A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons

Analysis of Response of Flexible Pavements Using Finite Element Method

The characteristic response of flexible pavements under traffic load depict a delayed lateral strain relaxation (Viscoelasticity), a phenomenon that may be more accurately and expeditiously analysed using finite element (FE) viscoelastic response models. In this study a flexible pavement was modelled using ANSYS/ED finite element software suite. The pavement model was subjected to cyclic loading that simulated three levels of truck loads on 10R20 tyres at four tyre inflation pressures (viz. 350,490,630 and 770 kPa). The modelled results were in good agreement with the measured in-situ full-scale test data. Therefore, for known pavement material characteristics and tyre-pavement contact regime, finite element method could be used to efficiently estimate the fatigue life of flexible pavement with thin bituminous surfacing layers

Chromatin status and transcription factor binding to gonadotropin promoters in gonadotrope cell lines.

BackgroundProper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for pubertal onset and reproduction. To further our understanding of the molecular events taking place during embryonic development, leading to expression of the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we characterized chromatin structure changes, imparted mainly by histone modifications, in model gonadotrope cell lines.MethodsWe evaluated chromatin status and gene expression profiles by chromatin immunoprecipitation assays, DNase sensitivity assay, and RNA sequencing in three developmentally staged gonadotrope cell lines, αT1-1 (progenitor, expressing Cga), αT3-1 (immature, expressing Cga and Gnrhr), and LβT2 (mature, expressing Cga, Gnrhr, Lhb, and Fshb), to assess changes in chromatin status and transcription factor access of gonadotrope-specific genes.ResultsWe found the common mRNA α-subunit of LH and FSH, called Cga, to have an open chromatin conformation in all three cell lines. In contrast, chromatin status of Gnrhr is open only in αT3-1 and LβT2 cells. Lhb begins to open in LβT2 cells and was further opened by activin treatment. Histone H3 modifications associated with active chromatin were high on Gnrhr in αT3-1 and LβT2, and Lhb in LβT2 cells, while H3 modifications associated with repressed chromatin were low on Gnrhr, Lhb, and Fshb in LβT2 cells. Finally, chromatin status correlates with the progressive access of LHX3 to Cga and Gnrhr, followed by PITX1 binding to the Lhb promoter.ConclusionOur data show the gonadotrope-specific genes Cga, Gnrhr, Lhb, and Fshb are not only controlled by developmental transcription factors, but also by epigenetic mechanisms that include the modulation of chromatin structure, and histone modifications

Motivational factors influencing farming practices in northern Ghana

Socio-economic factors that influence the adoption of management practices and technologies by farmers have received wide attention in the adoption literature, but the effects of socio-psychological farmer features such as perceptions and motivations have been analysed to a lesser extent. Using farm household survey data from three regions in northern Ghana, this study explores farmers’ motivations and perceived adoption impediments for three sustainable intensification practices (SIPs): improved maize varieties, cropping system strategies, and combined SIPs (i.e. improved maize and cropping system strategies), and the effect of motivational factors on decisions to adopt SIPs. First, explorative factor analysis (EFA) was used in identifying factors of motivations and impediments for adoption of SIPs. Then, a multinomial logit model was used to analyze the effect of socio-economic farm characteristics and motivational factors on farmers’ decisions to adopt SIPs. EFA identified three motivational factors: personal satisfaction, eco-diversity and eco-efficiency, which differed in importance between the three regions. Across these regions, higher scores for aspects of personal satisfaction were associated with lower interest in improved maize varieties compared to cropping system strategies, while the opposite was true for eco-efficiency which was related to a stronger preference for improved maize varieties. Uncertainty, absence of social support, and resource constraints were identified as impediment factors. The logit model demonstrated that extension services seemed to support the use of improved maize varieties more than the implementation of cropping system strategies. We conclude that motivational factors significantly influence farmer adoption decisions regarding sustainable intensification practices and should be considered systematically in combination with socio-economic farm features and external drivers to inform on-farm innovation processes and supporting policies.</p

Mechanical Ventilator for Delivery of 17O2 in Brief Pulses

The 17O nucleus has been used recently by several groups for magnetic resonance (MR) imaging of cerebral metabolism. Inhalational delivery of 17O2 in very brief pulses could, in theory, have significant advantages for determination of the cerebral metabolic rate for oxygen (CMRO2) with MR imaging. Mechanical ventilators, however, are not typically capable of creating step changes in gas concentration at the airway. We designed a ventilator for large animal and human studies that provides mechanical ventilation to a subject inside an MR scanner through 25 feet of small-bore connecting tubing, and tested its capabilities using helium as a surrogate for 17O2. After switching the source gas from oxygen to helium, the 0-90% response time for helium concentration changes at the airway was 2.4 seconds. The capability for creating rapid step changes in gas concentration at the airway in large animal and human studies should facilitate the experimental testing of the delivery 17O2 in brief pulses, and its potential use in imaging CMRO2

Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo

Purpose: External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. Materials and methods: We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. Results: IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p = 0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p = 0.04). Conclusions: Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial.Peer-reviewedPublisher Version1721

A Keplerian Circumbinary Disk around the Protobinary System L1551 NE

We present SubMillimeter-Array observations of a Keplerian disk around the Class I protobinary system L1551 NE in 335 GHz continuum emission and submillimeter line emission in 13CO (J=3-2) and C18O (J=3-2) at a resolution of ~120 x 80 AU. The 335-GHz dust-continuum image shows a strong central peak closely coincident with the binary protostars and likely corresponding to circumstellar disks, surrounded by a ~600 x 300 AU feature elongated approximately perpendicular to the [Fe II] jet from the southern protostellar component suggestive of a circumbinary disk. The 13CO and C18O images confirm that the circumbinary continuum feature is indeed a rotating disk; furthermore, the C18O channel maps can be well modeled by a geometrically-thin disk exhibiting Keplerian rotation. We estimate a mass for the circumbinary disk of ~0.03-0.12 Msun, compared with an enclosed mass of ~0.8 Msun that is dominated by the protobinary system. Compared with several other Class I protostars known to exhibit Keplerian disks, L1551 NE has the lowest bolometric temperature (~91 K), highest envelope mass (~0.39 Msun), and the lowest ratio in stellar mass to envelope + disk + stellar mass (~0.65). L1551 NE may therefore be the youngest protostellar object so far found to exhibit a Keplerian disk. Our observations present firm evidence that Keplerian disks around binary protostellar systems, ``Keplerian circumbinary disks', can exist. We speculate that tidal effects from binary companions could transport angular momenta toward the inner edge of the circumbinary disk and create the Keplerian circumbinary disk.Comment: 27 pages, 8 figure

Notices sur les collaborateurs et les collaboratrices

Periprosthetic fracture (PF) after primary total hip replacement (THR) is an uncommon but potentially devastating complication. We analysed data on 257,202 primary THRs with cemented stems and 390 linked first revisions for PF recorded in the National Joint Registry (NJR) of England and Wales to determine if cemented femoral stem brand was associated with the risk of having revision for a PF after primary THR. All cemented femoral stem brands with more than 10,000 primary operations recorded in the NJR were identified. The four most commonly used cemented femoral stems were: Exeter V40 (n=146,409), CPT (n=24,300), C-Stem (n=15,113) and Charnley (n=20,182). We compared the revision risk ratios due to PF amongst the stems using a Poisson regression model adjusting for patient factors. Compared to the Exeter V40, the age, gender and ASA grade adjusted revision rate ratio for the cemented CPT stem was 3.89 (95%CI 3.07,4.93), for the C-Stem 0.89 (95%CI 0.57,1.41) and for the Charnley stem 0.41 (95%CI 0.24,0.70). Limitations of the study include incomplete data capture, analysis of only PF requiring revision and that observation does not imply causality. Nevertheless, this study demonstrates that the choice of a cemented stem is associated with the risk of revision for PF. </p

Constraining the period of the ringed secondary companion to the young star J1407 with photographic plates

Context. The 16 Myr old star 1SWASP J140747.93-394542.6 (V1400 Cen) underwent a series of complex eclipses in May 2007, interpreted as the transit of a giant Hill sphere filling debris ring system around a secondary companion, J1407b. No other eclipses have since been detected, although other measurements have constrained but not uniquely determined the orbital period of J1407b. Finding another eclipse towards J1407 will help determine the orbital period of the system, the geometry of the proposed ring system and enable planning of further observations to characterize the material within these putative rings. Aims. We carry out a search for other eclipses in photometric data of J1407 with the aim of constraining the orbital period of J1407b. Methods. We present photometry from archival photographic plates from the Harvard DASCH survey, and Bamberg and Sonneberg Observatories, in order to place additional constraints on the orbital period of J1407b by searching for other dimming and eclipse events. Using a visual inspection of all 387 plates and a period-folding algorithm we performed a search for other eclipses in these data sets. Results. We find no other deep eclipses in the data spanning from 1890 to 1990, nor in recent time-series photometry from 2012-2018. Conclusions. We rule out a large fraction of putative orbital periods for J1407b from 5 to 20 years. These limits are still marginally consistent with a large Hill sphere filling ring system surrounding a brown dwarf companion in a bound elliptical orbit about J1407. Issues with the stability of any rings combined with the lack of detection of another eclipse, suggests that J1407b may not be bound to J1407.Comment: 8 pages, 3 tables, 4 figures, accepted for publication in A&A. LaTeX files of the paper, scripts for the figures, and a minimal working FPA can be found under https://github.com/robinmentel/Constraining-Period