FMRP regulates presynaptic localization of neuronal voltage gated calcium channels

Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism, results from the loss of fragile X mental retardation protein (FMRP). We have recently identified a direct interaction of FMRP with voltage-gated Ca2+ channels that modulates neurotransmitter release. In the present study we used a combination of optophysiological tools to investigate the impact of FMRP on the targeting of voltage-gated Ca2+ channels to the active zones in neuronal presynaptic terminals. We monitored Ca2+ transients at synaptic boutons of dorsal root ganglion (DRG) neurons using the genetically-encoded Ca2+ indicator GCaMP6f tagged to synaptophysin. We show that knock-down of FMRP induces an increase of the amplitude of the Ca2+ transient in functionally-releasing presynaptic terminals, and that this effect is due to an increase of N-type Ca2+ channel contribution to the total Ca2+ transient. Dynamic regulation of CaV2.2 channel trafficking is key to the function of these channels in neurons. Using a CaV2.2 construct with an α-bungarotoxin binding site tag, we further investigate the impact of FMRP on the trafficking of CaV2.2 channels. We show that forward trafficking of CaV2.2 channels from the endoplasmic reticulum to the plasma membrane is reduced when co-expressed with FMRP. Altogether our data reveal a critical role of FMRP on localization of CaV channels to the presynaptic terminals and how its defect in a context of FXS can profoundly affect synaptic transmission

Adherence to Mediterranean Diet Pattern among Spanish Adults Attending a Medical Centre: Nondiabetic Subjects and Type 1 and 2 Diabetic Patients.

Objective. To identify adherence to Mediterranean diet among two groups of Spanish adults: diabetic patients and nondiabetic subjects. Methods. Adherence to Mediterranean diet was measured by a 14-item screener (scale: 0–14; =5: low, 6–9: moderate, and =10: high) in 351 volunteers. Results. Mean age was 50.97±12.58 in nondiabetics (n=154) and 59.50±13.34 in diabetics (n = 197). The whole sample scored 8.77 ± 1.82. Score was 9.19 ± 1.84 in nondiabetic females (n = 58) and 8.15 ± 1.79 in diabetic females (n = 85) (p = 0 003), due to lower consumption of olive oil (p = 0 005) and nuts (p = 0 000). Type 2 diabetic males (n = 79; 8.76 ± 1.88) consumed less olive oil than healthy males (n = 28; 9.36 ± 1.59) (p = 0 046). Up to 30-year-old nondiabetics scored lower than more than 60-year-old nondiabetics (8.40 ± 1.5 versus 9.74 ± 2.03; p = 0 047). The youngest ate less olive oil (p = 0 002) and more pastries (p = 0 007). Conclusions. The sample presented moderate adherence to Mediterranean diet in all subgroups. Scientific evidence about the benefits of Mediterranean diet, olive oil, and nuts supports the recommendation to increase consumption of olive oil and nuts in diabetic women and of daily olive oil in type 2 diabetic men, reducing consumption of red meat, butter, and pastries, and to promote Mediterranean diet among the youngest of the sample studie

Separable time-causal and time-recursive spatio-temporal receptive fields

We present an improved model and theory for time-causal and time-recursive spatio-temporal receptive fields, obtained by a combination of Gaussian receptive fields over the spatial domain and first-order integrators or equivalently truncated exponential filters coupled in cascade over the temporal domain. Compared to previous spatio-temporal scale-space formulations in terms of non-enhancement of local extrema or scale invariance, these receptive fields are based on different scale-space axiomatics over time by ensuring non-creation of new local extrema or zero-crossings with increasing temporal scale. Specifically, extensions are presented about parameterizing the intermediate temporal scale levels, analysing the resulting temporal dynamics and transferring the theory to a discrete implementation in terms of recursive filters over time.Comment: 12 pages, 2 figures, 2 tables. arXiv admin note: substantial text overlap with arXiv:1404.203

Preparation of Ni–YSZ thin and thick films on metallic interconnects as cell supports. Applications as anode for SOFC

In this work, we propose the preparation of a duplex anodic layer composed of both a thin (100 nm) and a thick film (10 lm) with Ni–YSZ material. The support of this anode is a metallic substrate, which is the interconnect of the SOFC unit cell. The metallic support limits the temperature of thermal treatment at 800 C to keep a good interconnect mechanical behaviour and to reduce corrosion. We have chosen to elaborate anodic coatings by sol–gel route coupled with dip-coating process, which are low cost techniques and allow working with moderate temperatures. Thin films are obtained by dipping interconnect substrate into a sol, and thick films into an optimized slurry. After thermal treatment at only 800 C, anodic coatings are adherent and homogeneous. Thin films have compact microstructures that confer ceramic protective barrier on metal surface. Further coatings of 10 lm thick are porous and constitute the active anodic material

Soft tissues, areal bone mineral density and hip geometry estimates in active young boys: The PRO-BONE study

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Purpose: Soft tissues, such as fat mass (FM) and lean mass (LM), play an important role in bone development but this is poorly understood in highly active youths. The objective of this study was to determine whether FM or LM is a stronger predictor of areal bone mineral density (aBMD) and hip geometry estimates in a group of physically active boys after adjusting for height, chronological age, moderate-to-vigorous physical activity (MVPA), FM, and LM. Methods: Participants included 121 boys (13.1±1.0 years) from the PRO-BONE study. Bone mineral content (BMC) and aBMD measured at total body, femoral neck and lumbar spine using dual-energy X-ray absorptiometry (DXA), and hip structural analysis was used to estimate bone geometry at the femoral neck. Body composition was assessed using DXA. The relationships of FM and LM with bone outcomes were analysed using simple and multiple linear regression analyses. Results: Pearson correlation coefficients showed that total body (less head) aBMD was significantly correlated with LM but not FM. Multiple linear regression analyses showed that FM, after accounting for height, age, MVPA and LM had no significant relationship with aBMD or hip geometry estimates, except for arms aBMD. By contrast, there were positive associations between LM and most aBMD and hip geometry estimates, after accounting height, age, MVPA and FM. Conclusions: The results of this study suggest that LM, and not FM, is the stronger predictor of aBMD and hip geometry estimates in physically active boys.The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007–2013] under grant agreement no. PCIG13-GA-2013-618496

Network segregation in a model of misinformation and fact checking

Misinformation under the form of rumor, hoaxes, and conspiracy theories spreads on social media at alarming rates. One hypothesis is that, since social media are shaped by homophily, belief in misinformation may be more likely to thrive on those social circles that are segregated from the rest of the network. One possible antidote is fact checking which, in some cases, is known to stop rumors from spreading further. However, fact checking may also backfire and reinforce the belief in a hoax. Here we take into account the combination of network segregation, finite memory and attention, and fact-checking efforts. We consider a compartmental model of two interacting epidemic processes over a network that is segregated between gullible and skeptic users. Extensive simulation and mean-field analysis show that a more segregated network facilitates the spread of a hoax only at low forgetting rates, but has no effect when agents forget at faster rates. This finding may inform the development of mitigation techniques and overall inform on the risks of uncontrolled misinformation online

Regulation of the Respiration Quotient Across Ocean Basins

A key uncertainty for predicting future ocean oxygen levels is the response and feedback of organic matter respiration demand. One poorly constrained component of the respiration demand is the oxygen-to-carbon remineralization ratio—the respiration quotient. Currently, multiple biological hypotheses can explain variation in the respiration quotient of organic matter produced in the surface ocean. To test these hypotheses, we directly quantified the particulate respiration quotient in 715 samples along a meridional section of the Atlantic Ocean and compared to previous Pacific Ocean observations. We demonstrate significant regional shifts in the respiration quotient and a two-basin average of 1.16. Possible diel oscillations were also observed in the respiration quotient. Basin and regional variation in the respiration quotient were positively linked to temperature, N versus P stress, and plankton size structure. These observations suggest a complex regulation of the respiration quotient with important implications for the regional coupling of carbon and oxygen cycling

CDH1 mutation distribution and type suggests genetic differences between the etiology of orofacial clefting and gastric cancer

Pathogenic variants in CDH1, encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available CDH1 variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least ‘likely pathogenic’, and correlates their molecular and structural characteristics to phenotype. We demonstrate that CDH1 variant type and location differ between HDGC and CL/P, and that there is clustering of CL/P variants within linker regions between the extracellular domains of the cadherin protein. While these differences do not provide for exact prediction of the phenotype for a given mutation, they may contribute to more accurate assessments of risk for HDGC or CL/P for individuals with specific CDH1 variants

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis

Podoplanin drives dedifferentiation and amoeboid invasion of melanoma

Melanoma is an aggressive skin cancer developing from melanocytes, frequently resulting in metastatic disease. Melanoma cells utilize amoeboid migration as mode of local invasion. Amoeboid invasion is characterized by rounded cell morphology and high actomyosin contractility driven by Rho GTPase signalling. Migrastatic drugs targeting actin polymerization and contractility are therefore a promising treatment option for metastatic melanoma. To predict amoeboid invasion and metastatic potential, biomarkers functionally linked to contractility pathways are needed. The glycoprotein podoplanin drives actomyosin contractility in lymphoid fibroblasts and is overexpressed in many cancers. We show that podoplanin enhances amoeboid invasion in melanoma. Podoplanin expression in murine melanoma drives rounded cell morphology, increasing motility, and invasion in vivo. Podoplanin expression is increased in a subset of dedifferentiated human melanoma, and in vitro is sufficient to upregulate melanoma-associated marker Pou3f2/Brn2. Together, our data define podoplanin as a functional biomarker for dedifferentiated invasive melanoma and a promising migrastatic therapeutic target