Petronis Art
Published: February 2018

Circadian rhythmicity governs a remarkable array of fundamental biological functions and is mediated by cyclical transcriptomic and proteomic activities. Epigenetic factors are also involved in this circadian machinery; however, despite extensive efforts, detection and characterization of circadian cytosine modifications at the nucleotide level have remained elusive. In this study, we report that a large proportion of epigenetically variable cytosines show a circadian pattern in their modification status in mice. Importantly, the cytosines with circadian epigenetic oscillations significantly overlap with the cytosines exhibiting age-related changes in their modification status. Our findings suggest that evolutionary advantageous processes such as circadian rhythmicity can also contribute to an organism’s deterioration.
Publisher Correction: Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway
Authors: Li Jianshuang , Lu Di , Dou Hong , Liu Huadie , Weaver Kevin , Wang Wenjun , Li Jiada , Yeh Edward T. H. , Williams Bart O. , Zheng Ling , Yang Tao
Published: February 2018

In the originally published version of this Article, the positions of the final two authors in the author list were inadvertently inverted during the production process. This error has now been corrected in both the PDF and HTML versions of the Article.
Effects of diversity in olfactory environment on children’s sense of smell
Authors: Martinec Nováková Lenka , Fialová Jitka , Havlíček Jan
Published: February 2018

Diversity in children’s everyday olfactory environment may affect the development of their olfactory abilities and odor awareness. To test this, we collected data on olfactory abilities using the Sniffin’ Sticks and odor awareness with Children’s Olfactory Behaviors in Everyday Life Questionnaire in 153 preschool children and retested them one and a half year later. Parents completed an inventory on children’s exposure to a variety of odors and on their own odor awareness using the Odor Awareness Scale. We controlled for the effects of age and verbal fluency on the children’s performance. We found that the children’s odor identification and discrimination scores differed as a function of parental odor awareness. Although these effects were rather small, they were commensurate in size with those of gender and age. To the best of our knowledge, this study is the first to present evidence that diversity in children’s olfactory environment affects variation in their olfactory abilities and odor awareness. We suggest that future studies consider the long-term impact of perceptual learning out of the laboratory and its consequences for olfactory development.
Abnormal optical anisotropy in correlated disorder KTa1−xNbxO3:Cu with refractive index gradient
Authors: Zhang Xin , He Shan , Zhao Zhuan , Wu Pengfei , Wang Xuping , Liu Hongliang
Published: February 2018

In this report, an abnormal optical anisotropy in KTa1−xNbxO3:Cu (Cu:KTN) crystals with refractive index gradient is presented. Contrary to general regulation in a cross-polarization setup, the transmitted intensity of both TE (horizontally polarized) and TM (vertically polarized) lasers aligned with the basic crystallographic directions can be modulated quasiperiodically. The mechanism is supposed to be based on the polarization induced by the temperature gradient and the refractive index gradient. Meanwhile, the correlated disorder property of the crystals in the range of the freezing temperature (Tf) and the intermediate temperature (T *) also plays an important role. With the results verified both theoretically and experimentally, we believe this work is not only beneficial for the development of the theory associated with the correlated disorder structures in relaxor ferroelectrics, but also significant for the exploitation of numerous optical functional devices.
Concise N-doped Carbon Nanosheets/Vanadium Nitride Nanoparticles Materials via Intercalative Polymerization for Supercapacitors
Authors: Tan Yongtao , Liu Ying , Tang Zhenghua , Wang Zhe , Kong Lingbin , Kang Long , Liu Zhen , Ran Fen
Published: February 2018

N-doped carbon nanosheets/vanadium nitride nanoparticles (N-CNS/VNNPs) are synthesized via a novel method combining surface-initiated in-situ intercalative polymerization and thermal-treatment process in NH3/N2 atmosphere. The pH value of the synthesis system plays a critical role in constructing the structure and enhancing electrochemical performance for N-CNS/VNNPs, which are characterized by SEM, TEM, XRD, and XPS, and measured by electrochemical station, respectively. The results show that N-CNS/VNNPs materials consist of 2D N-doped carbon nanosheets and 0D VN nanoparticles. With the pH value decreasing from 2 to 0, the sizes of both carbon nanosheets and VN nanoparticles decreased to smaller in nanoscale. The maximum specific capacitance of 280 F g−1 at the current density of 1 A g−1 for N-CNS/VNNPs is achieved in three-electrode configuration. The asymmetric energy device of Ni(OH)2||N-CNS/VNNPs offers a specific capacitance of 89.6 F g−1 and retention of 60% at 2.7 A g−1 after 5000 cycles. The maximum energy density of Ni(OH)2 ||N-CNS/VNNPs asymmetric energy device is as high as 29.5 Wh kg−1.
Vascular dysfunction in obese diabetic db/db mice involves the interplay between aldosterone/mineralocorticoid receptor and Rho kinase signaling
Authors: Nguyen Dinh Cat Aurelie , Callera Glaucia E. , Friederich-Persson Malou , Sanchez Ana , Dulak-Lis Maria Gabriela , Tsiropoulou Sofia , Montezano Augusto C. , He Ying , Briones Ana M. , Jaisser Frederic , Touyz Rhian M.
Published: February 2018

Activation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+. This was associated with enhanced vascular MR signaling. Norepinephrine (NE)-induced contraction was increased in arteries from db/db mice. These responses were attenuated in mice treated with canrenoate or fasudil. Db/db mice displayed hypertrophic remodeling and increased arterial stiffness, improved by MR blockade. Vascular calcium sensitivity was similar between depolarized arteries from db/+ and db/db. Vascular hypercontractility in db/db mice was associated with increased myosin light chain phosphorylation and reduced expression of PKG-1α. Vascular RhoA/ROCK signaling and expression of pro-inflammatory and pro-fibrotic markers were exaggerated in db/db mice, effects that were attenuated by MRA. Fasudil, but not MRA, improved vascular insulin sensitivity in db/db mice, evidenced by normalization of Irs1 phosphorylation. Our data identify novel pathways involving MR-RhoA/ROCK-PKG-1 that underlie vascular dysfunction and injury in diabetic mice.
Rpb9-deficient cells are defective in DNA damage response and require histone H3 acetylation for survival
Authors: Sein Henel , Reinmets Kristina , Peil Kadri , Kristjuhan Kersti , Värv Signe , Kristjuhan Arnold
Published: February 2018

Rpb9 is a non-essential subunit of RNA polymerase II that is involved in DNA transcription and repair. In budding yeast, deletion of RPB9 causes several phenotypes such as slow growth and temperature sensitivity. We found that simultaneous mutation of multiple N-terminal lysines within histone H3 was lethal in rpb9Δ cells. Our results indicate that hypoacetylation of H3 leads to inefficient repair of DNA double-strand breaks, while activation of the DNA damage checkpoint regulators γH2A and Rad53 is suppressed in Rpb9-deficient cells. Combination of H3 hypoacetylation with the loss of Rpb9 leads to genomic instability, aberrant segregation of chromosomes in mitosis, and eventually to cell death. These results indicate that H3 acetylation becomes essential for efficient DNA repair and cell survival if a DNA damage checkpoint is defective.
Combined aptamer and transcriptome sequencing of single cells
Authors: Delley Cyrille L. , Liu Leqian , Sarhan Maen F. , Abate Adam R.
Published: February 2018

The transcriptome and proteome encode distinct information that is important for characterizing heterogeneous biological systems. We demonstrate a method to simultaneously characterize the transcriptomes and proteomes of single cells at high throughput using aptamer probes and droplet-based single cell sequencing. With our method, we differentiate distinct cell types based on aptamer surface binding and gene expression patterns. Aptamers provide advantages over antibodies for single cell protein characterization, including rapid, in vitro, and high-purity generation via SELEX, and the ability to amplify and detect them with PCR and sequencing.
LINC01088 inhibits tumorigenesis of ovarian epithelial cells by targeting miR-24-1-5p
Authors: Zhang Weijiang , Fei Jing , Yu Shuqian , Shen Jiayu , Zhu Xiaoqing , Sadhukhan Annapurna , Lu Weiguo , Zhou Jianwei
Published: February 2018

The roles of long non-coding RNAs (lncRNAs), a class of long non-protein-coding RNAs, in the tumorigenesis of ovarian epithelial cells remain unknown. In this study, we discovered that the expression of long intergenic non-coding RNA 1088 (LINC01088) was clearly reduced in benign epithelial ovarian tumor tissues compared to matched normal ovarian tissues. This was shown by global cDNA gene chip scanning and real-time qPCR, and validated in 42 clinical specimens. Furthermore, we found that LINC01088 inhibited the growth of ovarian cancer xenografts in nude mice. Correlation analysis between LINC01088 and mircoRNAs (miRNAs) conducted using primary clinical samples and RNA co-precipitation experiments revealed that miR-24-1-5p was one of the targets of LINC01088. Overexpression of miR-24-1-5p facilitated cell proliferation both in vitro and in vivo, however, LINC01088 could partially reverse the cell proliferation induced by miR-24-1-5p. Finally, we demonstrated that p21 activated kinase 4 (PAK4) was one of the downstream key targets of miR-24-1-5p by luciferase reporter assay and Western blotting; and our results showed a remarkable decrease in cell proliferation after overexpression of PAK4. We conclude that LINC01088 might function as a tumor suppressor, inhibiting the tumorigenesis of ovarian epithelial cells through LINC01088/ miR-24-1-5p/ PAK4 axis.
Age-related changes in the response of retinal structure, function and blood flow to pressure modification in rats
Authors: Zhao Da , Nguyen Christine T. O. , He Zheng , Wong Vickie H. Y. , van Koeverden Anna K. , Vingrys Algis J. , Bui Bang V.
Published: February 2018

Age-related changes to the balance between the pressure inside the eye (intraocular pressure, IOP) and the pressure inside the brain (intracranial pressure, ICP) can modify the risk of glaucoma. In this study, we consider whether the optic nerve in older rat eyes is more susceptible to acute IOP and ICP modification. We systematically manipulate both ICP and IOP and quantify their effects on ganglion cell function (electroretinography, ERG), optic nerve structure (optical coherence tomography, OCT) and retinal blood flow (Doppler OCT). We show that ganglion cell function in older eyes was more susceptible to a higher optic nerve pressure difference (ONPD = IOP – ICP). This age-related susceptibility could not be explained by poorer blood flow with elevated ONPD. Rather, as ONPD increased the retinal nerve fibre layer showed greater compression, and the retinal surface showed less deformation in older eyes. Our data suggest that age-related changes to connective tissues in and around the rat optic nerve make it less flexible, which may result in greater strain on ganglion cell axons. This may account for greater functional susceptibility to higher optic nerve pressure differences in older rat eyes. Further studies in a species with a well-developed lamina cribrosa are needed to determine the clinical importance of these observations.
One-step noninvasive prenatal testing (NIPT) for autosomal recessive homozygous point mutations using digital PCR
Authors: Chang Mun Young , Ahn Soyeon , Kim Min Young , Han Jin Hee , Park Hye-Rim , Seo Han Kyu , Yoon Jinsun , Lee Seungmin , Oh Doo-Yi , Kang Changsoo , Choi Byung Yoon
Published: February 2018

Previously, we introduced a noninvasive prenatal testing (NIPT) protocol for diagnosing compound heterozygous autosomal recessive point mutations via maternal plasma DNA and simulated control genomic DNA sampling based on fetal DNA fraction. In our present study, we have improved our NIPT protocol to make it possible to diagnose homozygous autosomal recessive point mutations without the need to acquire fetal DNA fraction. Moreover, chi-squared test and empirical statistical range based on the proportion of mutant allele reads among the total reads served as the gatekeeping method. If this method yielded inconclusive results, then the Bayesian method was performed; final conclusion was drawn from the results of both methods. This protocol was applied to three families co-segregating congenital sensorineural hearing loss with monogenic homozygous mutations in prevalent deafness genes. This protocol successfully predicted the fetal genotypes from all families without the information about fetal DNA fraction using one-step dPCR reactions at least for these three families. Furthermore, we suspect that confirmatory diagnosis under this protocol is possible, not only by using picodroplet dPCR, but also by using the more readily available chip-based dPCR, making our NIPT protocol more useful in the diagnosis of autosomal recessive point mutations in the future.
Repercussion of Solid state vs. Liquid state synthesized p-n heterojunction RGO-copper phosphate on proton reduction potential in water
Authors: Samal Alaka , Das Dipti P. , Madras Giridhar
Published: February 2018

The same copper phosphate catalysts were synthesized by obtaining the methods involving solid state as well as liquid state reactions in this work. And then the optimised p-n hybrid junction photocatalysts have been synthesized following the same solid/liquid reaction pathways. The synthesized copper phosphate photocatalyst has unique rod, flower, caramel-treat-like morphology. The Mott-Schottky behavior is in accordance with the expected behavior of n-type semiconductor and the carrier concentration was calculated using the M-S analysis for the photocatalyst. And for the p-n hybrid junction of 8RGO-Cu3(PO4)2-PA (PA abbreviated for photoassisted synthesis method), 8RGO-Cu3(PO4)2-EG(EG abbreviated for Ethylene Glycol based synthesis method), 8RGO-Cu3(PO4)2-PEG (PEG abbreviated for Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol based synthesis method)the amount of H2 synthesized was 7500, 6500 and 4500 µmol/h/g, respectively. The excited electrons resulting after the irradiation of visible light on the CB of p-type reduced graphene oxide (RGO) migrate easily to n-type Cu3(PO4)2via. the p-n junction interfaces and hence great charge carrier separation was achieved.
Soil-borne fungi challenge the concept of long-term biochemical recalcitrance of pyrochar
Authors: De la Rosa José M. , Miller Ana Z. , Knicker Heike
Published: February 2018

Pyrogenic organic matter (PyOM) is assumed to be biochemically recalcitrant, but recent studies indicated a quick decrease of PyOM in post-fire soils. Regardless erosion and abiotic degradation, microbial decomposition has been the explanation for this response, but no direct proof has been provided up to now. In the present study, we were able to demonstrate for the first time that the soil-borne fungus Fusarium oxysporum is not only colonizing the pore system of pyrochar (PyC) but is also involved in the degradation of its aromatic network. We showed that PyC not only stimulates microbial degradation of soil organic matter (SOM), but is also attacked and decomposed by microorganisms. Our observations are based on the chemical and morphological alterations of a sewage-sludge derived PyC produced at 600 °C after its amendment to a Calcic Cambisol by solid-state 13C nuclear magnetic resonance spectroscopy, analytical pyrolysis, elemental analysis, field emission scanning electron microscopy and DNA-based analysis of the isolated fungi. We showed that biofilms detected in the PyC play an essential role in the degradation process. These results are indispensable for a reliable assessment of the carbon sequestration potential of PyC in soils but also for improving global C cycling models.