bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer’s Disease
Authors: Lancaster Melissa A. , Seidenberg Michael , Smith J. Carson , Nielson Kristy A. , Woodard John L. , Durgerian Sally , Rao Stephen M.
Published: December 2016

Objectives:White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer’s disease (AD).Methods:Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1–5, immediate recall, and delayed recall scores and baseline DTI measures; MTL gray matter (GM) and WM volumes; demographics; and AD genetic and metabolic risk factors.Results:Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, FH, and metabolic risk factors did not. Both ε4 status and DTI correlated with change in immediate recall.Conclusions:Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD. (JINS, 2016,22, 1005–1015)
Well-formed lists: specificational copular sentences as predicative inversion constructions
Authors: PATTEN AMANDA L.
Published: December 2016

This article re-examines the case for analysing specificational NP be NP sentences as predicative inversions. Taking a constructional and functional perspective, I show that only predicational sentences exhibiting a relation of class inclusion permit a specificational interpretation, and argue, following Higgins (1979), that the form of specificational inversion sentences is dependent upon the construction-specific concept of specificational meaning. In this way, the account provides an explanation for the restrictions on NP predicative inversion that have posed a problem for inverse analyses developed from within the formalist tradition. Since the distributional facts can be better captured than with the alternative equative approach (which treats specificational sentences as instances of semantic equation), the article concludes that specificational copular sentences are best analysed as instances of predicative inversion.
‘Pesky gNATs’: investigating the feasibility of a novel computerized CBT intervention for adolescents with anxiety and/or depression in a Tier 3 CAMHS setting
Authors: Chapman Rosanna , Loades Maria , O'Reilly Gary , Coyle David , Patterson Mags , Salkovskis Paul
Published: December 2016

Increasingly, evidence suggests that computerized Cognitive Behavioural Therapy (cCBT) is effective at reducing adolescent anxiety and depression for young people in the general population or those ‘at risk’. However, less is known about the acceptability, feasibility and effectiveness of cCBT for adolescents with clinically significant levels of impairment. This study aimed to investigate the feasibility of using a novel cCBT intervention, ‘Pesky gNATs’, with adolescents aged between 13–18 years with anxiety and/or depression who met the criteria for specialist mental health services. Eleven participants were recruited from a Tier 3 child and adolescent mental health service (CAMHS). Recruitment, attendance and retention rates were recorded and qualitative feedback about the benefits and disadvantages of completing cCBT were obtained during the final session. In addition, a number of outcome measures were completed pre- and post- intervention to assess reliable and clinically significant change. The intervention was very brief comprising of just seven sessions. Participants showed high recruitment and retention rates. All participants who started the intervention completed it. All described the programme as useful and the majority identified several benefits. Four of 11 participants demonstrated reliable reductions in symptoms of depression and anxiety and six of 11 showed decreases in parent-reported symptoms of anxiety and depression following the seven-session intervention. This study demonstrates the acceptability and feasibility of using cCBT in a Tier 3 CAMHS setting. Further research is required to investigate the effect of Pesky gNATs on anxiety and depression in other Tier 3 settings.
From Science to Storytelling: An Experiment in Journalism
Authors: Sidder Aaron
Published: December 2016

From ominous deadlines to Internet trolls, AGU's 2016 AAAS Mass Media Fellow recounts his experience writing for National Geographic as a science journalist.
Large-scale pharmacological profiling of 3D tumor models of cancer cells
Authors: Mathews Griner Lesley A , Zhang Xiaohu , Guha Rajarshi , McKnight Crystal , Goldlust Ian S , Lal-Nag Madhu , Wilson Kelli , Michael Sam , Titus Steve , Shinn Paul , Thomas Craig J , Ferrer Marc
Published: December 2016

The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery. To date, small-scale screens have demonstrated that pharmacological responses tend to differ between 2D and 3D cancer cell growth models. However, the limited scope of screens using 3D models has not provided a clear delineation of the cellular pathways and processes that differentially regulate cell survival and death in the different in vitro tumor models. Here we sought to further understand the differences in pharmacological responses between cancer tumor cells grown in different conditions by profiling a large collection of 1912 chemotherapeutic agents. We compared pharmacological responses obtained from cells cultured in traditional 2D monolayer conditions with those responses obtained from cells forming spheres versus cells already in 3D spheres. The target annotation of the compound library screened enabled the identification of those key cellular pathways and processes that when modulated by drugs induced cell death in all growth conditions or selectively in the different cell growth models. In addition, we also show that many of the compounds targeting these key cellular functions can be combined to produce synergistic cytotoxic effects, which in many cases differ in the magnitude of their synergism depending on the cellular model and cell type. The results from this work provide a high-throughput screening framework to profile the responses of drugs both as single agents and in pairwise combinations in 3D sphere models of cancer cells.
miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer
Authors: Wang Xiao , Liang Zhen , Xu Xin , Li Jiangfeng , Zhu Yi , Meng Shuai , Li Shiqi , Wang Song , Xie Bo , Ji Alin , Liu Ben , Zheng Xiangyi , Xie Liping
Published: December 2016

miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells. miR-148a-3p inhibits bladder cancer cell proliferation and epithelial–mesenchymal transition (EMT) by regulating ERBB3/AKT2/c-myc and ERBB3/AKT2/Snail signaling. ERBB3, DNMT1 and AKT2 are downstream miR-148a-3p target genes. Furthermore, the miR-148a-3p/ERBB3/AKT2/c-myc signaling axis establishes a positive feedback loop in the regulation of bladder cancer. Taken together, our study demonstrates novel regulatory circuits involving miR-148a-3p/ERBB3/AKT2/c-myc and DNMT1 that controls bladder cancer progression, which may be useful in the development of more effective therapies against bladder cancer.
1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis
Authors: Wei Chunyan , Mei Jie , Tang Lingli , Liu Yukai , Li Dajin , Li Mingqing , Zhu Xiaoyong
Published: December 2016

Foxp3+ regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of Treg cells, mainly IL-10+ Treg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated Treg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of Treg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for Treg differentiation in the ectopic lesion, especially that for CD4high Treg. Therefore, MRC2-silenced ESCs-educated Treg manifested a stronger suppressive function in vitro. Consistently, the percentage of Treg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of Treg and is involved in the development of endometriosis. Thus, blockage of IDO1 in the ectopic lesion, which does not influence physiological functions of estrogen, may be considered a potential therapy for endometriosis.
Therapeutic advantage of pro-electrophilic drugs to activate the Nrf2/ARE pathway in Alzheimer’s disease models
Authors: Lipton Stuart A , Rezaie Tayebeh , Nutter Anthony , Lopez Kevin M , Parker James , Kosaka Kunio , Satoh Takumi , McKercher Scott R , Masliah Eliezer , Nakanishi Nobuki
Published: December 2016

Alzheimer’s disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ. For in vivo studies, we used two transgenic mouse models of AD, human amyloid precursor protein (hAPP)-J20 mice and triple transgenic (3xTg AD) mice. We treated these mice trans-nasally with CA twice weekly for 3 months. Subsequently, we performed neurobehavioral tests and quantitative immunohistochemistry to assess effects on AD-related phenotypes, including learning and memory, and synaptic damage. In vitro, CA reduced dendritic spine loss in rat neurons exposed to oligomeric Aβ. In vivo, CA treatment of hAPP-J20 mice improved learning and memory in the Morris water maze test. Histologically, CA increased dendritic and synaptic markers, and decreased astrogliosis, Aβ plaque number, and phospho-tau staining in the hippocampus. We conclude that CA exhibits therapeutic benefits in rodent AD models and since the FDA has placed CA on the ‘generally regarded as safe’ (GRAS) list, thus obviating the need for safety studies, human clinical trials will be greatly expedited.
Alternative splicing of a cryptic exon embedded in intron 6 of SMN1 and SMN2
Authors: Yoshimoto Satomi , Harahap Nur Imma Fatimah , Hamamura Yuko , Ar Rochmah Mawaddah , Shima Ai , Morisada Naoya , Shinohara Masakazu , Saito Toshio , Saito Kayoko , Lai Poh San , Matsuo Masafumi , Awano Hiroyuki , Morioka Ichiro , Iijima Kazumoto , Nishio Hisahide
Published: December 2016

Both survival of motor neuron (SMN) genes are associated with spinal muscular atrophy; mutations in SMN1 cause the disease, and SMN2 modulates its severity. It is established that different alternative splicing of exon 7 occurs for SMN1 and SMN2, and a cryptic exon was recently found in intron 6 of both genes. Here, we characterize this cryptic exon and clarify its alternative splicing pattern in control and spinal muscular atrophy cells.
Nitrous oxide as a function of oxygen and archaeal gene abundance in the North Pacific
Authors: Trimmer Mark , Chronopoulou Panagiota-Myrsini , Maanoja Susanna T. , Upstill-Goddard Robert C. , Kitidis Vassilis , Purdy Kevin J.
Published: December 2016

Oceanic oxygen minimum zones are strong sources of the potent greenhouse gas N2O but its microbial source is unclear. We characterized an exponential response in N2O production to decreasing oxygen between 1 and 30 μmol O2 l−1 within and below the oxycline using 15NO2−, a relationship that held along a 550 km offshore transect in the North Pacific. Differences in the overall magnitude of N2O production were accounted for by archaeal functional gene abundance. A one-dimensional (1D) model, parameterized with our experimentally derived exponential terms, accurately reproduces N2O profiles in the top 350 m of water column and, together with a strong 45N2O signature indicated neither canonical nor nitrifier–denitrification production while statistical modelling supported production by archaea, possibly via hybrid N2O formation. Further, with just archaeal N2O production, we could balance high-resolution estimates of sea-to-air N2O exchange. Hence, a significant source of N2O, previously described as leakage from bacterial ammonium oxidation, is better described by low-oxygen archaeal production at the oxygen minimum zone’s margins.
LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells
Authors: Zhu Pingping , Wang Yanying , Wu Jiayi , Huang Guanling , Liu Benyu , Ye Buqing , Du Ying , Gao Guangxia , Tian Yong , He Lei , Fan Zusen
Published: December 2016

Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC). However, the biology of hepatic CSCs remains largely undefined. Through analysis of transcriptome microarray data, we identify a long noncoding RNA (lncRNA) called lncBRM, which is highly expressed in liver CSCs and HCC tumours. LncBRM is required for the self-renewal maintenance of liver CSCs and tumour initiation. In liver CSCs, lncBRM associates with BRM to initiate the BRG1/BRM switch and the BRG1-embedded BAF complex triggers activation of YAP1 signalling. Moreover, expression levels of lncBRM together with YAP1 signalling targets are positively correlated with tumour severity of HCC patients. Therefore, lncBRM and YAP1 signalling may serve as biomarkers for diagnosis and potential drug targets for HCC.
Chirped pulse amplification in an extreme-ultraviolet free-electron laser
Authors: Gauthier David , Allaria Enrico , Coreno Marcello , Cudin Ivan , Dacasa Hugo , Danailov Miltcho Boyanov , Demidovich Alexander , Di Mitri Simone , Diviacco Bruno , Ferrari Eugenio , Finetti Paola , Frassetto Fabio , Garzella David , Künzel Swen , Leroux Vincent , Mahieu Benoît , Mahne Nicola , Meyer Michael , Mazza Tommaso , Miotti Paolo , Penco Giuseppe , Raimondi Lorenzo , Ribič Primož Rebernik , Richter Robert , Roussel Eléonore , Schulz Sebastian , Sturari Luca , Svetina Cristian , Trovò Mauro , Walker Paul Andreas , Zangrando Marco , Callegari Carlo , Fajardo Marta , Poletto Luca , Zeitoun Philippe , Giannessi Luca , De Ninno Giovanni
Published: December 2016

Chirped pulse amplification in optical lasers is a revolutionary technique, which allows the generation of extremely powerful femtosecond pulses in the infrared and visible spectral ranges. Such pulses are nowadays an indispensable tool for a myriad of applications, both in fundamental and applied research. In recent years, a strong need emerged for light sources producing ultra-short and intense laser-like X-ray pulses, to be used for experiments in a variety of disciplines, ranging from physics and chemistry to biology and material sciences. This demand was satisfied by the advent of short-wavelength free-electron lasers. However, for any given free-electron laser setup, a limit presently exists in the generation of ultra-short pulses carrying substantial energy. Here we present the experimental implementation of chirped pulse amplification on a seeded free-electron laser in the extreme-ultraviolet, paving the way to the generation of fully coherent sub-femtosecond gigawatt pulses in the water window (2.3–4.4 nm).
In silico Mapping of Protein Unfolding Mutations for Inherited Disease
Authors: McCafferty Caitlyn L. , Sergeev Yuri V.
Published: December 2016

The effect of disease-causing missense mutations on protein folding is difficult to evaluate. To understand this relationship, we developed the unfolding mutation screen (UMS) for in silico evaluation of the severity of genetic perturbations at the atomic level of protein structure. The program takes into account the protein-unfolding curve and generates propensities using calculated free energy changes for every possible missense mutation at once. These results are presented in a series of unfolding heat maps and a colored protein 3D structure to show the residues critical to the protein folding and are available for quick reference. UMS was tested with 16 crystal structures to evaluate the unfolding for 1391 mutations from the ProTherm database. Our results showed that the computational accuracy of the unfolding calculations was similar to the accuracy of previously published free energy changes but provided a better scale. Our residue identity control helps to improve protein homology models. The unfolding predictions for proteins involved in age-related macular degeneration, retinitis pigmentosa, and Leber’s congenital amaurosis matched well with data from previous studies. These results suggest that UMS could be a useful tool in the analysis of genotype-to-phenotype associations and next-generation sequencing data for inherited diseases.
A previously unreported impact of a PLA2G7 gene polymorphism on the plasma levels of lipoprotein-associated phospholipase A2 activity and mass
Authors: Qi Yue , Zhao Dong , Jia Zhangrong , Wang Wei , Wang Miao , Sun Jiayi , Liu Jun , Li Yan , Xie Wuxiang , Liu Jing
Published: December 2016

Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with the development of atherosclerosis. We aimed to assess the genetic determinants of Lp-PLA2 activity and mass by genotyping multiple polymorphisms in PLA2G7, the gene encoding Lp-PLA2, among 1258 participants from the Chinese Multi-provincial Cohort Study-Beijing Project. The Sequenom MassARRAY system, Taqman assay and direct sequencing were adopted. For the first time, the rs13218408 polymorphism was found to be significantly associated with reduced Lp-PLA2 levels. We also confirmed the significant association of previously validated polymorphisms (rs1421378, rs1805018, rs16874954 and rs2216465), even after adjusting for traditional cardiovascular risk factors and for Bonferroni correction. Percentages of variance attributable to rs13218408 were 7.2% for activity and 13.3% for mass, and were secondary to those of rs16874954 (8.1% for activity and 16.9% for mass). A significant joint effect of rs13218408 and rs16874954 was observed on Lp-PLA2 activity (P = 0.058) and mass (P = 0.003), with their minor alleles together linking to the largest reduction in Lp-PLA2 levels (37.8% reduction in activity and 41.6% reduction in mass). Taken together, our findings show a significant association of a PLA2G7 polymorphism with Lp-PLA2 levels, which was previously unreported in any population. The functionality of this genetic variation deserves further investigations.
Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction
Authors: Ciemny Maciej Pawel , Debinski Aleksander , Paczkowska Marta , Kolinski Andrzej , Kurcinski Mateusz , Kmiecik Sebastian
Published: December 2016

Protein-peptide interactions are often associated with large-scale conformational changes that are difficult to study either by classical molecular modeling or by experiment. Recently, we have developed the CABS-dock method for flexible protein-peptide docking that enables large-scale rearrangements of the protein chain. In this study, we use CABS-dock to investigate the binding of the p53-MDM2 complex, an element of the cell cycle regulation system crucial for anti-cancer drug design. Experimental data suggest that p53-MDM2 binding is affected by significant rearrangements of a lid region - the N-terminal highly flexible MDM2 fragment; however, the details are not clear. The large size of the highly flexible MDM2 fragments makes p53-MDM2 intractable for exhaustive binding dynamics studies using atomistic models. We performed extensive dynamics simulations using the CABS-dock method, including large-scale structural rearrangements of MDM2 flexible regions. Without a priori knowledge of the p53 peptide structure or its binding site, we obtained near-native models of the p53-MDM2 complex. The simulation results match well the experimental data and provide new insights into the possible role of the lid fragment in p53 binding. The presented case study demonstrates that CABS-dock methodology opens up new opportunities for protein-peptide docking with large-scale changes of the protein receptor structure.
Cellular reactions to long-term volatile organic compound (VOC) exposures
Authors: Gostner Johanna M. , Zeisler Johannes , Alam Mohammad Tauqeer , Gruber Peter , Fuchs Dietmar , Becker Kathrin , Neubert Kerstin , Kleinhappl Markus , Martini Stefan , Überall Florian
Published: December 2016

Investigations of cellular processes initiated by volatile organic compounds (VOCs) are limited when modelling realistic long-term exposure scenarios at low concentrations. Exposure to indoor VOCs is associated with a range of adverse effects, but data on molecular changes at regulatory threshold limits are lacking. Activity analysis of VOC in vitro can be a valuable complement to inhalation toxicological evaluations. We developed an exposure platform that generates a stable VOC atmosphere and allows the exposure of cells for longer periods. Using formaldehyde as a model analyte, air-liquid interface cultured A549 lung epithelial cells were exposed to critical concentrations of 0.1 and 0.5 ppm for 3 days. Owing to the lack of known exposure biomarkers, we applied a genome-wide transcriptional analysis to investigate cellular responses at these sublethal concentrations. We demonstrate a minor overlap of differentially expressed transcripts for both treatment concentrations, which can be further analyzed for their use as exposure biomarkers. Moreover, distinct expression patterns emerge for 0.1 and 0.5 ppm formaldehyde exposure, which is reflected in significant enrichment of distinct biological processes. More specifically, metabolism of specific compound classes, lipid biosynthesis and lung-associated functions are affected by lower exposure levels and processes affecting proliferation and apoptosis dominate the higher exposure levels.
Hallucinations in schizophrenia and Parkinson’s disease: an analysis of sensory modalities involved and the repercussion on patients
Authors: Llorca P. M. , Pereira B. , Jardri R. , Chereau-Boudet I. , Brousse G. , Misdrahi D. , Fénelon G. , Tronche A.-M. , Schwan R. , Lançon C. , Marques A. , Ulla M. , Derost P. , Debilly B. , Durif F. , de Chazeron I.
Published: December 2016

Hallucinations have been described in various clinical populations, but they are neither disorder nor disease specific. In schizophrenia patients, hallucinations are hallmark symptoms and auditory ones are described as the more frequent. In Parkinson’s disease, the descriptions of hallucination modalities are sparse, but the hallucinations do tend to have less negative consequences. Our study aims to explore the phenomenology of hallucinations in both hallucinating schizophrenia patients and Parkinson’s disease patients using the Psycho-Sensory hAllucinations Scale (PSAS). The main objective is to describe the phenomena of these clinical symptoms in those two specific populations. Each hallucinatory sensory modality significantly differed between Parkinson’s disease and schizophrenia patients. Auditory, olfactory/gustatory and cœnesthetic hallucinations were more frequent in schizophrenia than visual hallucinations. The guardian angel item, usually not explored in schizophrenia, was described by 46% of these patients. The combination of auditory and visual hallucinations was the most frequent for both Parkinson’s disease and schizophrenia. The repercussion index summing characteristics of each hallucination (frequency, duration, negative aspects, conviction, impact, control and sound intensity) was always higher for schizophrenia. A broader view including widespread characteristics and interdisciplinary works must be encouraged to better understand the complexity of the process involved in hallucinations.
Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate
Authors: Soldovieri Maria Virginia , Ambrosino Paolo , Mosca Ilaria , De Maria Michela , Moretto Edoardo , Miceli Francesco , Alaimo Alessandro , Iraci Nunzio , Manocchio Laura , Medoro Alessandro , Passafaro Maria , Taglialatela Maurizio
Published: December 2016

Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K+ current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunits exerted dominant-negative effects when incorporated into heteromeric channels with Kv7.2 and/or Kv7.3 subunits. Increasing cellular PIP2 levels by co-expression of type 1γ PI(4)P5-kinase (PIP5K) partially recovered homomeric Kv7.2 R325G channel function. Currents carried by heteromeric channels incorporating Kv7.2 R325G subunits were more readily inhibited than wild-type channels upon activation of a voltage-sensitive phosphatase (VSP), and recovered more slowly upon VSP switch-off. These results reveal for the first time that a mutation-induced decrease in current sensitivity to PIP2 is the primary molecular defect responsible for Kv7.2-EE in individuals carrying the R325G variant, further expanding the range of pathogenetic mechanisms exploitable for personalized treatment of Kv7.2-related epilepsies.
Serbian Language version of the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up: Cross-Cultural Adaptation and Assessment of Reliability
Authors: Carakovac Mia , Jovanovic Jelena , Kalanj Marko , Rudic Nenad , Aleksic–Hil Olivera , Aleksic Branko , Villalobos Itzel Bustos , Kasuya Hideki , Ozaki Norio , Lecic–Tosevski Dusica , Pejovic–Milovancevic Milica
Published: December 2016

Early detection of Autism Spectrum Disorder (ASD) has proven to be of high significance, however there is a limited availability of ASD screening tools in Serbian language. In this study we aim to translate, assess reliability and, in part, test the applicability of Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT R/F) in Serbian Healthcare environment. We screened 128 children in three primary healthcare centres and 20 children in a tertiary psychiatric center, using M-CHAT R/F translated into Serbian language, between December 2014 and October 2015. At the end of the screening process 80% of participants in the risk group screened positive for ASD, while in the control group 4 (3.1%) participants screened positive, with a mean total scores of 8.25 and 0.66 respectively. The Cronbach’s α coefficient was 0.91 and Guttman’s λ6 was 0.93. Test – retest reliability was deemed as acceptable, and no significant correlation was found between M-CHAT-R/F scores and Epworth Sleepiness Scale for children scores. The Serbian version of the M-CHAT-R/F has shown satisfactory reliability. We can therefore assert that it is a reliable tool for identifying ASD and it can be used in clinical practice to improve early detection, assessment and treatment.
Defining an olfactory receptor function in airway smooth muscle cells
Authors: Aisenberg William H. , Huang Jessie , Zhu Wanqu , Rajkumar Premraj , Cruz Randy , Santhanam Lakshmi , Natarajan Niranjana , Yong Hwan Mee , De Santiago Breann , Oh Jung Jin , Yoon A-Rum , Panettieri Reynold A. , Homann Oliver , Sullivan John K. , Liggett Stephen B. , Pluznick Jennifer L. , An Steven S.
Published: December 2016

Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma.
Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine
Authors: Raeven René H. M. , Brummelman Jolanda , Pennings Jeroen L. A. , van der Maas Larissa , Tilstra Wichard , Helm Kina , van Riet Elly , Jiskoot Wim , van Els Cécile A. C. M. , Han Wanda G. H. , Kersten Gideon F. A. , Metz Bernard
Published: December 2016

The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice. The comparison revealed essential qualitative and quantitative differences with respect to immunogenicity and adverse effects for these vaccines. Both vaccines stimulated a mixed systemic Th1/Th2/Th17 response. Remarkably, omvPV evoked higher IgG levels, lower systemic pro-inflammatory cytokine responses and enhanced splenic gene expression than wPV. The omvPV-induced transcriptome revealed gene signatures of the IFN-signaling pathway, anti-inflammatory signatures that attenuate LPS responses, anti-inflammatory metabolic signatures, and IgG responses. Upon intranasal challenge, both immunized groups were equally efficient in clearingBordetella pertussisfrom the lungs. This study importantly shows that immunization with omvPV provides a milder inflammatory responses but with equal protection to bacterial colonization and induction of protective antibody and Th1/Th17 type immune responses compared to wPV. These results emphasize the potential of omvPV as a safe and effective next-generation pertussis vaccine.
Photocatalytic air-purification: a low-cost, real-time gas detection method
Authors: Keane Donal A. , Hamilton Niki , Gibson Lorraine T. , Pillai Suresh. C. , Holmes Justin D. , Morris Michael A.
Published: December 2016

This research demonstrates the use of a gas detector as a feasible alternative to the standardized analytical methods typically found in photocatalytic air-purification ISO standard tests and academic literature.
Protoporphyrin IX-modified chitosan-g-oligo(NiPAAm) polymeric micelles: from physical stabilization to permeability characterization in vitro
Authors: Schlachet Inbar , Sosnik Alejandro
Published: December 2016

Protoporphyrin IX was used to stabilize the polymeric micelles and study permeabilityin vitro.
A Cu(ii) complex targeting the translocator protein: in vitro and in vivo antitumor potential and mechanistic insights
Authors: Montagner D. , Fresch B. , Browne K. , Gandin V. , Erxleben A.
Published: December 2016

A Cu complex targeting the translocator protein induces a 98% reduction of tumor mass in a murine tumor model.
BiOBr nanoplates@TiO2 nanowires/carbon fiber cloth as a functional water transport network for continuous flow water purification
Authors: Mei Yan , Su Yanhui , Li Zheng , Bai Shiqi , Yuan Mengyu , Li Lu , Yan Zheng , Wu Jun , Zhu Lian-Wen
Published: December 2016

A novel BiOBr@TiO2/carbon hybrid framework as a continuous flow sunlight water purification system has been reported in the present work.
A unique dysprosium selenoarsenate(iii) exhibiting a photocurrent response and slow magnetic relaxation behavior
Authors: Zhou Jian , Zou Hua-Hong , Zhao Rongqing , Xiao Hong , Ding Qingran
Published: December 2016

A unique dysprosium selenoarsenate(iii) contains large oligomeric cluster [As3Se6]3−anions with binuclear dysprosium complexes as counterions, and exhibits a photocurrent response and slow magnetic relaxation behavior.
Physical and chemical properties of Cu(i) compounds with O and/or H
Authors: Li Yunguo , Korzhavyi Pavel A.
Published: December 2016

The electronic structure and chemical bonding of Cu(i) compounds with O and/or H are investigated using ab initio calculations based on density functional theory.
Holistic computational structure screening of more than 12 000 candidates for solid lithium-ion conductor materials
Authors: Sendek Austin D. , Yang Qian , Cubuk Ekin D. , Duerloo Karel-Alexander N. , Cui Yi , Reed Evan J.
Published: December 2016

We leverage available data and statistical learning methods to perform a holistic screening for promising new solid electrolytes.
The marriage and integration of nanostructures with different dimensions for synergistic electrocatalysis
Authors: Zhu Han , Gu Li , Yu Danni , Sun Yingjun , Wan Meng , Zhang Ming , Wang Lei , Wang Lina , Wu Weiwei , Yao Juming , Du Mingliang , Guo Shaojun
Published: December 2016

An effective strategy for the rational design of 3D architectures for superior electrocatalysis, through the integration of CNFs, CNTs and oxygen-deficient Mn3Co7–Co2Mn3O8 nanoparticles, has been demonstrated.
Morphology, structure, and metal binding mechanisms of biogenic manganese oxides in a superfund site treatment system
Authors: Duckworth O. W. , Rivera N. A. , Gardner T. G. , Andrews M. Y. , Santelli C. M. , Polizzotto M. L.
Published: December 2016

Manganese oxides, which may be biogenically produced in both pristine and contaminated environments, have a large affinity for many trace metals.
3D-QSAR predictions for bovine serum albumin–water partition coefficients of organic anions using quantum mechanically based descriptors
Authors: Linden Lukas , Goss Kai-Uwe , Endo Satoshi
Published: December 2016

The 3D-QSAR model predicts the bovine serum albumin–water partition coefficients for neutral and anionic chemicals influenced by steric effects.
Eukaryotic community diversity and spatial variation during drinking water production (by seawater desalination) and distribution in a full-scale network
Authors: Belila A. , El-Chakhtoura J. , Saikaly P. E. , van Loosdrecht M. C. M. , Vrouwenvelder J. S.
Published: December 2016

Characterization of eukaryotic community dominated by fungi for drinking water distribution network fed by reverse osmosis seawater desalination plant.
Phosphonium polymers for gene delivery
Authors: Loczenski Rose Vanessa , Mastrotto Francesca , Mantovani Giuseppe
Published: December 2016

Phosphonium salt-containing polymers have very recently started to emerge as attractive materials for engineering non-viral gene delivery systems.
Ban+2Znn(BO3)n(B2O5)Fn(n = 1, 2): new members of the zincoborate fluoride series with two kinds of isolated B–O units
Authors: Mutailipu Miriding , Su Xin , Zhang Min , Yang Zhihua , Pan Shilie
Published: December 2016

Two new zincoborate fluorides were firstly reported containing isolated [BO3]3−and [B2O5]4−groups, which are the first examples of two kinds of isolated B–O groups that coexist in one zincoborate halide.
Unprecedented phthalocyanine–porphyrin-fused oligomers with induced chirality nature
Authors: Zhang Yuehong , Zhao Luyang , Wang Kang , Jiang Jianzhuang
Published: December 2016

As the thus-far reported largest chiral tetrapyrrole-based conjugated systems, phthalocyanine–porphyrin-fused oligomers with induced chirality nature have been designed and isolated.
Fluorine-tin oxide (FTO) electrode modified with platinum nanoparticles dispersed into montmorillonite clay as an effective and low cost catalyst for ethanol electrooxidation
Authors: Saghi Esmat , Rounaghi Gholam Hossein , Sarafraz-Yazdi Ali , Razavipanah Iman , Moosavi Parisa Mirhoseini
Published: December 2016

This work demonstrates the use of montmorillonite (MMT) clay minerals as an effective and low cost catalyst support for Pt nanoparticles for electrocatalytic oxidation of ethanol molecules.
A novel phased array antenna system for microwave-assisted organic syntheses under waveguideless and applicatorless setup conditions
Authors: Horikoshi Satoshi , Yamazaki Satoshi , Narita Atsushi , Mitani Tomohiko , Shinohara Naoki , Serpone Nick
Published: December 2016

An experimental microwave phased array antenna system to carry out organic syntheses and materials processing under waveguideless and applicatorless conditions is reported.
Poly(3,4-ethylenedioxythiophene) (PEDOT) infused TiO2nanofibers: the role of hole transport layer in photocatalytic degradation of phenazopyridine as a pharmaceutical contaminant
Authors: Liu Jian , McCarthy Danielle L. , Tong Linyue , Cowan Michael J. , Kinsley John M. , Sonnenberg Laura , Skorenko Kenneth H. , Boyer Steven M. , DeCoste Jared B. , Bernier William E. , Jones Wayne E.
Published: December 2016

PEDOT infused TiO2nanofibers exhibit enhanced photocatalytic performance by improved hole transfer for the degradation of PAP.
Reduced use of glucose by normoxic cow's mammary gland under acute inflammation: an example of homeostatic aerobic glycolysis
Authors: Silanikove Nissim , Shapiro Fira , Merin Uzi , Lavon Yaniv , Blum Shlomo E. , Leitner Gabriel
Published: December 2016

The concentration of glucose and glucose-derived carbons in milk reflect their concentrations in the mammary epithelial cell cytosol.
Metabolic regulatory network alterations reveal different therapeutic effects of cisplatin and Rhizoma paridis saponins in Lewis pulmonary adenoma mice
Authors: Qiu Peiyu , Man Shuli , Yang He , Liu Yuanxue , Liu Zhen , Ma Long , Yu Peng , Gao Wenyuan
Published: December 2016

Metabonomics is used to compare the metabolic profiling of RPS and DDP in Lewis pulmonary adenoma mice; RPS is found to be a potent anticancer agent through inhibiting cancer cellular metabolism to suppress metastases in murine lung adenocarcinoma.
A nanoporous carbon material derived from pomelo peels as a fiber coating for solid-phase microextraction
Authors: Wang Wenchang , Zhang Lihong , Li Zhi , Zhang Shuaihua , Wang Chun , Wang Zhi
Published: December 2016

A novel nanoporous carbon derived from a biomass source was prepared and used as an SPME fiber coating.
Near-field absorption imaging by a Raman nano-light source
Authors: Kato Ryo , Saito Yuika , Verma Prabhat
Published: December 2016

We demonstrate nano-scale absorption imaging by using a novel Raman light source.
Nanomaterials as a game changer in the management and treatment of diabetic foot ulcers
Authors: Vellayappan M. V. , Jaganathan S. K. , Manikandan A.
Published: December 2016

Nanoengineered biomaterials have tremendously improved the range of tools utilized for the control of as well as acceleration of healing of diabetic foot ulcers (DFU) over the last few decades.
Continuous variables logic via coupled automata using a DNAzyme cascade with feedback
Authors: Lilienthal S. , Klein M. , Orbach R. , Willner I. , Remacle F. , Levine R. D.
Published: December 2016

Implementing an AND gate with stochastic input and output by the hybridization of a DNAzyme and its hairpin substrate.
In situ observation of reactive oxygen species forming on oxygen-evolving iridium surfaces
Authors: Pfeifer Verena , Jones Travis E. , Velasco Vélez Juan J. , Arrigo Rosa , Piccinin Simone , Hävecker Michael , Knop-Gericke Axel , Schlögl Robert
Published: December 2016

In situ XAS measurements reveal that electron-deficient oxygen species form during OER on IrOx and correlate with catalytic activity.
Differential‐mode bandpass filter on microstrip line with wideband common‐mode suppression
Authors: Chen Dong , Zhu Lei , Bu Huizheng , Cheng Chonghu
Published: December 2016

A novel differential‐mode (DM) bandpass filter (BPF) on microstrip‐line topology with wideband common‐mode (CM) suppression is presented. The DM BPF is composed of a pair of half‐wavelength (λ/2) uniform impedance resonators and two coupled‐line sections as feeding scheme. By installing an open‐circuited stub in the middle of the coupled‐line section, spurious CM response can be tremendously suppressed over a wide band. Thus, wideband CM suppression is realised in and beyond core DM passband. Finally, a DM BPF is designed and fabricated to support the proposed design concept.
Energy‐efficient power allocation and mode selection in hybrid multi‐cell architecture with limited backhaul capacity
Authors: Ma Yue , Wang Xin , Ge Songhu , Li Wei , Wei Jibo
Published: December 2016

This study addresses the problem of power allocation and mode selection in a hybrid coordinated multi‐cell transmission system with limited backhaul capacity. The power consumption is considered as the extra expense due to data exchange via backhaul links. A novel hybrid multi‐cell scheme is presented, in which each mobile station (MS) can dynamically select either interference channel or multi‐cell multi‐input and multi‐output cooperation mode. To maximise energy efficiency (EE), the optimal power allocation scheme with low complexity is proposed. Moreover, the authors propose an energy‐efficient mode selection metric for each MS, which reflects both benefits and extra expense brought by the selected cooperation mode. Based on the proposed metric, the optimal mode selection strategy maximising EE is obtained. Numerical results show that the hybrid multi‐cell scheme outperforms the traditional single cooperation mode scheme in terms of EE.
A Meta-analysis of Functional Outcomes in Patient-Specific Instrumented Knee Arthroplasty
Authors: Akinyooye Deji , Hossain Fahad , Mannan Ashim
Published: December 2016

Alignment data in patient-specific instrumented (PSI) knee arthroplasty have been examined in several meta-analyses, with demonstration of comparative but not improved restitution of a neutral mechanical axis and favorable outcomes in femoral implant axial alignment. To date, no comprehensive synthesis of data has been conducted specifically for functional outcomes. Relevant databases were searched according to Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines during the period 2000 to 2015 of Levels 1 and 2 studies comparing functional outcomes of patient-specific instrumentation (PSI) versus conventional instrumentation. Outcomes of interest included postoperative Knee Society score (KSS) (function), KSS (knee), range of movement (ROM), Oxford knee scores (OKS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Five randomized controlled trials and three prospective-comparative studies were included reporting on a total of 828 knees. All eight studies reported postoperative KSS (function) and seven studies reported KSS (knee). Three studies reported postoperative OKS, four documented ROM, and two reported WOMAC scores. Meta-analysis demonstrated equivalent KSS (function) scores 3 months postsurgery (Z = 1.71, p = 0.09). In addition, no significant differences were found for KSS (function) at 6 months (Z = 0.51, p = 0.61) or 12 to 24 months postsurgery (Z = 0.05, p = 0.96). In addition, no significant differences were found between PSI and conventional instrumentation for postoperative KSS (knee), ROM, or OKS. In summary, this systematic review and meta-analysis demonstrates no conclusive evidence for or against PSI when considering short-term functional outcomes. Further high-quality studies are required to investigate both mid- and long-term outcomes as well as survivorship data.