bluuebunny/crossref_metadata_2025_split huggingface dataset:
SALL4 promotes gastric cancer progression through activating CD44 expression
Authors: Yuan X , Zhang X , Zhang W , Liang W , Zhang P , Shi H , Zhang B , Shao M , Yan Y , Qian H , Xu W 
Published: November 2016

AbstractThe stem cell factor SALL4 (Sal-like protein 4) plays important roles in the development and progression of cancer. SALL4 is critically involved in tumour growth, metastasis and therapy resistance. However, the underlying mechanisms responsible for the oncogenic roles of SALL4 have not been well characterized. In this study, we demonstrated that SALL4 knockdown by short hairpin RNA greatly inhibited the proliferation, migration and invasion of gastric cancer cells. We further confirmed the inhibitory effects of SALL4 knockdown on gastric cancer cells by using a tetracycline-inducible system. Mechanistically, SALL4 knockdown downregulated the expression of CD44. The results of luciferase assay and chromatin immunoprecipitation study showed that SALL4 bound to CD44 promoter region and transcriptionally activated CD44. The results of rescue study revealed that CD44 overexpression antagonized SALL4 knockdown-mediated inhibition of gastric cancer cell proliferation, migration, and invasion in vitro and gastric cancer growth in vivo. Collectively, our findings indicate that SALL4 promotes gastric cancer progression through directly activating CD44 expression, which suggests a novel mechanism for the oncogenic roles of SALL4 in gastric cancer and represents a new target for gastric cancer therapy.
3-dimensional electron microscopic imaging of the zebrafish olfactory bulb and dense reconstruction of neurons
Authors: Wanner Adrian A. , Genoud Christel , Friedrich Rainer W. 
Published: November 2016

AbstractLarge-scale reconstructions of neuronal populations are critical for structural analyses of neuronal cell types and circuits. Dense reconstructions of neurons from image data require ultrastructural resolution throughout large volumes, which can be achieved by automated volumetric electron microscopy (EM) techniques. We used serial block face scanning EM (SBEM) and conductive sample embedding to acquire an image stack from an olfactory bulb (OB) of a zebrafish larva at a voxel resolution of 9.25×9.25×25 nm3. Skeletons of 1,022 neurons, 98% of all neurons in the OB, were reconstructed by manual tracing and efficient error correction procedures. An ergonomic software package, PyKNOSSOS, was created in Python for data browsing, neuron tracing, synapse annotation, and visualization. The reconstructions allow for detailed analyses of morphology, projections and subcellular features of different neuron types. The high density of reconstructions enables geometrical and topological analyses of the OB circuitry. Image data can be accessed and viewed through the neurodata web services (http://www.neurodata.io). Raw data and reconstructions can be visualized in PyKNOSSOS.
A new method for measuring lung deposition efficiency of airborne nanoparticles in a single breath
Authors: Jakobsson Jonas K. F. , Hedlund Johan , Kumlin John , Wollmer Per , Löndahl Jakob 
Published: November 2016

AbstractAssessment of respiratory tract deposition of nanoparticles is a key link to understanding their health impacts. An instrument was developed to measure respiratory tract deposition of nanoparticles in a single breath. Monodisperse nanoparticles are generated, inhaled and sampled from a determined volumetric lung depth after a controlled residence time in the lung. The instrument was characterized for sensitivity to inter-subject variability, particle size (22, 50, 75 and 100 nm) and breath-holding time (3–20 s) in a group of seven healthy subjects. The measured particle recovery had an inter-subject variability 26–50 times larger than the measurement uncertainty and the results for various particle sizes and breath-holding times were in accordance with the theory for Brownian diffusion and values calculated from the Multiple-Path Particle Dosimetry model. The recovery was found to be determined by residence time and particle size, while respiratory flow-rate had minor importance in the studied range 1–10 L/s. The instrument will be used to investigate deposition of nanoparticles in patients with respiratory disease. The fast and precise measurement allows for both diagnostic applications, where the disease may be identified based on particle recovery, and for studies with controlled delivery of aerosol-based nanomedicine to specific regions of the lungs.
Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations
Authors: Sun Daphne , Dalin Simona , Hemann Michael T. , Lauffenburger Douglas A. , Zhao Boyang 
Published: November 2016

AbstractRecent drug discovery and development efforts have created a large arsenal of targeted and chemotherapeutic drugs for precision medicine. However, drug resistance remains a major challenge as minor pre-existing resistant subpopulations are often found to be enriched at relapse. Current drug design has been heavily focused on initial efficacy, and we do not fully understand the effects of drug selective pressure on long-term drug resistance potential. Using a minimal two-population model, taking into account subpopulation proportions and growth/kill rates, we modeled long-term drug treatment and performed parameter sweeps to analyze the effects of each parameter on therapeutic efficacy. We found that drugs with the same overall initial kill may exert differential selective pressures, affecting long-term therapeutic outcome. We validated our conclusions experimentally using a preclinical model of Burkitt’s lymphoma. Furthermore, we highlighted an intrinsic tradeoff between drug-imposed overall selective pressure and rate of adaptation. A principled approach in understanding the effects of distinct drug selective pressures on short-term and long-term tumor response enables better design of therapeutics that ultimately minimize relapse.
The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy
Authors: Choi Chang Soon , Gonzales Edson Luck , Kim Ki Chan , Yang Sung Min , Kim Ji-Woon , Mabunga Darine Froy , Cheong Jae Hoon , Han Seol-Heui , Bahn Geon Ho , Shin Chan Young 
Published: November 2016

AbstractAutism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.
The PTEN phosphatase functions cooperatively with the Fanconi anemia proteins in DNA crosslink repair
Authors: Vuono Elizabeth A. , Mukherjee Ananda , Vierra David A. , Adroved Morganne M. , Hodson Charlotte , Deans Andrew J. , Howlett Niall G. 
Published: November 2016

AbstractFanconi anemia (FA) is a genetic disease characterized by bone marrow failure and increased cancer risk. The FA proteins function primarily in DNA interstrand crosslink (ICL) repair. Here, we have examined the role of the PTEN phosphatase in this process. We have established that PTEN-deficient cells, like FA cells, exhibit increased cytotoxicity, chromosome structural aberrations, and error-prone mutagenic DNA repair following exposure to ICL-inducing agents. The increased ICL sensitivity of PTEN-deficient cells is caused, in part, by elevated PLK1 kinase-mediated phosphorylation of FANCM, constitutive FANCM polyubiquitination and degradation, and the consequent inefficient assembly of the FA core complex, FANCD2, and FANCI into DNA repair foci. We also establish that PTEN function in ICL repair is dependent on its protein phosphatase activity and ability to be SUMOylated, yet is independent of its lipid phosphatase activity. Finally, via epistasis analysis, we demonstrate that PTEN and FANCD2 function cooperatively in ICL repair.
A Novel Non-Peptidic Agonist of the Ghrelin Receptor with Orexigenic Activity In vivo
Authors: Pastor-Cavada Elena , Pardo Leticia M. , Kandil Dalia , Torres-Fuentes Cristina , Clarke Sarah L. , Shaban Hamdy , McGlacken Gerard P. , Schellekens Harriet 
Published: November 2016

AbstractLoss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.
Global Changes in Lipid Profiles of Mouse Cortex, Hippocampus, and Hypothalamus Upon p53 Knockout
Authors: Lee Sang Tak , Lee Jong Cheol , Kim Jong Whi , Cho Soo Young , Seong Je Kyung , Moon Myeong Hee 
Published: November 2016

AbstractComprehensive lipidomic profiling in three different brain tissues (cortex, hippocampus, and hypothalamus) of mouse with p53 deficiency was performed by nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS) and the profile was compared with that of the wild type. p53 gene is a well-known tumour suppressor that prevents genome mutations that can cause cancers. More than 300 lipids (among 455 identified species), including phospholipids (PLs), sphingolipids, ceramides (Cers), and triacylglycerols (TAGs) were quantitatively analysed by selective reaction monitoring (SRM) of nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUPLC-ESI-MS/MS). Among the three different neural tissues, hypothalamus demonstrated the most evident lipid profile changes upon p53 knockout. Alterations of PLs containing acyl chains of docosahexaenoic acid and arachidonic acid (highly enriched polyunsaturated fatty acids in the nervous system) were examined in relation to cell apoptosis upon p53 knockout. Comparison between sphingomyelins (SMs) and Cers showed that the conversion of SM to Cer did not effectively progress in the hypothalamus, resulting in the accumulation of SMs, possibly due to the inhibition of apoptosis caused by the lack of p53. Furthermore, TAGs were considerably decreased only in the hypothalamus, indicative of lipolysis that led to substantial weight loss of adipose tissue and muscles.
In ovo uptake, metabolism, and tissue-specific distribution of chiral PCBs and PBDEs in developing chicken embryos
Authors: Li Zong-Rui , Luo Xiao-Jun , Huang Li-Qian , Mai Bi-Xian 
Published: November 2016

AbstractFertilized chicken eggs were injected with environmental doses of 4 chiral polychlorinated biphenyls (PCBs) and 8 polybrominated biphenyl ethers (PBDEs) to investigate their uptake, metabolism in the embryo, and distribution in the neonate chicken. PCB95 uptake was the most efficient (80%) whereas BDE209 was the least (56%). Embryos metabolized approximately 52% of the PCBs absorbed. Though some degree of metabolism in the first 18 days, most of the PCBs and PBDEs was metabolized in the last three days, when BDE85, 99, 153, and 209 decrease by 11–37%. Enantioselective metabolism of the (+) enantiomers of PCB95, 149, and 132 and the (−) enantiomer of PCB91 was observed. The enantioselective reactivity was higher with the two penta-PCBs than the two tetra-PCBs. Liver, exhibited high affinity for high lipophilic chemicals, enrich all chemicals that was deflected in other tissues except for some special chemicals in a given tissues. Lipid composition, time of organ formation, and metabolism contribute to the distribution of chemicals in the neonate chicken. The result of this study will improve our understanding on the fate and potential adverse effects of PCBs and PBDEs in the neonate chicken.
An active IGF-1R-AKT signaling imparts functional heterogeneity in ovarian CSC population
Authors: Singh Ram K. , Dhadve Ajit , Sakpal Asmita , De Abhijit , Ray Pritha 
Published: November 2016

AbstractDeregulated IGF-1R-AKT signaling influences multiple nodes of cancer cell physiology and assists in migration, metastasis and acquirement of radio/chemoresistance. Enrichment of cancer stem cells (CSC) positively correlates with radio/chemoresistance development in various malignancies. It is unclear though, how IGF-1R-AKT signalling shapes CSC functionality especially in ovarian cancer. Previously we showed that upregulated IGF-1R expression is essential to initiate platinum-taxol resistance at early stage which declines with elevated levels of activated AKT at late resistant stage in ovarian cancer cells. Here, we investigated the effect of this oscillatory IGF-1R-AKT signalling upon CSC functionality during generation of chemoresistance. While gradual increase in CSC properties from early (ER) to late (LR) resistant stages was observed in three different (cisplatin/paclitaxel/cisplatin-paclitaxel) cellular models created in two ovarian cancer cell lines, the stemness gene expressions (oct4/sox2/nanog) reached a plateau at early resistant stages. Inhibition of IGF-1R only at ER and AKT inhibition only at LR stages significantly abrogated the CSC phenotype. Interestingly, real time bioluminescence imaging showed CSCs of ER stages possessed faster tumorigenic potential than CSCs belonging to LR stages. Together, our data suggest that IGF-1R-AKT signalling imparts functional heterogeneity in CSCs during acquirement of chemoresistance in ovarian carcinoma.
Sequencing of long stretches of repetitive DNA
Authors: De Bustos Alfredo , Cuadrado Angeles , Jouve Nicolás 
Published: November 2016

AbstractRepetitive DNA is widespread in eukaryotic genomes, in some cases making up more than 80% of the total. SSRs are a type of repetitive DNA formed by short motifs repeated in tandem arrays. In some species, SSRs may be organized into long stretches, usually associated with the constitutive heterochromatin. Variation in repeats can alter the expression of genes, and changes in the number of repeats have been linked to certain human diseases. Unfortunately, the molecular characterization of these repeats has been hampered by technical limitations related to cloning and sequencing. Indeed, most sequenced genomes contain gaps owing to repetitive DNA-related assembly difficulties. This paper reports an alternative method for sequencing of long stretches of repetitive DNA based on the combined use of 1) a linear vector to stabilize the cloning process, and 2) the use of exonuclease III for obtaining progressive deletions of SSR-rich fragments. This strategy allowed the sequencing of a fragment containing a stretch of 6.2 kb of continuous SSRs. To demonstrate that this procedure can sequence other kinds of repetitive DNA, it was used to examine a 4.5 kb fragment containing a cluster of 15 repeats of the 5S rRNA gene of barley.
Comparative morphological trade-offs between pre- and post-copulatory sexual selection in Giant hissing cockroaches (Tribe: Gromphadorhini)
Authors: Durrant Kate L. , Skicko Ian M. , Sturrock Craig , Mowles Sophie L. 
Published: November 2016

AbstractSperm competition theory predicts that animals face a trade-off between investment in weaponry and investment in ejaculate composition. Within the Madagascan giant hissing cockroaches (Tribe Gromphadorhini) differences in morphology exist that may indicate differing strategies of male-male competition. We compared relative pronotal horn length using high-resolution X-ray CT scanning data, relative testes mass, and male-male agonistic behaviour between two species of hissing cockroaches, Gromphadorhina oblongonota and Aeluropoda insignis. The gross morphology and behaviour of these two species indicated that G. oblongonota is selected for pre-copulatory mate acquisition and that A. insignis is selected for post-copulatory sperm competition. We found evidence for a trade-off when investing in testes mass vs. horn length between the species. The large, aggressive G. oblongonota follows a strategy of greater investment in weapons at the expense of testes mass while the smaller, less-aggressive A. insignis invests in relatively greater testes mass and less in pronotal weapon length. We also found evidence of a trade-off within each species, where individuals invest more heavily in weapon length at the expense of testes mass. These findings support the predictions of pre- and post-copulatory competitive investment trade-offs for a relatively understudied Tribe of cockroaches.
Synthesis of TiO2@C nanospheres with excellent electrochemical properties
Authors: Ding Jing , Gao Xian , Cha Limei , Cai Mei-Qiu , Ma Jianmin 
Published: November 2016

TiO2@C nanospheres could exhibit a discharge capacity of 286.5 mA h g−1 at 100 mA g−1 after 200 cycles.
Voltage-gated sodium channels and pain-related disorders
Authors: Kanellopoulos Alexandros H. , Matsuyama Ayako 
Published: November 2016

Voltage-gated sodium channels (VGSCs) are heteromeric transmembrane protein complexes. Nine homologous members, SCN1A–11A, make up the VGSC gene family. Sodium channel isoforms display a wide range of kinetic properties endowing different neuronal types with distinctly varied firing properties. Among the VGSCs isoforms, Nav1.7, Nav1.8 and Nav1.9 are preferentially expressed in the peripheral nervous system. These isoforms are known to be crucial in the conduction of nociceptive stimuli with mutations in these channels thought to be the underlying cause of a variety of heritable pain disorders. This review provides an overview of the current literature concerning the role of VGSCs in the generation of pain and heritable pain disorders.
Long non-coding RNAs (lncRNAs) in skeletal and cardiac muscle: potential therapeutic and diagnostic targets?
Authors: McMullen Julie R. , Drew Brian G. 
Published: November 2016

The recent discovery that thousands of RNAs are transcribed by the cell but are never translated into protein, highlights a significant void in our current understanding of how transcriptional networks regulate cellular function. This is particularly astounding when we consider that over 75% of the human genome is transcribed into RNA, but only approximately 2% of RNA is translated into known proteins. This raises the question as to what function the other so-called ‘non-coding RNAs’ (ncRNAs) are performing in the cell. Over the last decade, an enormous amount of research has identified several classes of ncRNAs, predominantly short ncRNAs (&lt;200 nt) that have been confirmed to have functional significance. Recent advances in sequencing technology and bioinformatics have also allowed for the identification of a novel class of ncRNAs, termed long ncRNA (lncRNA) (&gt;200 nt). Several studies have recently shown that long non-coding RNAs (lncRNAs) are associated with tissue development and disease, particularly in cell types that undergo differentiation such as stem cells, cancer cells and striated muscle (skeletal/cardiac). Therefore, understanding the function of these lncRNAs and designing strategies to detect and manipulate them, may present novel therapeutic and diagnostic opportunities. This review will explore the current literature on lncRNAs in skeletal and cardiac muscle and discuss their recent implication in development and disease. Lastly, we will also explore the possibility of using lncRNAs as therapeutic and diagnostic tools and discuss the opportunities and potential shortcomings to these applications.
Consent, Refusal, and Waivers in Patient-Centered Dysphagia Care: Using Law, Ethics, and Evidence to Guide Clinical Practice
Authors: Horner Jennifer , Modayil Maria , Chapman Laura Roche , Dinh An 
Published: November 2016

PurposeWhen patients refuse medical or rehabilitation procedures, waivers of liability have been used to bar future lawsuits. The purpose of this tutorial is to review the myriad issues surrounding consent, refusal, and waivers. The larger goal is to invigorate clinical practice by providing clinicians with knowledge of ethics and law. This tutorial is for educational purposes only and does not constitute legal advice.MethodThe authors use a hypothetical case of a “noncompliant” individual under the care of an interdisciplinary neurorehabilitation team to illuminate the ethical and legal features of the patient–practitioner relationship; the elements of clinical decision-making capacity; the duty of disclosure and the right of informed consent or informed refusal; and the relationship among noncompliance, defensive practices, and iatrogenic harm. We explore the legal question of whether waivers of liability in the medical context are enforceable or unenforceable as a matter of public policy.ConclusionsSpeech-language pathologists, among other health care providers, have fiduciary and other ethical and legal obligations to patients. Because waivers try to shift liability for substandard care from health care providers to patients, courts usually find waivers of liability in the medical context unenforceable as a matter of public policy.