bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-conflict household structures and underweight: a multilevel analysis of a community-based study in northern Uganda
Authors: Schramm Stine , Nielsen Jannie , Kaducu Felix O , Okumu Ceaser L , Ovuga Emilio , Sodemann Morten 
Published: June 2018

AbstractObjectiveTo examine associations between household-level characteristics and underweight in a post-conflict population.DesignNutritional status of residents in the Gulu Health and Demographic Surveillance Site was obtained during a community-based cross-sectional study, ~6 years after the civil war. Household-level factors included headship, polygamy, household size, child-to-adult ratio, child crowding, living with a stunted or overweight person, deprived area, distance to health centre and socio-economic status. Multilevel logistic regression models examined associations of household and community factors with underweight, calculating OR, corresponding 95 % CI and intraclass correlation coefficients. Effect modification by gender and age was examined by interaction terms and stratified analyses.SettingRural post-conflict area in northern Uganda.SubjectsIn total, 2799 households and 11 312 individuals were included, representing all age groups.ResultsLiving in a female-headed v. male-headed household was associated (OR; 95 % CI) with higher odds for underweight among adult men (2·18; 1·11, 4·27) and girls <5 years (1·51; 0·97, 2·34), but lower odds among adolescent women aged 13–19 years (0·46; 0·22, 0·97). Higher odds was seen for residents living in deprived areas (1·37; 0·97, 1·94), with increasing distance to health services (P-trend <0·05) and among adult men living alone v. living in an average-sized household of seven members (3·23; 1·22, 8·59). Residents living in polygamous households had lower odds for underweight (0·79; 0·65, 0·97).ConclusionsThe gender- and age-specific associations between household-level factors and underweight are likely to reflect local social capital structures. Adapting to these is crucial before implementing health and nutrition interventions.
Natural cyclopeptide RA-V inhibits the NF-κB signaling pathway by targeting TAK1
Authors: Wang Zhe , Zhao Simeng , Song Lihua , Pu Yuzhi , Wang Qiang , Zeng Guangzhi , Liu Xing , Bai Ming , Li Shao , Gao Fabao , Chen Lijuan , Wang Chen , Tan Ninghua 
Published: June 2018

AbstractRubiaceae-type cyclopeptides (RAs) are a type of plant cyclopeptides from theRubiathat have garnered significant attention owing to their unique bicyclic structures and amazing antitumour activities. Our recent work has shown that RAs suppress inflammation and angiogenesis and induce apoptosis. However, the underlying mechanism and targets remained unknown. Nuclear factor κB (NF-κB) signaling pathway plays a critical role in these biological processes, prompting us to investigate whether and how RAs affect this pathway. By screening compound libraries using NF-κB-dependent luciferase reporter, we observed that RA-V is the best NF-κB inhibitor. Further experiments demonstrated that RA-V interrupted the TAK1–TAB2 interaction and targeted TAK1 in this pathway. Moreover, RA-V prevented endotoxin shock and inhibited NF-κB activation and tumor growth in vivo. These findings clarify the mechanism of RA-V on NF-κB pathway and might account for the majority of known bioactivities of RA-V, which will help RA-V develop as new antiinflammatory and antitumour therapies.
MicroRNA-214 promotes hepatic stellate cell activation and liver fibrosis by suppressing Sufu expression
Authors: Ma Liping , Yang Xiaoxue , Wei Rong , Ye Tinghong , Zhou Jian-Kang , Wen Maoyao , Men Ruoting , Li Ping , Dong Biao , Liu Lunxu , Fu Xianghui , Xu Heng , Aqeilan Rami I. , Wei Yu-Quan , Yang Li , Peng Yong 
Published: June 2018

AbstractMicroRNAs (miRNAs) have been demonstrated to modulate cellular processes in the liver. However, the role of miRNAs in liver fibrosis is poorly understood. Because the activation of hepatic stellate cells (HSCs) is a pivotal event in the initiation and progression of hepatic fibrosis, we investigate the differential expression of miRNAs in activated and quiescent rat HSCs by microarray analysis and find that miR-214 (miR-214-3p) is significantly upregulated during HSC activation. Moreover, the robust induction of miR-214 is correlated with liver fibrogenesis in carbon tetrachloride (CCl4)-treated rats and mice, high-fat diet-induced non-alcoholic steatohepatitis in mice, and cirrhosis in humans. We identify that miR-214 expression is driven by the helix–loop–helix transcription factor Twist1 via the E-box element. The increased miR-214 inhibits the expression of suppressor-of-fused homolog (Sufu), a negative regulator of the Hedgehog signaling pathway, thereby contributing to HSC activation to promote the accumulation of fibrous extracellular matrix and the expression of profibrotic genes in HSCs and LX2 cells. Furthermore, miR-214 expression is inversely correlated with the expression of Sufu in clinical cirrhosis samples. To explore the clinical potential of miR-214, we inject antagomiR-214 oligos into mice to induce hepatic fibrosis. The knockdown of miR-214 in vivo enhances Sufu expression and reduces fibrosis marker expression, which ameliorates liver fibrosis in mice. In conclusions, the Twist1-regulated miR-214 promotes the activation of HSC cells through targeting Sufu involved in the Hedgehog pathway and participates in the development of hepatic fibrosis. Hence, the knockdown of miR-214 expression may be a promising therapeutic strategy for liver fibrosis.
LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1
Authors: Shan Yujia , Ma Jia , Pan Yue , Hu Jialei , Liu Bing , Jia Li 
Published: June 2018

AbstractAccumulating evidence suggests long noncoding RNAs (lncRNAs) play an important role in cancer progression. However, the function of lncRNA SNHG7 in colorectal cancer (CRC) remains unclear. In this study, SNHG7 expression was significantly upregulated in CRC tissues, especially in aggressive cases. In accordance, high level of SNHG7 was observed in CRC cell lines compared to normal colon cells. Furthermore, SNHG7 overexpression promoted the proliferation, migration, and invasion of CRC cell lines, while SNHG7 depletion inhibited invasion and cell viability in vitro. Mechanistically, knockdown of SNHG7 inhibited GALNT1 and EMT markers (E-cadherin and Vimentin). Importantly, SNHG7 directly interacted with miR-216b and downregulation of miR-216b reversed efficiently the suppression of GALNT1 induced by SNHG7 siRNA. Moreover, overexpression of SNHG7 significantly enhanced the tumorigenesis and liver metastasis of SW480 cells in vivo. SNHG7 positively regulated GALNT1 level through sponging miR-216b, and played an oncogenic role in CRC progression. Together, our study elucidated the role of SNHG7 as an miRNA sponge in CRC, and shed new light on lncRNA-directed diagnostics and therapeutics in CRC.
miR-129 controls axonal regeneration via regulating insulin-like growth factor-1 in peripheral nerve injury
Authors: Zhu Hui , Xue Chengbin , Yao Min , Wang Hongkui , Zhang Ping , Qian Tianmei , Zhou Songlin , Li Shiying , Yu Bin , Wang Yongjun , Gu Xiaosong 
Published: June 2018

AbstractThe microenvironment of peripheral nerve regeneration consists of multiple neurotrophic factors, adhesion molecules, and extracellular matrix molecules, secreted by unique glial cells in the peripheral nerve system (PNS)-Schwann cell (SCs). Following peripheral nerve injury (PNI), local IGF-1 production is upregulated in SCs and denervated muscle during axonal sprouting and regeneration. Regulation of IGF-1/IGF-1R signaling is considered as a potentially targeted therapy of PNI. We previously identified a group of novel miRNAs in proximal nerve following rat sciatic nerve transection. The present work focused on the role of miR-129 in regulation of IGF-1 signaling after sciatic nerve injury. The temporal change profile of the miR-129 expression was negatively correlated with the IGF-1 expression in proximal nerve stump and dorsal root ganglion (DRG) following sciatic nerve transection. An increased expression of miR-129 inhibited proliferation and migration of SCs, and axonal outgrowth of DRG neurons, which was inversely promoted by silencing of the miR-129 expression. The IGF-1 was identified as one of the multiple target genes of miR-129, which exerted negative regulation of IGF-1 by translational suppression. Moreover, knockdown of IGF-1 attenuated the promoting effects of miR-129 inhibitor on proliferation and migration of SCs, and neurite outgrowth of DRG neurons. Overall, our data indicated that miR-129 own the potential to regulate the proliferation and migration of SCs by targeting IGF-1, providing further insight into the regulatory role of miRNAs in peripheral nerve regeneration. The present work not only provides new insight into miR-129 regulation of peripheral nerve regeneration by robust phenotypic modulation of neural cells, but also opens a novel therapeutic window for PNI by mediating IGF-1 production. Our results may provide further experimental basis for translation of the molecular therapy into the clinic.
Precision therapeutic targeting of human cancer cell motility
Authors: Xu Li , Gordon Ryan , Farmer Rebecca , Pattanayak Abhinandan , Binkowski Andrew , Huang Xiaoke , Avram Michael , Krishna Sankar , Voll Eric , Pavese Janet , Chavez Juan , Bruce James , Mazar Andrew , Nibbs Antoinette , Anderson Wayne , Li Lin , Jovanovic Borko , Pruell Sean , Valsecchi Matias , Francia Giulio , Betori Rick , Scheidt Karl , Bergan Raymond 
Published: June 2018

AbstractIncreased cancer cell motility constitutes a root cause of end organ destruction and mortality, but its complex regulation represents a barrier to precision targeting. We use the unique characteristics of small molecules to probe and selectively modulate cell motility. By coupling efficient chemical synthesis routes to multiple upfront in parallel phenotypic screens, we identify that KBU2046 inhibits cell motility and cell invasion in vitro. Across three different murine models of human prostate and breast cancer, KBU2046 inhibits metastasis, decreases bone destruction, and prolongs survival at nanomolar blood concentrations after oral administration. Comprehensive molecular, cellular and systemic-level assays all support a high level of selectivity. KBU2046 binds chaperone heterocomplexes, selectively alters binding of client proteins that regulate motility, and lacks all the hallmarks of classical chaperone inhibitors, including toxicity. We identify a unique cell motility regulatory mechanism and synthesize a targeted therapeutic, providing a platform to pursue studies in humans.
Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory
Authors: Cohen Samuel M. , Suutari Benjamin , He Xingzhi , Wang Yang , Sanchez Sandrine , Tirko Natasha N. , Mandelberg Nataniel J. , Mullins Caitlin , Zhou Guangjun , Wang Shuqi , Kats Ilona , Salah Alejandro , Tsien Richard W. , Ma Huan 
Published: June 2018

AbstractLearning and memory depend on neuronal plasticity originating at the synapse and requiring nuclear gene expression to persist. However, how synapse-to-nucleus communication supports long-term plasticity and behavior has remained elusive. Among cytonuclear signaling proteins, γCaMKII stands out in its ability to rapidly shuttle Ca2+/CaM to the nucleus and thus activate CREB-dependent transcription. Here we show that elimination of γCaMKII prevents activity-dependent expression of key genes (BDNF, c-Fos, Arc), inhibits persistent synaptic strengthening, and impairs spatial memory in vivo. Deletion of γCaMKII in adult excitatory neurons exerts similar effects. A point mutation in γCaMKII, previously uncovered in a case of intellectual disability, selectively disrupts CaM sequestration and CaM shuttling. Remarkably, this mutation is sufficient to disrupt gene expression and spatial learning in vivo. Thus, this specific form of cytonuclear signaling plays a key role in learning and memory and contributes to neuropsychiatric disease.
Coupling of electrochemically triggered thermal and mechanical effects to aggravate failure in a layered cathode
Authors: Yan Pengfei , Zheng Jianming , Chen Tianwu , Luo Langli , Jiang Yuyuan , Wang Kuan , Sui Manling , Zhang Ji-Guang , Zhang Sulin , Wang Chongmin 
Published: June 2018

AbstractElectrochemically driven functioning of a battery inevitably induces thermal and mechanical effects, which in turn couple with the electrochemical effect and collectively govern the performance of the battery. However, such a coupling effect, whether favorable or detrimental, has never been explicitly elucidated. Here we use in situ transmission electron microscopy to demonstrate such a coupling effect. We discover that thermally perturbating delithiated LiNi0.6Mn0.2Co0.2O2 will trigger explosive nucleation and propagation of intragranular cracks in the lattice, providing us a unique opportunity to directly visualize the cracking mechanism and dynamics. We reveal that thermal stress associated with electrochemically induced phase inhomogeneity and internal pressure resulting from oxygen release are the primary driving forces for intragranular cracking that resembles a “popcorn” fracture mechanism. The present work reveals that, for battery performance, the intricate coupling of electrochemical, thermal, and mechanical effects will surpass the superposition of individual effects.
Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction
Authors: Zacchigna Serena , Martinelli Valentina , Moimas Silvia , Colliva Andrea , Anzini Marco , Nordio Andrea , Costa Alessia , Rehman Michael , Vodret Simone , Pierro Cristina , Colussi Giulia , Zentilin Lorena , Gutierrez Maria Ines , Dirkx Ellen , Long Carlin , Sinagra Gianfranco , Klatzmann David , Giacca Mauro 
Published: June 2018

AbstractCardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infarction results in depressed cardiac function, massive inflammation, and scarce collagen deposition. In contrast, Treg injection reduces infarct size, preserves contractility, and increases the number of proliferating cardiomyocytes. The overexpression of six factors secreted by Tregs (Cst7, Tnfsf11, Il33, Fgl2, Matn2, and Igf2) reproduces the therapeutic effect. In conclusion, Tregs promote fetal and maternal cardiomyocyte proliferation in a paracrine manner and improve the outcome of myocardial infarction.
A microfluidics platform for combinatorial drug screening on cancer biopsies
Authors: Eduati Federica , Utharala Ramesh , Madhavan Dharanija , Neumann Ulf Peter , Longerich Thomas , Cramer Thorsten , Saez-Rodriguez Julio , Merten Christoph A. 
Published: June 2018

AbstractScreening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
Uplift and denudation in the continental area of China linked to climatic effects: evidence from apatite and zircon fission track data
Authors: Qiu Nansheng , Liu Shuai 
Published: June 2018

AbstractApproximately 2284 fission track data were collected to draw a fission track thermotectonic image of the continental area of China. The result exhibits features such that apatite fission track ages increase from the southwestern to eastern and northern continental areas of China. Thermal paths also reveal the different uplift/denudation processes and times between different tectonic units. At the same time, tectonic uplift of the continent has been among the causes of climate change in the continent since the Cenozoic. The uplift of the Qinghai-Tibet Plateau since the Oligocene is the main cause of the formation of the Asian monsoon and inland droughts, and rapid uplift of the Tibet Plateau after the Pliocene has changed the atmospheric circulation. The main period of climate aridity in Central Asia was caused by the rapid uplift of the Tianshan Mountains since the Miocene, and rapid uplift during the Late Miocene to Pliocene intensified the process of aridity. This study provides the first thermotectonic image of uplift and denudation in the continental area of China and provides a new dating of the formation of the Asian monsoon and climate aridity in Central Asia.
NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
Authors: Hasam-Henderson Luisa A. , Gotti Grace C. , Mishto Michele , Klisch Constantin , Gerevich Zoltan , Geiger Jörg R. P. , Kovács Richard 
Published: June 2018

AbstractDysfunction of parvalbumin (PV)-expressing interneurons is thought to underlie the alterations of gamma-band oscillations observed in schizophrenia. Although the pathomechanisms of this disease remain unclear, oxidative stress induced by NMDA receptor (NMDAR) hypofunction and decreased glutathione (GSH) synthesizing capacity have been shown to lead to PV-loss and aberrant oscillatory activity. However, the individual contributions of NMDAR-inhibition and GSH-depletion to the developmental alterations observed in schizophrenia are largely unknown. We therefore investigated each condition in isolation using hippocampal slice cultures wherein interneuron maturation occurs entirely in vitro. Although both treatments caused oxidative stress, NMDAR-inhibition led to an immediate reduction in gamma oscillation frequency and a delayed loss of PV. In contrast, GSH-depletion immediately decreased PV expression and increased power, without affecting frequency. Hence, although disturbances of PV-expression and gamma oscillations coexist in schizophrenia, they can arise from separate pathological processes.
Depth related adaptations in symbiont bearing benthic foraminifera: New insights from a field experiment on Operculina ammonoides
Authors: Oron Shai , Abramovich Sigal , Almogi-Labin Ahuva , Woeger Julia , Erez Jonathan 
Published: June 2018

AbstractLarge benthic foraminifera (LBF) are marine calcifying protists that commonly harbor algae as symbionts. These organisms are major calcium carbonate producers and important contributors to primary production in the photic zones. Light is one of the main known factors limiting their distribution, and species of this group developed specific mechanisms that allow them to occupy different habitats across the light gradient. Operculina ammonoides (Gronovius, 1781) is a planispiral LBF that has two main shell morphotypes, thick involute and flat evolute. Earlier studies suggested morphologic changes with variation in water depth and presumably light. In this study, specimens of the two morphotypes were placed in the laboratory under artificial low light and near the sea floor at depths of 15 m, 30 m, and 45 m in the Gulf of Aqaba-Eilat for 23 days. Differences in growth and symbionts content were evaluated using weight, size, and chlorophyll a. Our results show that O. ammonoides exhibit morphological plasticity when constructing thinner chambers after relocation to low light conditions, and adding more weight per area after relocation to high light conditions. In addition, O. ammonoides exhibited chlorophyll content adaptation to a certain range of light conditions, and evolute specimens that were acclimatized to very low light did not survive relocation to a high light environment, possibly due to photo-oxidative stress.
Development of an electrooculogram-based human-computer interface using involuntary eye movement by spatially rotating sound for communication of locked-in patients
Authors: Kim Do Yeon , Han Chang-Hee , Im Chang-Hwan 
Published: June 2018

AbstractIndividuals who have lost normal pathways for communication need augmentative and alternative communication (AAC) devices. In this study, we propose a new electrooculogram (EOG)-based human-computer interface (HCI) paradigm for AAC that does not require a user’s voluntary eye movement for binary yes/no communication by patients in locked-in state (LIS). The proposed HCI uses a horizontal EOG elicited by involuntary auditory oculogyric reflex, in response to a rotating sound source. In the proposed HCI paradigm, a user was asked to selectively attend to one of two sound sources rotating in directions opposite to each other, based on the user’s intention. The user’s intentions could then be recognised by quantifying EOGs. To validate its performance, a series of experiments was conducted with ten healthy subjects, and two patients with amyotrophic lateral sclerosis (ALS). The online experimental results exhibited high-classification accuracies of 94% in both healthy subjects and ALS patients in cases where decisions were made every six seconds. The ALS patients also participated in a practical yes/no communication experiment with 26 or 30 questions with known answers. The accuracy of the experiments with questionnaires was 94%, demonstrating that our paradigm could constitute an auxiliary AAC system for some LIS patients.
Prognostic Significance of Infarct Size and Location: The Case of Insular Stroke
Authors: Laredo Carlos , Zhao Yashu , Rudilosso Salvatore , Renú Arturo , Pariente José Carlos , Chamorro Ángel , Urra Xabier 
Published: June 2018

AbstractThe prognostic relevance of strokes in different locations is debated. For example, insular strokes have been associated with increased mortality, but this association could reflect their greater severity. In two independent cohorts of patients with supratentorial ischemic stroke (n = 90 and 105), we studied the prognostic consequences of lesion size and location using voxel-based lesion-symptom mapping before and after volume control, which better accounts for total lesion volume. Strokes affecting the insula were larger than non-insular strokes (28 vs 2cc and 25 vs 3cc, p < 0.001 in both cohorts). A number of supratentorial areas (mainly in the left hemisphere), including the insula, were associated with poor functional outcome in both cohorts before (4014 voxels) and after volume control (1378 voxels), while the associations with death were greatly reduced after volume control (from 8716 to 325 voxels). Exploratory analyses suggested that the method of lesion volume quantification, the National Institutes of Health Stroke Scale hemispheric bias and patient selection can result in false associations between specific brain lesions and outcomes. In conclusion, death in the first months after stroke is mainly explained by large infarct volumes, whereas lesions of specific supratentorial structures, mostly in the left hemisphere, also contribute to poor functional outcomes.