bluuebunny/crossref_metadata_2025 huggingface dataset:
Geodesic Flows Modelled by Expansive Flows
Authors: Gelfert Katrin , Ruggiero Rafael O.
Published: August 2018

Given a smooth compact surface without focal points and of higher genus, it is shown that its geodesic flow is semi-conjugate to a continuous expansive flow with a local product structure such that the semi-conjugation preserves time parametrization. It is concluded that the geodesic flow has a unique measure of maximal entropy.
MODEL INSTITUTIONS AND THE GEOGRAPHY OF SOCIAL REFORM IN EARLY VICTORIAN BRITAIN
Authors: CROOK TOM
Published: August 2018

This article reconsiders the nature and novelty of social reform in Britain during the early Victorian period. Historians have long ceased to debate the period in terms of a ‘revolution in government’, or the beginnings of a welfare state. Instead, the current consensus presents a picture of only modest, fitful change. Neither the state, nor the overall ideological landscape, was radically transformed. This article seeks to reinject a sense of transformative change back into these decades. It does so by examining a neglected facet of this otherwise richly served period of social reform: the formation and functioning of a series of self-styled ‘model’ institutions that spanned the fields of education, prisons, housing, and sanitation. In particular, what the use of these model institutions brings into sharp focus are the radical changes that occurred in the geography of social reform, which at this point began to develop according to multiple spatial relations, extending at once within and beyond Britain. Between them, they helped to engineer a truly cosmopolitan culture of social policy-making, which was both multi-directional – policies flowed outwards and inwards – and composed of multiple relations, national, imperial, and transnational.
Proteomic profile associated with cell death induced by androgens in Taenia crassiceps cysticerci: proposed interactome
Authors: Ambrosio J.R. , Palacios-Arreola M.I. , Ríos-Valencia D.G. , Reynoso-Ducoing O. , Nava-Castro K.E. , Ostoa-Saloma P. , Morales-Montor J.
Published: August 2018

Androgens have been shown to exert a cysticidal effect uponTaenia crassiceps, an experimental model of cysticercosis. To further inquire into this matter, theTaenia crassicepsmodel was used to evaluate the expression of several proteins after testosterone (T4) and dihydrotestosterone (DHT)in vitrotreatment. Under 2-D proteomic maps, parasite extracts were resolved into approximately 130 proteins distributed in a molecular weight range of 10–250 kDa and isoelectrical point range of 3–10. The resultant proteomic pattern was analysed, and significant changes were observed in response to T4 and DHT. Based on our experience with electrophoretic patterns and proteomic maps of cytoskeletal proteins, alteration in the expression of isoforms of actin, tubulin and paramyosin and of other proteins was assessed. Considering that androgens may exert their biological activity in taeniids through the non-specific progesterone receptor membrane component (PGRMC), we harnessed bioinformatics to propose the identity of androgen-regulated proteins and establish their hypothetical physiological role in the parasites. These analyses yield a possible explanation of how androgens exert their cysticidal effects through changes in the expression of proteins involved in cytoskeletal rearrangement, dynamic vesicular traffic and transduction of intracellular signals.
Comparative efficacy of ivermectin and Nigella sativa against helminths in Aseel chickens (Gallus gallus domesticus)
Authors: Angel C. , Akhter N. , Arijo A. , Qureshi T.A. , Gandahi J.A. , Qazi I.H.
Published: August 2018

In this study, we evaluated the in vivo comparative efficacy of ivermectin and Nigella sativa extract against helminths in Aseel chickens, and the effects of helminths on blood parameters before and after treatment in Aseel chickens. Forty naturally infected adult Aseel chickens were randomly divided into four groups (n = 10 each): group A (ivermectin at 300 μg/kg); group B (N. sativa extract at 200 mg/kg); group C (ivermectin at 300 μg/kg + N. sativa extract at 200 mg/kg); group D was kept as a positive control to monitor time-related changes. On day 28 post treatment, the mean percentages of faecal egg-count reduction (FECR %) in groups A, B and C were recorded as 93.58, 88.09 and 100.00%, respectively. Further data analysis showed significantly higher efficacy in group C (100 ± 0.00%) than in groups A and B (P < 0.001). Highly significant (P < 0.001) improvements in mean percentage values of packed cell volume (PCV %) were recorded in groups A and C on days 14 and 28 post treatment. Meanwhile, the improvements in mean values of haemoglobin (Hb) concentration in groups A, B and C were highly significant (P < 0.001) when compared to that of group D on day 28 post treatment. The synergistic combination of ivermectin and N. sativa extract possessed greater efficacy than either ivermectin or N. sativa extract used alone. Furthermore, both PCV % and Hb concentration values gradually increased in the treated groups compared to the control group, in which PCV % and Hb concentration gradually decreased throughout the trial.
Patulous nasolacrimal duct with air reflux: a complication of submucosal diathermy of the inferior turbinate
Authors: Puttasiddaiah P M , Whittet C R , Shuttleworth G N
Published: August 2018

Background

Submucosal diathermy to the inferior turbinate is a widely practised procedure to improve the nasal airway when nasal obstruction is due to hypertrophy of the inferior turbinate. This paper reports a case of an unusual nasolacrimal complication following submucosal diathermy to the inferior turbinate, and reviews the relevant literature.

Case report

A 33-year-old male patient developed a patulous nasolacrimal duct opening following submucosal diathermy of the inferior turbinate. This resulted in spontaneous reflux of air and nasal mucus on to the ocular surface.

Conclusion

This newly recognised complication of submucosal diathermy to the inferior turbinate indicates the need to be aware of the potential risk to the nasolacrimal system with this technique.
Asian Plantation Histories at the Frontiers of Nation and Globalization
Authors: MANJAPRA KRIS
Published: August 2018

This is a review article of four new books on plantation histories of Asia which offer a sophisticated analysis of the configurations of liberal imperialism, colonial capitalism, and the construction of post-colonial nationalism in the nineteenth and twentieth centuries. The works discussed here are Rana Behal'sA hundred years of servitude(2014); Jayeeta Sharma'sEmpire's garden(2011); Ulbe Bosma'sThe sugar plantation in India and Indonesia(2013); and Kumari Jayawardena and Rachel Kurian'sClass, patriarchy and ethnicity on Sri Lankan plantations(2015).
Rodents of Senegal and their role as intermediate hosts of Hydatigera spp. (Cestoda: Taeniidae)
Authors: Catalano Stefano , Bâ Khalilou , Diouf Nicolas D. , Léger Elsa , Verocai Guilherme G. , Webster Joanne P.
Published: August 2018

Hydatigera (Cestoda: Taeniidae) is a recently resurrected genus including species seldom investigated in sub-Saharan Africa. We surveyed wild small mammal populations in the areas of Richard Toll and Lake Guiers, Senegal, with the objective to evaluate their potential role as intermediate hosts of larval taeniid stages (i.e. metacestodes). Based on genetic sequences of a segment of the mitochondrial DNA gene cytochrome c oxidase subunit 1 (COI), we identified Hydatigera parva metacestodes in 19 out of 172 (11.0%) Hubert's multimammate mice (Mastomys huberti) and one out of six (16.7%) gerbils (Taterillus sp.) and Hydatigera taeniaeformis sensu stricto metacestodes in one out of 215 (0.5%) Nile rats (Arvicanthis niloticus). This study reports epidemiological and molecular information on H. parva and H. taeniaeformis in West African rodents, further supporting the phylogeographic hypothesis on the African origin of H. parva. Our findings may indicate significant trophic interactions contributing to the local transmission of Hydatigera spp. and other parasites with similar life-cycle mechanisms. We therefore propose that further field investigations of rodent population dynamics and rodent-borne infectious organisms are necessary to improve our understanding of host–parasite associations driving the transmission risks of rodent parasites in West Africa.
The structure of idioms in Nigerian English
Authors: Umar Aliyu Muhammad
Published: August 2018

The term ‘structure in linguistics’ is mostly used to refer to a sequence of units that are in a certain linguistic relationship to one another. Thus no matter how minimal a sequence is, if it can be analysed in terms of a relationship within it, then that is a structural unit. For example, one of the structures of a noun phrase may be ‘article + adjective + noun’ as inthe vicious circle(Richards & Schmidts, 2002). Structures entail relationships which may be syntagmatic or paradigmatic. According to Finnegan (2014) when we say language structure we are essentially talking about syntax, semantics and phonology of a language. When it comes to idioms the same principles apply. The structures of idioms are essentially their syntactic behaviour. This behaviour cannot be predicted solely on the basis of their form or figurative meaning alone, but it must be due to some relation between the form and meaning (Gibbs & Nayak, 1989). An idiom is an institutionalised and conventionalized sequence of at least two words or free morphemes that is semantically restricted so that it functions as a single lexical unit, whose meaning cannot or can only to a certain extent be deduced from the meanings of its constituents. (Skandera, 2003: 60). To Nurnberg, Sag and Wasow (1994), idioms are characterised as having conventional meaning, figuration, inflexibility of form, and proverbiality. Idioms have been called ‘multiword units’ (Grant & Bauer, 2004), metaphors (Gibbs, 1993; Toris, 2011), phrasemes (Howarth, 1998), fixed expressions (Moon, 1997; Carter, 1998) and formulaic expressions (Wray, 2002). Structurally, idioms do not form a unique class of linguistic items such that all idioms belong to it, but that they share many of the same properties normally associated with more literal expressions.
Modern English usage from Britain to America
Authors: Straaijer Robin
Published: August 2018

Garner's Modern English Usage(hereafter Garner4) was published by Oxford University Press USA in 2016. Appearing within a span of two decades, it is the fourth edition of Bryan Garner's dictionary of usage, originally published asA Dictionary of Modern American Usage(Garner, 1998, hereafter Garner1). It is also the second dictionary of English usage to be published during the last three years, following the latest edition of what is arguably its most direct British counterpart,Fowler's Dictionary of Modern English Usage(Butterfield, 2015, hereafter Fowler4).
Mechanical circulatory support using modified TandemHeart ventricular assist device in neonates with CHD
Authors: Chowdhury Shamsur , Chadha Tanya , Fafard Mark , Shillingford Michael
Published: August 2018

TandemHeart, an adult ventricular assist device, is also being used in children for mechanical circulatory support. In this case series, we describe our experience using TandemHeart ventricular assist device with a modified circuit to provide mechanical circulatory support in three neonates for multiple indications. TandemHeart ventricular assist device with a modified circuit can be used successfully to provide extracorporeal support to neonates with complex CHD.
The much-awaited Venezia applicator: virtues of combined intracavitary and interstitial brachytherapy in locally advanced cervical cancer
Authors: Gangopadhyay Aparna , Saha Subrata
Published: August 2018

Locally advanced cervix cancer is a major health problem in resource-limited areas of the world. Brachytherapy following pelvic chemoradiation is challenging, as large irregular clinical target volumes need adequate dose delivery while respecting limits of normal tissue tolerance. Achieving this is practically impossible using intracavitary brachytherapy alone. Consequently, combined intracavitary and interstitial brachytherapy provides higher chances of local control.
The PUFFinCA scale: development of an instrument for evaluating the primary care functions of family physicians in childhood asthma
Authors: Usturali Mut Ayşe Nur , Öcek Zeliha Aslı , Çiçeklioğlu Meltem , Taner Şafak , Demir Esen
Published: August 2018

Aim

To develop the Primary care fUnctions oF Family physicians in Childhood Asthma (PUFFinCA) scale for evaluating the cardinal process functions of primary care services (accessibility, comprehensiveness, continuity and coordination) provided by family physicians (FPs) in the management of childhood asthma.

Background

In the literature on the functions of primary care, there is no assessment tool focusing on children with asthma. Primary care assessment scales adapted to various languages are not suitable to adequately address the needs of special patient groups, such as children with asthma.

Methods

In this methodological study, the instrument development process was completed in four stages: establishing the pool of items, evaluating the content validity, applying the scale and statistical analysis. The scale was applied to 320 children who had asthma and received care in the clinic of the Department of Pediatrics, Division of Allergy and Pulmonology at Ege University School of Medicine, Turkey. The Cronbach’sαand Spearman–Brown coefficient were calculated to determine the reliability of the scale. Principal component analysis was used to determine the construct validity of the scale.

Findings

The PUFFinCA scale was found to have four-factor structure and 25 items. Cronbach’sαcoefficient was 0.93. It has been determined that the reliability was excellent and the item-total correlation coefficients were >0.30 each. The factors were titled FP’s ‘functions of accessibility, first contact and continuity’, ‘functions of coordination and comprehensiveness of health services related to asthma management’, ‘provision of preventive care related to asthma’ and ‘provision of services for paid vaccinations’.
Liquid-crystal-based amplitude tuner and tunable SIW filter fabricated in LTCC technology
Authors: Prasetiadi Ananto E. , Jost Matthias , Schulz Baerbel , Quibeldey Matthias , Rabe Torsten , Follmann Ruediger , Jakoby Rolf
Published: August 2018

Tunable microwave devices will play an important role in future wireless systems, in which high-frequency bands, e.g. millimeter waves, will become promising, due to its huge spectrum availability. At such frequency bands, liquid crystals (LCs) exhibit low microwave loss, which is excellent compared with the other tuning elements. In this paper, LC-based microwave components are fabricated by using low temperature co-fired ceramic technology, allowing the integration of the LC into microwave structures. The first component, the amplitude tuner, controls the signal's amplitude by using the interference concept, which exhibits a tunable attenuation range from 11 dB to 30 dB at 30 GHz. The second component is a 3-pole tunable bandpass filter, which is realized by using a substrate integrated waveguide topology, enabling a device with comparatively high-quality factors (Q-factors). The measurement results show Q-factors in the range of 68 to 100 for a frequency tuning of 29.4–30.1 GHz, i.e. a tuning range of 700 MHz, accompanied by an insertion loss 2 dB to 4 dB.
Reliability analysis of BiCMOS SiGe:C technology under aggressive conditions for emerging RF and mm-wave applications: proposal of reliability-aware circuit design methodology
Authors: Lahbib Insaf , Wane Sidina , Doukkali Aziz , Lesénéchal Dominique , Dinh Thanh Vinh , Leyssenne Laurent , Germanicus Rosine Coq , Bezerra Françoise , Rolland Guy , Andrei Cristian , Imbert Guy , Martin Patrick , Descamps Philippe , Boguszewski Guillaume , Bajon Damienne
Published: August 2018

In this contribution, the impact of extreme environmental conditions in terms of energy-level radiation of protons on silicon–germanium (SiGe)-integrated circuits is experimentally studied. Canonical representative structures including linear (passive interconnects/antennas) and non-linear (low-noise amplifiers) are used as carriers for assessing the impact of aggressive stress conditions on their performances. Perspectives for holistic modeling and characterization approaches accounting for various interaction mechanisms (substrate resistivity variations, couplings/interferences, drift in DC and radio frequency (RF) characteristics) for active samples are down to allow for optimal solutions in pushing SiGe technologies toward applications with harsh and radiation-intense environments (e.g. space, nuclear, military). Specific design prototypes are built for assessing mission-critical profiles for emerging RF and mm-wave applications.
The Neuromodulatory Effects of Sex Hormones on Functional Cerebral Asymmetries and Cognitive Control
Authors: Hodgetts Sophie , Hausmann Markus
Published: August 2018

Abstract. Nearly 20 years ago, Hausmann and Güntürkün (2000a, 2000b) published a review article in the Journal of Neuropsychology/Zeitschrift für Neuropsychologie on the influences of sex hormones on functional cerebral asymmetries (FCAs). They further presented a neuroendocrinological model (Hausmann & Güntürkün, 2000c) that could potentially explain how sex hormones modulate FCAs. Their model proposed that high levels of progesterone reduce the synaptic efficiency of cortico-cortical transmission, leading to a reduction of FCAs. However, empirical data testing their hypothesis directly were missing. Using various approaches, we have now gathered behavioral, electrophysiological, and neuroimaging data that partly support the original idea, while also pointing toward estradiol-modulating FCAs. The current review provides an update on this fascinating topic and briefly explores clinical applications.
Neuropsychologische Genderaspekte bei Patientinnen und Patienten mit Morbus Parkinson
Authors: Ophey Anja , Pauquet Julia , Kalbe Elke
Published: August 2018

Zusammenfassung. Diese Übersichtsarbeit beschäftigt sich mit (neuro-)psychologischen Geschlechtseffekten beim idiopathischen Parkinsonsyndrom (IPS). Frauen mit IPS leiden häufiger an Depressionen als Männer; das Geschlechterverhältnis ist jedoch ausgeglichener als in der Allgemeinbevölkerung. Hinsichtlich der Kognition deuten neue Befunde auf einen stärkeren Abbau des verbalen Gedächtnisses bei Frauen mit IPS hin. Im Bereich Lebensqualität scheinen Geschlechtsunterschiede besonders dann deutlich zu werden, wenn spezifische Unterdomänen der HrQoL betrachtet werden. Zusammenfassend lässt sich feststellen, dass Geschlechtsunterschiede beim IPS in verschiedenen (neuro-)psychologischen Bereichen bestehen und diese klinisch relevant erscheinen. Die Befundlage ist jedoch lückenhaft, und zugrundeliegende Mechanismen sind unklar. Weitere Forschung ist daher erforderlich.
Genderspezifische Leistungsprofile des episodischen Gedächtnisses bei Patientinnen und Patienten mit Alzheimer Demenz
Authors: Pusswald Gisela , Lehrner Johann , Hagmann Michael , Dal-Bianco Peter , Benke Thomas , Loitfelder Marisa , Marksteiner Josef , Mosbacher Jochen , Ransmayr Gerhard , Sanin Gerhard , Schmidt Reinhold , Study Group PRODEM
Published: August 2018

Zusammenfassung. Das Geschlecht wird als wichtiger Einflussfaktor bei der Entwicklung und Progredienz der Alzheimer Demenz gesehen. In dieser Studie wurden geschlechtsspezifische Unterschiede in verschiedenen kognitiven Funktionen bei Patienten mit milder bis moderater Alzheimer Demenz untersucht. Analysiert wurde das kognitive Leistungsprofil mit Hilfe der CERAD-plus Testbatterie von 113 Männern (Alter in Jahren: M = 78, SD = 7.99) und von 173 Frauen (Alter in Jahren: M = 80, SD = 8.63). Wir fanden geschlechtsspezifische Leistungsunterschiede im verbalen Lernen zwischen Männern und Frauen, wobei sich Frauen schlechter als Männer präsentierten. Kontrolliert man für Faktoren wie Depression, Schweregrad und Dauer der Erkrankung, sowie Ausbildungslevel, blieb der geschlechtsspezifische Unterschied erhalten. Dieses Ergebnis weist daraufhin, dass geschlechtsspezifische Unterschiede in der klinischen Untersuchung Beachtung finden sollten.
Recognizing Contributions and Giving Credit
Authors: Hanson Brooks , Webb Susan
Published: August 2018

AGU is working with other leading publishers to implement common standards for authorship and recognize and value specific contributions across cultures.
Combined Influence of the Arctic Oscillation and the Scandinavia Pattern on Spring Surface Air Temperature Variations Over Eurasia
Authors: Chen Shangfeng , Wu Renguang , Song Linye , Chen Wen
Published: August 2018

The present study investigated the joint impacts of the spring Arctic Oscillation (AO) and the Scandinavia (SCAND) teleconnection pattern on spring surface air temperature (SAT) variations over the midhigh latitude Eurasia. It is found that the connection of the spring AO (SCAND) to the first two empirical orthogonal function (EOF) modes of the spring Eurasian SAT variations depends strongly on the phase of the spring SCAND (AO) index. The EOF1 and EOF2 modes display same sign variation and tripole pattern, respectively. In the in‐phase AO‐SCAND years, the mid‐high latitude Eurasia is covered by same sign SAT anomalies, and the spring AO and SCAND indices both have a strong (weak) connection with the EOF1 (EOF2) mode. In the out‐of‐phase AO‐SCAND years, the SAT anomalies over the mid‐high latitude Eurasia are featured by a tripole pattern, and the connection of the spring AO and SCAND indices with the EOF1 (EOF2) is insignificant (significant). Differences in the distribution of SAT anomalies between the in‐phase and out‐of‐phase AO‐SCAND years are attributed to the constructive and destructive superposition of atmospheric circulation anomalies related to the spring AO and SCAND indices. The observed joint impacts of the spring AO and SCAND on spring Eurasian SAT variations are captured by a historical simulation of the flexible global ocean‐atmosphere‐land system model, spectral version 2. Analysis indicates that the prediction skill of the spring Eurasian SAT variations related to the first two EOF modes is enhanced when taking both the spring AO and SCAND signals into account.
Biological determinants of health disparities in multiple myeloma
Authors: Smith Cheryl Jacobs , Ambs Stefan , Landgren Ola
Published: August 2018

Multiple myeloma is a rare plasma cell cancer, and incidence rates among patients of African descent are about twice those among patients of European descent. Rates of multiple myeloma vary among different populations, but the reasons for the racial disparities in multiple myeloma are largely unknown. Epidemiology has identified risk factors for multiple myeloma including race, advanced age, gender, family history, and exposure to different genetic toxins including radiation. Race and ancestry play a large role in predicting the risk for multiple myeloma, yet there exists a paucity of literature that explores the molecular contribution of race and ancestry to disease. In this review, we describe the relevant literature that describes the observed racial differences according to distinct tumor immunobiological and ancestral differences in populations.
BAG3 regulates stability of IL-8 mRNA via interplay between HuR and miR-4312 in PDACs
Authors: Li Chao , Jiang Jing-Yi , Wang Jia-Mei , Sun Jia , An Ming-Xin , Li Si , Yan Jing , Wang Hua-Qin
Published: August 2018

Bcl-2 associated athanogene 3 (BAG3) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), and its high expression appears to be a poor prognostic factor for patients with PDAC. In this study, we show that BAG3 knockdown significantly decreases migration and invasion of PDACs via reduction of interleukine-8 (IL-8) production. BAG3 knockdown regulates IL-8 expression at the posttranscriptional levels via interplay between recruitment of RNA-binding protein HuR and miR-4312. HuR binds to the cis-elements located in the 3′-untranslational region (UTR) of the IL-8 transcript to stabilize it, whereas miR-4312-containing miRNA-induced silencing complex (miRISC) is recruited to the adjacent seed element to destabilize it. The binding of HuR prevents the recruitment of Argonaute (Ago2), overriding miR-4312-mediated translation inhibition of IL-8. BAG3 knockdown decreases cytoplasmic distribution of HuR via increasing its phosphorylation at Ser202, therefore compromising its recruitment while promoting recruitment of miR-4312 containing miRISC to IL-8 transcript. Furthermore, our data indicate that only phosphorylated Ago2 at Ser387 interacts with IL-8 transcript. BAG3 knockdown increases phosphorylation of Ago2 at Ser387, thereby further promoting loading of miR-4312 containing miRISC to IL-8 transcript. Taken together, we propose that BAG3 promotes invasion by stabilizing IL-8 transcript via HuR recruitment, and subsequently suppressing the loading of miR-4312 containing miRISC in PDACs. Our results reveal a novel pathway linking BAG3 expression to enhanced PDAC metastasis, thus making BAG3 a potential target for intervention in pancreatic cancer.
TFEB, a potential therapeutic target for osteoarthritis via autophagy regulation
Authors: Zheng Gang , Zhan Yu , Li Xiaobin , Pan Zongyou , Zheng Fanghong , Zhang Zengjie , Zhou Yifei , Wu Yaosen , Wang Xiangyang , Gao Weiyang , Xu Huazi , Tian Naifeng , Zhang Xiaolei
Published: August 2018

The blockage of autophagic flux in chondrocytes has been considered as a major reason for the excessive cellular apoptosis and senescence in osteoarthritis (OA) development; however, the molecular mechanism and therapeutic strategy for interrupted autophagic flux is still not clear. Most recently, the transcription factor EB (TFEB) is identified as a master regulator for autophagic flux via initiating the expression of multiple autophagy-related genes and lysosomal biogenesis. This research was performed to confirm whether TFEB expression and activity are impacted in OA development and to confirm the effect of genetic up-regulation of TFEB on autophagic flux and cellular protection in the in vitro and in vivo models of OA. We demonstrated that the expression and nuclear localization of TFEB is decreased in human and mouse OA cartilage as well as in tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. Applying lentivirus to transfect chondrocytes, we found that TFEB overexpression rescues the TBHP-induced the autophagic flux damage, lysosome dysfunction and protects chondrocyte against TBHP induced apoptosis and senescence; these protections of TFEB are diminished by chloroquine-medicated autophagy inhibition. Our destabilized medial meniscus (DMM) mouse OA model shows that TFEB overexpression ameliorates the surgery-induced cartilage degradation, restrains the apoptosis and senescence of chondrocyte, and enhances the autophagic flux. In summary, our study indicates that the activity of TFEB in chondrocyte is involved in OA development, also TFEB overexpression may be a promising strategy for OA treatment.
Enhanced autophagy contributes to excitotoxic lesions in a rat model of preterm brain injury
Authors: Descloux Céline , Ginet Vanessa , Rummel Coralie , Truttmann Anita C. , Puyal Julien
Published: August 2018

Cystic periventricular leukomalacia is commonly diagnosed in premature infants, resulting from severe hypoxic-ischemic white matter injury, and also involving some grey matter damage. Very few is known concerning the cell death pathways involved in these types of premature cerebral lesions. Excitotoxicity is a predominant mechanism of hypoxic-ischemic injury in the developing brain. Concomitantly, it has been recently shown that autophagy could be enhanced in excitotoxic conditions switching this physiological intracellular degradation system to a deleterious process. We here investigated the role of autophagy in a validated rodent model of preterm excitotoxic brain damage mimicking in some aspects cystic periventricular leukomalacia. An excitotoxic lesion affecting periventricular white and grey matter was induced by injecting ibotenate, a glutamate analogue, in the subcortical white matter (subcingulum area) of five-day old rat pups. Ibotenate enhanced autophagy in rat brain dying neurons at 24 h as shown by increased presence of autophagosomes (increased LC3-II and LC3-positive dots) and enhanced autophagic degradation (SQSTM1 reduction and increased number and size of lysosomes (LAMP1- and CATHEPSIN B-positive vesicles)). Co-injection of the pharmacological autophagy inhibitor 3-methyladenine prevented not only autophagy induction but also CASPASE-3 activation and calpain-dependent cleavage of SPECTRIN 24 h after the insult, thus providing a strong reduction of the long term brain injury (16 days after ibotenate injection) including lateral ventricle dilatation, decreases in cerebral tissue volume and in subcortical white matter thickness. The autophagy-dependent neuroprotective effect of 3-methyladenine was confirmed in primary cortical neuronal cultures using not only pharmacological but also genetic autophagy inhibition of the ibotenate-induced autophagy. Strategies inhibiting autophagy could then represent a promising neuroprotective approach in the context of severe preterm brain injuries.
ARD1 contributes to IKKβ-mediated breast cancer tumorigenesis
Authors: Zhang Yu , Zhou Hang , Tao Yongjun , Liu Xingyu , Yuan Zhu , Nie Chunlai
Published: August 2018

The expression of IκB kinase β (IKKβ) promotes the growth of breast cancer cells. Meanwhile, IKKβ mediates the phosphorylation and subsequent degradation of arrest-defective protein 1 (ARD1). However, the relationship between IKKβ and ARD1 in the occurrence of breast cancer has not been reported. In this study, we found that IKKβ not only acts directly on mammalian target of rapamycin (mTOR) activity but also indirectly acts on mTOR activity through posttranscriptional modification of ARD1, thereby effectively promoting the growth of breast cancer cells. ARD1 prevents mTOR activity and breast cancer cell growth by stabilizing tuberous sclerosis complex 2 (TSC2) to induce autophagy. Moreover, acetylation of heat shock protein 70 (Hsp70) also contributes to ARD1-mediated autophagy. Therefore, upstream IKKβ can further promote the occurrence of breast cancer by mediating the function of ARD1.
MALAT1–miR663a negative feedback loop in colon cancer cell functions through direct miRNA–lncRNA binding
Authors: Tian Wei , Du Yantao , Ma Yuwan , Gu Liankun , Zhou Jing , Deng Dajun
Published: August 2018

The lncRNA MALAT1 has multiple biological functions, including influencing RNA processing, miRNA sponging, and cancer development. It is acknowledged that miR663a and its targets are inflammation-related genes frequently deregulated in many cancers. The associations between MALAT1 and miR663a and their target genes remain unknown. In this study, it was found that in colon cancer (CC) cells, MALAT1 and miR663a were reciprocally repressed in cDNA array screening and qRT-PCR analysis. However, MALAT1 was significantly upregulated in CC tissues, and miR663a was significantly downregulated relative to the corresponding surgical margin (SM) tissues. An inverse relationship between MALAT1 and miR663a expression was detected among CC tissue samples (n = 172, r = −0.333, p < 0.0001). The RNA-pulldown results showed MALAT1 lncRNA–miR663a binding. The results of luciferase-reporter analysis further revealed that the MALAT1 7038–7059 nt fragment was the miR663a seed sequence. Both miR663a knockdown and MALAT1 activation alone significantly upregulated the expression levels of miR663a targets, including TGFB1, PIK3CD, P53, P21, and JUND, in the CC cell lines HCT116 and SW480. A positive relationship was also observed between the expression levels of MALAT1 and these miR663a targets in the above 172 CC samples and 160 CC samples in publicly available databases. In addition, reciprocal abolishment of the effects of miR663a overexpression and MALAT1 activation on the proliferation, migration, and invasion of cancer cells was also observed, while miR663a upregulation and MALAT1 activation alone inhibited and promoted the behaviors of these CC cell lines, respectively. All these suggested that, as a competing endogenous lncRNA, MALAT1 maybe a dominant protector for the degradation of miR663a targets. miR663a and MALAT1 may consist of a negative feedback loop to determine their roles in CC development.
Crystalline TiO2 protective layer with graded oxygen defects for efficient and stable silicon-based photocathode
Authors: Zheng Jianyun , Lyu Yanhong , Wang Ruilun , Xie Chao , Zhou Huaijuan , Jiang San Ping , Wang Shuangyin
Published: August 2018

The trade-offs between photoelectrode efficiency and stability significantly hinder the practical application of silicon-based photoelectrochemical devices. Here, we report a facile approach to decouple the trade-offs of silicon-based photocathodes by employing crystalline TiO2 with graded oxygen defects as protection layer. The crystalline protection layer provides high-density structure and enhances stability, and at the same time oxygen defects allow the carrier transport with low resistance as required for high efficiency. The silicon-based photocathode with black TiO2 shows a limiting current density of ~35.3 mA cm−2 and durability of over 100 h at 10 mA cm−2 in 1.0 M NaOH electrolyte, while none of photoelectrochemical behavior is observed in crystalline TiO2 protection layer. These findings have significant suggestions for further development of silicon-based, III–V compounds and other photoelectrodes and offer the possibility for achieving highly efficient and durable photoelectrochemical devices.
A terahertz-driven non-equilibrium phase transition in a room temperature atomic vapour
Authors: Wade C. G. , Marcuzzi M. , Levi E. , Kondo J. M. , Lesanovsky I. , Adams C. S. , Weatherill K. J.
Published: August 2018

There are few demonstrated examples of phase transitions that may be driven directly by terahertz frequency electric fields, and those that are known require field strengths exceeding 1 MV cm−1. Here we report a non-equilibrium phase transition driven by a weak (≪1 V cm−1), continuous-wave terahertz electric field. The system consists of room temperature caesium vapour under continuous optical excitation to a high-lying Rydberg state, which is resonantly coupled to a nearby level by the terahertz electric field. We use a simple model to understand the underlying physical behaviour, and we demonstrate two protocols to exploit the phase transition as a narrowband terahertz detector: the first with a fast (20 μs) non-linear response to nano-Watts of incident radiation, and the second with a linearised response and effective noise equivalent power ≤1 pW Hz−1/2. The work opens the door to a class of terahertz devices controlled with low-field intensities and operating in a room temperature environment.
Topographic precision in sensory and motor corticostriatal projections varies across cell type and cortical area
Authors: Hooks Bryan M. , Papale Andrew E. , Paletzki Ronald F. , Feroze Muhammad W. , Eastwood Brian S. , Couey Jonathan J. , Winnubst Johan , Chandrashekar Jayaram , Gerfen Charles R.
Published: August 2018

The striatum shows general topographic organization and regional differences in behavioral functions. How corticostriatal topography differs across cortical areas and cell types to support these distinct functions is unclear. This study contrasted corticostriatal projections from two layer 5 cell types, intratelencephalic (IT-type) and pyramidal tract (PT-type) neurons, using viral vectors expressing fluorescent reporters in Cre-driver mice. Corticostriatal projections from sensory and motor cortex are somatotopic, with a decreasing topographic specificity as injection sites move from sensory to motor and frontal areas. Topographic organization differs between IT-type and PT-type neurons, including injections in the same site, with IT-type neurons having higher topographic stereotypy than PT-type neurons. Furthermore, IT-type projections from interconnected cortical areas have stronger correlations in corticostriatal targeting than PT-type projections do. As predicted by a longstanding model, corticostriatal projections of interconnected cortical areas form parallel circuits in the basal ganglia.
Predicting the evolution of Escherichia coli by a data-driven approach
Authors: Wang Xiaokang , Zorraquino Violeta , Kim Minseung , Tsoukalas Athanasios , Tagkopoulos Ilias
Published: August 2018

A tantalizing question in evolutionary biology is whether evolution can be predicted from past experiences. To address this question, we created a coherent compendium of more than 15,000 mutation events for the bacterium Escherichia coli under 178 distinct environmental settings. Compendium analysis provides a comprehensive view of the explored environments, mutation hotspots and mutation co-occurrence. While the mutations shared across all replicates decrease with the number of replicates, our results argue that the pairwise overlapping ratio remains the same, regardless of the number of replicates. An ensemble of predictors trained on the mutation compendium and tested in forward validation over 35 evolution replicates achieves a 49.2 ± 5.8% (mean ± std) precision and 34.5 ± 5.7% recall in predicting mutation targets. This work demonstrates how integrated datasets can be harnessed to create predictive models of evolution at a gene level and elucidate the effect of evolutionary processes in well-defined environments.
Author Correction: Spatiotemporal regulation of Aurora B recruitment ensures release of cohesion during C. elegans oocyte meiosis
Authors: Ferrandiz Nuria , Barroso Consuelo , Telecan Oana , Shao Nan , Kim Hyun-Min , Testori Sarah , Faull Peter , Cutillas Pedro , Snijders Ambrosius P. , Colaiácovo Monica P. , Martinez-Perez Enrique
Published: August 2018

The original version of this Article contained an error in the spelling of the author Ambrosius P. Snijders, which was incorrectly given as Ambrosious P. Snijders. This has now been corrected in both the PDF and HTML versions of the Article.
Synthesis of chiral α-trifluoromethyl alcohols and ethers via enantioselective Hiyama cross-couplings of bisfunctionalized electrophiles
Authors: Varenikov Andrii , Gandelman Mark
Published: August 2018

Methods for synthesis of chiral organic compounds bearing trifluoromethyl-substituted stereocenters are of great interest for agrochemical and pharmaceutical labs and industries in their search for new bioactive materials. We report on employment of bisfunctionalized electrophiles, bearing both a trifluoromethyl and a functional group as direct substituents of the reactive center, in cross-coupling reactions. We exemplify this concept in the asymmetric synthesis of enantioenriched α-trifluoromethyl- and perfluoroalkyl-containing benzylic and allylic ethers and alcohols by nickel-catalyzed stereoconvergent Hiyama cross-coupling reaction. Substrate electrophiles are conveniently prepared in few steps from trifluoroacetic acid. The method represents a conceptually different approach to chiral CF3-substituted alcohols and ethers and allows for a rapid catalytic preparation of a wide range of these valuable compounds in high yields and enantioselectivity.
Dendrite-targeting interneurons control synaptic NMDA-receptor activation via nonlinear α5-GABAA receptors
Authors: Schulz Jan M. , Knoflach Frederic , Hernandez Maria-Clemencia , Bischofberger Josef
Published: August 2018

Dendrite-targeting GABAergic interneurons powerfully control postsynaptic integration, synaptic plasticity, and learning. However, the mechanisms underlying the efficient GABAergic control of dendritic electrogenesis are not well understood. Using subtype-selective blockers for GABAA receptors, we show that dendrite-targeting somatostatin interneurons and NO-synthase-positive neurogliaform cells preferentially activate α5-subunit- containing GABAA receptors (α5-GABAARs), generating slow inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal cells. By contrast, only negligible contribution of these receptors could be found in perisomatic IPSCs, generated by fast-spiking parvalbumin interneurons. Remarkably, α5-GABAAR-mediated IPSCs were strongly outward-rectifying generating 4-fold larger conductances above –50 mV than at rest. Experiments and modeling show that synaptic activation of these receptors can very effectively control voltage-dependent NMDA-receptor activation as well as Schaffer-collateral evoked burst firing in pyramidal cells. Taken together, nonlinear-rectifying α5-GABAARs with slow kinetics match functional NMDA-receptor properties and thereby mediate powerful control of dendritic postsynaptic integration and action potential firing by dendrite-targeting interneurons.
Dehydrogenative reagent-free annulation of alkenes with diols for the synthesis of saturated O-heterocycles
Authors: Cai Chen-Yan , Xu Hai-Chao
Published: August 2018

Dehydrogenative annulation reactions are among the most straightforward and efficient approach for the preparation of cyclic structures. However, the applications of this strategy for the synthesis of saturated heterocycles have been rare. In addition, reported dehydrogenative bond-forming reactions commonly employ stoichiometric chemical oxidants, the use of which reduces the sustainability of the synthesis and brings safety and environmental issues. Herein, we report an organocatalyzed electrochemical dehydrogenative annulation reaction of alkenes with 1,2- and 1,3-diols for the synthesis of 1,4-dioxane and 1,4-dioxepane derivatives. The combination of electrochemistry and redox catalysis using an organic catalyst allows the electrosynthesis to proceed under transition metal- and oxidizing reagent-free conditions. In addition, the electrolytic method has a broad substrate scope and is compatible with many common functional groups, providing an efficient and straightforward access to functionalized 1,4-dioxane and 1,4-dioxepane products with diverse substitution patterns.
The complex underpinnings of genetic background effects
Authors: Mullis Martin N. , Matsui Takeshi , Schell Rachel , Foree Ryan , Ehrenreich Ian M.
Published: August 2018

Genetic interactions between mutations and standing polymorphisms can cause mutations to show distinct phenotypic effects in different individuals. To characterize the genetic architecture of these so-called background effects, we genotype 1411 wild-type and mutant yeast cross progeny and measure their growth in 10 environments. Using these data, we map 1086 interactions between segregating loci and 7 different gene knockouts. Each knockout exhibits between 73 and 543 interactions, with 89% of all interactions involving higher-order epistasis between a knockout and multiple loci. Identified loci interact with as few as one knockout and as many as all seven knockouts. In mutants, loci interacting with fewer and more knockouts tend to show enhanced and reduced phenotypic effects, respectively. Cross–environment analysis reveals that most interactions between the knockouts and segregating loci also involve the environment. These results illustrate the complicated interactions between mutations, standing polymorphisms, and the environment that cause background effects.
Room-temperature polarized spin-photon interface based on a semiconductor nanodisk-in-nanopillar structure driven by few defects
Authors: Chen Shula , Huang Yuqing , Visser Dennis , Anand Srinivasan , Buyanova Irina A. , Chen Weimin M.
Published: August 2018

Owing to their superior optical properties, semiconductor nanopillars/nanowires in one-dimensional (1D) geometry are building blocks for nano-photonics. They also hold potential for efficient polarized spin-light conversion in future spin nano-photonics. Unfortunately, spin generation in 1D systems so far remains inefficient at room temperature. Here we propose an approach that can significantly enhance the radiative efficiency of the electrons with the desired spin while suppressing that with the unwanted spin, which simultaneously ensures strong spin and light polarization. We demonstrate high optical polarization of 20%, inferring high electron spin polarization up to 60% at room temperature in a 1D system based on a GaNAs nanodisk-in-GaAs nanopillar structure, facilitated by spin-dependent recombination via merely 2–3 defects in each nanodisk. Our approach points to a promising direction for realization of an interface for efficient spin-photon quantum information transfer at room temperature—a key element for future spin-photonic applications.
SCFFBW7-mediated degradation of Brg1 suppresses gastric cancer metastasis
Authors: Huang Li-Yu , Zhao Junjie , Chen Hao , Wan Lixin , Inuzuka Hiroyuki , Guo Jianping , Fu Xuhong , Zhai Yangyang , Lu Zhaoning , Wang Xuefei , Han Ze-Guang , Sun Yihong , Wei Wenyi
Published: August 2018

Brg1/SMARCA4 serves as the ATPase and the helicase catalytic subunit for the multi-component SWI/SNF chromatin remodeling complex, which plays a pivotal role in governing chromatin structure and gene transcription. However, the upstream signaling pathways regulating Brg1 protein stability and its physiological contribution to carcinogenesis remain largely elusive. Here we report that Brg1 is a bona fide ubiquitin substrate of SCFFBW7. We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation. In keeping with a tumor suppressive role of FBW7 in human gastric cancer, we find an inverse correlation between FBW7 and Brg1 expression in human gastric cancer clinical samples. Mechanistically, we find that stabilization of Brg1 in gastric cancer cells suppresses E-cadherin expression, subsequently promoting gastric cancer metastasis. Hence, this previously unknown FBW7/Brg1 signaling axis provides the molecular basis and the rationale to target Brg1 in FBW7-compromised human gastric cancers.
Carboxysome encapsulation of the CO2-fixing enzyme Rubisco in tobacco chloroplasts
Authors: Long Benedict M. , Hee Wei Yih , Sharwood Robert E. , Rae Benjamin D. , Kaines Sarah , Lim Yi-Leen , Nguyen Nghiem D. , Massey Baxter , Bala Soumi , von Caemmerer Susanne , Badger Murray R. , Price G. Dean
Published: August 2018

A long-term strategy to enhance global crop photosynthesis and yield involves the introduction of cyanobacterial CO2-concentrating mechanisms (CCMs) into plant chloroplasts. Cyanobacterial CCMs enable relatively rapid CO2 fixation by elevating intracellular inorganic carbon as bicarbonate, then concentrating it as CO2 around the enzyme Rubisco in specialized protein micro-compartments called carboxysomes. To date, chloroplastic expression of carboxysomes has been elusive, requiring coordinated expression of almost a dozen proteins. Here we successfully produce simplified carboxysomes, isometric with those of the source organism Cyanobium, within tobacco chloroplasts. We replace the endogenous Rubisco large subunit gene with cyanobacterial Form-1A Rubisco large and small subunit genes, along with genes for two key α-carboxysome structural proteins. This minimal gene set produces carboxysomes, which encapsulate the introduced Rubisco and enable autotrophic growth at elevated CO2. This result demonstrates the formation of α-carboxysomes from a reduced gene set, informing the step-wise construction of fully functional α-carboxysomes in chloroplasts.