bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Globular Cluster in the Area of VVVX
Authors: Bica E. , Minniti D. , Bonatto C. , Hempel M.
Published: June 2018

We communicate the discovery of a new globular cluster in the Galaxy that was first detected on WISE/2MASS images and is now confirmed with VVVX photometry. It is a Palomar-like cluster projected at ℓ = 359.15°, b = 5.73°, and may be related to the bulge. We derive an absolute magnitude of MV ≈ −3.3, thus being an underluminous globular cluster. Our analyses provide a reddening of E(B − V) = 1.08 ± 0.18 and a distance to the Sun d⊙ = 6.3 ± 1 kpc, which implies a current position in the bulge volume. The estimated metallicity is [Fe/H] = −1.5 ± 0.25. It adds to the recently discovered faint globular cluster (Minniti 22) and candidates found with VVV, building up expectations of ≈50 globular clusters yet to be discovered in the bulge. We also communicate the discovery of an old open cluster in the same VVVX tile as the globular cluster. The VVVX photometry provided E(B − V) = 0.62 ± 0.1, d⊙ = 7.6 ± 1 kpc, and an age of 1.5 ± 0.3 Gyr. With a height from the plane of ≈0.8 kpc, it adds to nine Gyr-class clusters recently discovered within 0.8 ⩽ Z ⩽ 2.2 kpc, as recently probed in the single VVV tile b201. We suggest that these findings may be disclosing the thick disk at the bulge, which so far has no open cluster counterpart, and hardly any individual star. Thus, the VVV and VVVX surveys are opening new windows for follow-up studies, to employ present and future generations of large aperture telescopes.
Early weaning and high feeding level in post-weaning period did not impact milk production in Alpine dairy goats
Authors: Panzuti Clémence , Mandrile Gaëlle , Duvaux-Ponter Christine , Dessauge Frédéric
Published: June 2018

The experiment reported in this Research Communication aimed to determine the combined effects of early weaning and post-weaning feeding level on growth, reproductive parameters and milk yield in Alpine goats. Sixty-four Alpine goat kids were weaned abruptly at either 12·2 (±1·40) kg (40 d of age, E) or 17·7 (±2·30) kg (60 d of age, No). After weaning, E and No goats were subjected to 2 feeding strategies (n = 16): ad libitum concentrate until 130 d of age and then 620 g DM/d/goat until 200 d of age (EC and NoC) or ad libitum concentrate until 200 d of age (EAL and NoAL). Goats were weighed twice a month until 200 d of age. Pregnancy rate and litter size were recorded. Daily milk yield was measured by milk meter during the first lactation. Up to 60 d of age, average daily gain (ADG) of E kids was significantly lower than No kids. From 60 to 130 d of age, ADG of the four treatments were not different. After 130 d of age, EC and NoC kids had lower ADG than EAL and NoAL kids. Pregnancy rates of EAL and NoAL goats were lower than those of EC and NoC. Milk yield was not modified by weaning weight or feeding management. Milk quality was not affected by any treatment. To conclude, the age at weaning as well as the feeding level after weaning did not negatively impact growth and milk yield. We hypothesise that the establishment of the lactation function is not impacted by rearing management. Hence, decreasing the age at weaning could be an interesting way to reduce the cost of the rearing period in goat kids.
Endoscopic push-through technique compared to microscopic underlay myringoplasty in anterior tympanic membrane perforations
Authors: El-Hennawi D E M , Ahmed M R , Abou-Halawa A S , Al-Hamtary M A
Published: June 2018

Background

Microscopic myringoplasty is the most frequently performed procedure for repairing tympanic membrane perforations. The endoscopic transcanal approach bypasses the narrow ear canal segment and provides a wider view.

Methods

An open-label randomised clinical trial was conducted on 56 patients with small anterior tympanic membrane perforations. Perforations were repaired with an endoscopic push-through technique (n= 28) or a microscopic underlay technique (n= 28). Follow up was conducted using endoscopic examination and pure tone audiometry three months’ post-operatively.

Results

Graft success rate was 92.9 per cent in the endoscopic group versus 85.7 per cent in the microscopic group. The corresponding pre-operative mean air–bone gaps were 17.4 dB and 18.5 dB, improving to 6.1 dB and 9.3 dB post-operatively (p> 0.05). Mean air–bone gap closure was 11.4 dB in the endoscopic group and 9.2 dB in the microscopic group (p> 0.05). Mean operative time and estimated blood loss were 37.0 minutes and 29 ml in the endoscopic group, versus 107 minutes and 153 ml in the microscopic group (bothp< 0.05).

Conclusion

The endoscopic push-through technique for anterior tympanic membrane perforations is as effective as microscopic underlay myringoplasty; furthermore, it is less invasive and takes less operative time.
Longitudinal analysis of the audiological phenotype in osteogenesis imperfecta: a follow-up study
Authors: Martens S , Dhooge I J M , Swinnen F K R
Published: June 2018

Objective

This prospective study involved a longitudinal analysis of the progression of hearing thresholds in patients with osteogenesis imperfecta.

Methods

Audiometric results from 36 osteogenesis imperfecta patients (age range, 6–79 years) were compared between two test times with an average interval of 4 years. Audiometric evaluation included acoustic admittance measurements, acoustic stapedial reflex measurements, pure tone audiometry and otoacoustic emissions testing.

Results

Air conduction pure tone average, corrected for sex and age, and bone conduction pure tone average increased significantly in the study population (p < 0.05 and p < 0.001, respectively). In 14.3 per cent of the evaluated ears, an alteration in type and/or severity of hearing loss was observed.

Conclusion

After an average time interval of four years, significant changes in hearing status occurred in a population of osteogenesis imperfecta patients. These findings highlight the importance of regular audiological follow up in osteogenesis imperfecta patients, including audiometry, and measurements of acoustic admittance, acoustic stapedial reflexes and otoacoustic emissions.
From (Violent) Protest to Policy: Rearticulating authority through the National Youth Policy in post-war Nepal
Authors: SNELLINGER AMANDA
Published: June 2018

Youth frustration was a front-running issue during Nepal's decade-long civil war (1996–2006) and democratic protests (2003–2006). Young activists were mobilized as foot soldiers in these political battles, but they also capitalized on their position to establish themselves politically. They earned public recognition for their direct action; however, they have struggled to stay relevant as their parties shifted from protesting against the government to running the government. In response, youth activists leveraged the public support they earned and general concern over youth disenfranchisement to demand an active role in state restructuring. The Maoist-majority Constituent Assembly government partially heeded them by handing over the task of drafting the National Youth Policy to their youth wings and other youth activists. This policy shaped the youth-focused agenda of the newly designed Ministry of Youth and Sports and other government bureaus. This article uses the National Youth Policy as the context for an examination of how youth activists are establishing public authority beyond (violent) protest. By focusing on the micro-politics of the committee appointed to draft the Policy, I analyse the techniques its members used to assert their political values and agendas through policymaking in order to secure their positions during politically turbulent times. This article elucidates how formalized governing practices and revolutionary politics blend to reconstitute state order in the aftermath of civil war.
More than just statics: temporal dynamics of intrinsic brain activity predicts the suicidal ideation in depressed patients
Authors: Li Jiao , Duan Xujun , Cui Qian , Chen Huafu , Liao Wei
Published: June 2018

Background

Major depressive disorder (MDD) is associated with high risk of suicide. Conventional neuroimaging works showed abnormalities of static brain activity and connectivity in MDD with suicidal ideation (SI). However, little is known regarding alterations of brain dynamics. More broadly, it remains unclear whether temporal dynamics of the brain activity could predict the prognosis of SI.

Methods

We included MDD patients (n = 48) with and without SI and age-, gender-, and education-matched healthy controls (n = 30) who underwent resting-state functional magnetic resonance imaging. We first assessed dynamic amplitude of low-frequency fluctuation (dALFF) – a proxy for intrinsic brain activity (iBA) – using sliding-window analysis. Furthermore, the temporal variability (dynamics) of iBA was quantified as the variance of dALFF over time. In addition, the prediction of the severity of SI from temporal variability was conducted using a general linear model.

Results

Compared with MDD without SI, the SI group showed decreased brain dynamics (less temporal variability) in the dorsal anterior cingulate cortex, the left orbital frontal cortex, the left inferior temporal gyrus, and the left hippocampus. Importantly, these temporal variabilities could be used to predict the severity of SI (r = 0.43, p = 0.03), whereas static ALFF could not in the current data set.

Conclusions

These findings suggest that alterations of temporal variability in regions involved in executive and emotional processing are associated with SI in MDD patients. This novel predictive model using the dynamics of iBA could be useful in developing neuromarkers for clinical applications.
Fundamentality and the prior probability of theism
Authors: WILSON LUKE
Published: June 2018

Paul Draper has recently developed an account of intrinsic probability according to which a theory's intrinsic probability is determined by its modesty and coherence. He employs this account in an argument that Source Physicalism (SP) and Source Idealism (SI) are equally intrinsically probable. Since SP and SI are not exhaustive, and Theism is one very specific version of SI, it follows that the intrinsic probability of Theism is very low. I argue here that considerations of fundamentality show that more work needs to be done to defend the claim that P(SP) = P(SI).
What is the Relationship between Benefit Conditionality and Mental Health? Evidence from the United States on TANF Policies
Authors: DAVIS OWEN
Published: June 2018

This article provides new evidence on the relationship between benefit conditionality and mental health. Using data on Temporary Assistance for Needy Families policies (TANF) – the main form of poverty relief in the United States – it explores whether the mental health of low-educated single mothers varies according to the stringency of conditionality requirements attached to receipt of benefit. Specifically, the article combines state-level data on sanctioning practices, work requirements and welfare-to-work spending with health data from the Behavioral Risk Factor Surveillance System and evaluates the impact of conditionality on mental health over a fifteen-year period (2000 to 2015). It finds that states that have harsher sanctions, stricter job search requirements and higher expenditure on welfare-to-work policies, have worse mental health among low-educated single mothers. There is also evidence that between-wave increases in the stringency of conditionality requirements are associated with deteriorations in mental health among the recipient population. It is suggested that these findings may reflect an overall effect of ‘intensive conditionality’, rather than of the individual variables per se. The article ends by considering the wider implications for policy and research.
Acquired but Unvested Welfare Rights: Migration and Entitlement Barriers in Reform-Era China
Authors: Zhang Li , Li Meng
Published: June 2018

Scholars studying Chinese development have long acknowledged the significance of the hukou system in impeding internal migration and defining welfare entitlements. However, another crucial barrier is often overlooked: the incomplete transferability of acquired welfare rights. By examining the case of the Urban Employee Basic Pension System, this paper aims to understand how the limited transferability of acquired rights acts as an obstacle to labour migration and entitlement accomplishment. It also seeks to explore the factors that are accountable for the low level of welfare rights transferability. Our findings suggest that migration and entitlement barriers today may not be so much a question of a particular form of hukou exclusion but more of a problem of insufficient rights portability. An in-depth understanding of the structural constraints of China's reform-era migration and rights attainment needs to take into account the transferability of welfare entitlements for migrant workers, and go beyond a narrow conceptualization of the hukou system per se.
Against Anonymous Pareto
Authors: FISH ERAN
Published: June 2018

The principle known as ‘anonymous Pareto’ has it that an alternative A is better than another, B, in case it is (strictly, non-anonymously) Pareto superior to either B or a permutation of it. It is an attractive idea, offering to apply Pareto-based judgments to a broader range of cases while preserving some of the intuitive appeal of the standard, more familiar principle. This essay considers some ways in which anonymous Pareto is defended and argues against each separately, as well as in more general lines. It suggests that the reasons in light of which people find strict Pareto so compelling are the reasons for doubting the anonymous variation of that principle.
RICARDO AND RICARDIANS ON THE ORDER OF CULTIVATION
Authors: Bidard Christian
Published: June 2018

The Ricardian dynamics are based on the study of the order of cultivation when demand increases. Piero Sraffa criticized David Ricardo for having assumed that the incoming method is defined by a natural order, and stressed that the law of succession of methods is based on a profitability criterion. Then, in the case of intensive cultivation, the question is whether the incoming method is indeed more productive than the one it replaces. Sraffa’s argument relies on the positivity of rent. However, there is a flaw in his reasoning, and a failure of the Ricardian dynamics is possible. Post-Sraffian scholars have misunderstood that construction and have substituted a static approach for it. The critiques they address to Sraffa are better understood by returning to Ricardo and Sraffa’s own methodology. Fifty years ago, mathematicians rediscovered Ricardo’s approach independently and worked out a powerful algorithm inspired by it.
EUGENICS AND SOCIALIST THOUGHT IN THE PROGRESSIVE ERA: THE CASE OF JAMES MEDBERY MACKAYE
Authors: Fiorito Luca , Foresti Tiziana
Published: June 2018

The aim of this essay is to assess James Medbery MacKaye’s contribution to socialist thought during the Progressive Era. Largely forgotten today, MacKaye proposed a special version of socialism, which he called “Pantocracy,” based on a peculiar blend of utilitarian and eugenic assumptions. Specifically, MacKaye held that biological fitness mapped to the capacity for happiness—biologically superior individuals possess a greater capacity for happiness—and saw the eugenic breeding of “a being or race of beings capable in the first place of happiness” as a possibility open by the advent of Pantocracy. Incidentally, this essay provides further evidence that the influence of eugenic and racialist beliefs upon the American Progressive Era political economy was so deep-rooted and pervasive that it did cut across traditional ideological boundaries.
Bilingual exposure enhances left IFG specialization for language in children
Authors: ARREDONDO MARIA M. , HU XIAO-SU , SEIFERT ERICA , SATTERFIELD TERESA , KOVELMAN IOULIA
Published: June 2018

Language acquisition is characterized by progressive use of inflectional morphology marking verb tense and agreement. Linguistic milestones are also linked to left-brain lateralization for language specialization. We used neuroimaging (fNIRS) to investigate how bilingual exposure influences children's cortical organization for processing morpho-syntax. In Study 1, monolinguals and bilinguals (n = 39) completed a grammaticality judgment task that included English sentences with violations in earlier-acquired (verb agreement) and later-acquired (verb tense/agreement) structures. Groups showed similar performance and greater activation in left inferior frontal region (IFG) for later- than earlier-acquired conditions. Bilinguals showed stronger and more restricted left IFG activation. In Study 2, bilinguals completed a comparable Spanish task revealing patterns of left IFG activation similar to English. Taken together, the findings suggest that bilinguals with linguistic competence at parity with monolingual counterparts have a higher degree of cortical specialization for language, likely a result of enriched linguistic experiences.
The bilingual mental lexicon beyond Dutch–English written words
Authors: GORAL MIRA
Published: June 2018

The contribution that Ton Dijkstra has made to the field of bilingualism, with his colleagues over the years, is beyond measure. He has advanced our field with the thoughtful and thought-provoking models of the bilingual lexicon he has put forward, and with the vast empirical data he and his colleagues have collected from numerous bilinguals, using a variety of experimental methods. This paper by Dijkstra, Wahl, Buytenhuijs, van Halem, Al-jibouri, de Korte, and Rekké (2018) is no exception. It comprises a thoughtful and detailed description of a new model, Multilink, and provides relevant information regarding the context in which the model was developed, its assumptions, its successes and challenges. The model is the first to consider aspects of both word production and word recognition, as well as of word translation, and to explicitly address how translation equivalents that share both form and meaning – cognates – may be processed. Also addressed are word-frequency concerns, including differences in word frequency that are dependent on language proficiency and exposure. The assumptions that are made within the model are clearly laid out, and less-than-ideal decisions that needed to be made are acknowledged. The authors conclude that a model like Multilink could be the basis for a general model of the mental lexicon. In that, they promote the view taken in Libben, Goral, and Libben (2017) that the bilingual – not the monolingual – lexicon should be considered as the default.
Prevalence and risk factor analysis of iron deficiency and iron-deficiency anaemia among female adolescents in the Gaza Strip, Palestine
Authors: Jalambo Marwan O , Karim Norimah A , Naser Ihab A , Sharif Razinah
Published: June 2018

Objective

The present study aimed to determine the prevalence of anaemia, iron deficiency (ID) and iron-deficiency anaemia (IDA) among female adolescents in the Gaza Strip, Palestine, as well as the risk factors involved in these conditions.

Design

The study was conducted using the quantitative descriptive method with a cross-sectional design. Data were collected using an FFQ and sociodemographic, sedentary behaviour and physical activity questionnaires. Anthropometric measurements and blood analyses were also conducted.

Setting

The study population included all Palestinian female adolescents enrolled in secondary schools in the academic years 2015–2016. Five female secondary schools were selected randomly from five governorates of the Gaza Strip.

Subjects

Female adolescents (n330) aged 15–19 years in the selected secondary schools were enrolled randomly.

Results

Prevalence of anaemia, ID and IDA among female adolescents in the Gaza Strip, Palestine, was 35·8, 40·3 and 26·0 %, respectively. A significant association (P<0·05) existed between ID, anaemia and IDA and dietary habits, including skipping breakfast and amount of junk food intake. Also, low consumption of fruits and vegetables was associated with IDA in the female adolescents. A statistically significant association was found between mother’s education and ID but not with the other sociodemographic factors.

Conclusions

The study shows that there is an alarming problem of anaemia and IDA in the Gaza Strip, Palestine. This may indicate that there are insufficient nutrition education programmes, particularly inside schools or by the mass media.
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

Objective

To examine associations between household-level characteristics and underweight in a post-conflict population.

Design

Nutritional 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.

Setting

Rural post-conflict area in northern Uganda.

Subjects

In total, 2799 households and 11 312 individuals were included, representing all age groups.

Results

Living 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).

Conclusions

The 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.
Phänomenologie, Diagnostik und Behandlung von Halluzinationen
Authors: Hubl Daniela
Published: June 2018

Zusammenfassung. Halluzinationen sind Wahrnehmungen ohne einen adäquaten Stimulus. Sie treten typischerweise bei der schizophrenen Psychose auf, können aber auch Symptom bei anderen psychiatrischen oder medizinischen Erkrankungen sein. Zunehmend versteht man Fehlwahrnehmungen sogar im Sinne eines Kontinuums zwischen Gesunden und Kranken. Halluzinationen können in allen Sinnesmodalitäten auftreten und je nach Semiologie diagnostisch hilfreich sein. In besonderer Weise haben die schizophrenen akustischen Halluzinationen klar die Nähe zur Sprache und sind wegweisendes diagnostisches Merkmal. Die Neuroanatomie der Stimmen zeigt, dass beim Stimmenhörer Hirngebiete ursächlich beteiligt sind, die beim Gesunden für Hören, Sprechen und Verstehen verantwortlich sind – sogar unabhängig von der Ätiologie. Neben der Standardtherapie des Stimmenhörens, die aus der Gabe von Antipsychotika besteht, werden bei Therapieresistenz vermehrt Hirnstimulationsmethoden eingesetzt und hier vorgestellt. Allen voran die repetitive transkranielle Magnetstimulation (rTMS) und transkranielle Gleichstrombehandlung (tDCS), wobei die rTMS ihren Platz in der Therapie von resistenten Halluzinationen bereits gefunden hat. Auf jeden Fall haben sich diese Methoden zur Behandlung und weiteren Erforschung von Halluzinationen in der universitären Forschung etabliert.
Neue Konzepte klinischer Diagnostik
Authors: Petermann Franz
Published: June 2018

Zusammenfassung. Lange Jahre hatte vor allem die psychometrische Diagnostik im Bereich der Psychotherapie und Psychiatrie eine Außenseiterrolle inne. Dieser Zustand ändert sich schrittweise, wobei einige neuere Trends dies begünstigen. Die Bedeutung von Entwicklungsmodellen psychischer Störungen, und damit prämorbider Strukturen im Rahmen der Entstehung psychischer Störungen, ist dabei besonders hervorzuheben. Zudem veränderten die Fortschritte der Klinischen Neuropsychologie allmählich die Rolle der klinischen Diagnostik. In dieser Situation kommt dem Konzept „Evidence-based-Assessment“ eine wichtige Rolle zu.
Temperament in der frühen Kindheit und die Entwicklung externalisierender Störungen: Implikationen für die klinische Diagnostik
Authors: Kiel Natalie , Bruckdorfer Raphaela , Petermann Franz , Reinelt Tilman
Published: June 2018

Zusammenfassung. Der vorliegende Beitrag legt Zusammenhänge zwischen Temperament in der frühen Kindheit und der Entstehung externalisierender Störungen im weiteren Entwicklungsverlauf dar. Dafür erfolgte eine eingehende Recherche über Temperament und dessen Erfassung im Alter von 0 bis 6 Jahren sowie über die prognostische Validität entsprechender Erhebungsinstrumente. Es wurde untersucht, inwiefern Temperamentsfragebögen in der klinischen Praxis diagnostisch genutzt werden können. Es zeigte sich, dass bestimmte Temperamentsmerkmale, die von verschiedenen theoretischen Modellen eingeschlossen werden, einen Beitrag zur Vorhersage der Entwicklung externalisierender Störungen leisten. Bereits in den ersten Lebensmonaten können Temperamentsmerkmale erhoben und prognostisch genutzt werden. Temperamentsbezogene Elternfragebögen können die Diagnostik zum aktuellen Zeitpunkt zwar sinnvoll ergänzen, liegen zum Teil allerdings nicht für den deutschsprachigen Raum vor und weisen mitunter psychometrische und praktische Unzulänglichkeiten auf.
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

Rubiaceae-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

MicroRNAs (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

Accumulating 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

The 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

Increased 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

Learning 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

Electrochemically 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

Cardiomyocyte 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

Screening 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.
Author Correction: Loss of the adaptor protein ShcA in endothelial cells protects against monocyte macrophage adhesion, LDL-oxydation, and atherosclerotic lesion formation
Authors: Abou-Jaoude Antoine , Badiqué Lise , Mlih Mohamed , Awan Sara , Guo Sunning , Lemle Alexandre , Abboud Clauda , Foppolo Sophie , Host Lionel , Terrand Jérôme , Justiniano Hélène , Herz Joachim , Matz Rachel L. , Boucher Philippe
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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

Approximately 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

Dysfunction 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

Large 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

Individuals 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

The 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.