julilili42/papers huggingface dataset:
Mutation Frequency of the Major Frontotemporal Dementia Genes, MAPT, GRN and C9ORF72 in a Turkish Cohort of Dementia Patients
2016-09-15

'Microtubule-associated protein tau' (MAPT), 'granulin' (GRN) and 'chromosome 9 open reading frame72' (C9ORF72) gene mutations are the major known genetic causes of frontotemporal dementia (FTD). Recent studies suggest that mutations in these genes may also be associated with other forms of dementia. Therefore we investigated whether MAPT, GRN and C9ORF72 gene mutations are major contributors to dementia in a random, unselected Turkish cohort of dementia patients. A combination of whole-exome sequencing, Sanger sequencing and fragment analysis/Southern blot was performed in order to identify pathogenic mutations and novel variants in these genes as well as other FTD-related genes such as the 'charged multivesicular body protein 2B' (CHMP2B), the 'FUS RNA binding protein' (FUS), the 'TAR DNA binding protein' (TARDBP), the 'sequestosome1' (SQSTM1), and the 'valosin containing protein' (VCP). We determined one pathogenic MAPT mutation (c.1906C>T, p.P636L) and one novel missense variant (c.38A>G, p.D13G). In GRN we identified a probably pathogenic TGAG deletion in the splice donor site of exon 6. Three patients were found to carry the GGGGCC expansions in the non-coding region of the C9ORF72 gene. In summary, a complete screening for mutations in MAPT, GRN and C9ORF72 genes revealed a frequency of 5.4% of pathogenic mutations in a random cohort of 93 Turkish index patients with dementia.
Alkaline Cytosolic pH and High Sodium Hydrogen Exchanger 1 (NHE1) Activity in Th9 Cells
2016-09-15

CD4<sup>+</sup> T helper 9 (Th9) cells are a newly discovered Th cell subset that produce the pleiotropic cytokine IL-9. Th9 cells can protect against tumors and provide resistance against helminth infections. Given their pivotal role in the adaptive immune system, understanding Th9 cell development and the regulation of IL-9 production could open novel immunotherapeutic opportunities. The Na<sup>+</sup>/H<sup>+</sup> exchanger 1 (NHE1; gene name Slc9α1)) is critically important for regulating intracellular pH (pH<sub>i</sub>), cell volume, migration, and cell survival. The pH<sub>i</sub> influences cytokine secretion, activities of membrane-associated enzymes, ion transport, and other effector signaling molecules such as ATP and Ca<sup>2+</sup> levels. However, whether NHE1 regulates Th9 cell development or IL-9 secretion has not yet been defined. The present study explored the role of NHE1 in Th9 cell development and function. Th cell subsets were characterized by flow cytometry and pH<sub>i</sub> was measured using 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-acetoxymethyl ester (BCECF-AM) dye. NHE1 functional activity was estimated from the rate of realkalinization following an ammonium pulse. Surprisingly, in Th9 cells pH<sub>i</sub> and NHE1 activity were significantly higher than in all other Th cell subsets (Th1/Th2/Th17 and induced regulatory T cells (iTregs)). NHE1 transcript levels and protein abundance were significantly higher in Th9 cells than in other Th cell subsets. Inhibition of NHE1 by siRNA-NHE1 or with cariporide in Th9 cells down-regulated IL-9 and ATP production. NHE1 activity, Th9 cell development, and IL-9 production were further blunted by pharmacological inhibition of protein kinase Akt1/Akt2. Our findings reveal that Akt1/Akt2 control of NHE1 could be an important physiological regulator of Th9 cell differentiation, IL-9 secretion, and ATP production.
1,2‐Annulated Sugars: Synthesis of Polyhydroxylated 2,10‐Dioxadecalins with β‐manno Configuration
2016-09-15

A new synthetic route to 1,2‐pyran‐annulated O ‐glycosides (pyranopyrans) with β‐ manno configuration is presented. Starting from a benzyl‐protected allyl β‐2‐uloside obtained by C 2‐oxidation from the corresponding allyl glucoside, vinylation and ring‐closing metathesis provided a bicyclic alkene as a key substrate. Optimized reaction conditions involving the 2‐uloside were required to circumvent the formation of the unwanted 3,2‐enolone. Subsequent stereoselective alkene dihydroxylations were investigated and are presented. Diastereoselective catalytic osmoylation afforded the bicyclic β‐mannoside with syn ‐diol configuration. In contrast, a sequence featuring a directed vanadium‐catalyzed alkene epoxidation and epoxide opening provided the corresponding 2,10‐dioxadecalin target compound with trans ‐diol configuration. X‐ray crystallography was employed to study the molecular structure of the target compound with syn ‐diol configuration. In addition, the molecular packing and hydrogen‐bonding interactions of the hydroxy‐rich molecule were examined.
First record of fossil Ophisaurus (Anguimorpha, Anguidae) from Asia
2016-09-15

Citation for this article: Vasilyan, D., M. Böhme, and J. Klembara. 2016. First record of fossil Ophisaurus (Anguimorpha, Anguidae) from Asia. Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2016.1219739.
A Late Middle Palaeolithic assemblage containing Levallois and bifacial objects from Saône-et-Loire, France: GH 3 at Grotte de la Verpillière II à Germolles
2016-09-15

The site of Grotte de la Verpillière II, a rock shelter and corresponding cave tunnel, is situated in a cliff face of an Oxfordian massive, around 10 km West of Chalon-sur-Saône in Eastern France. The excavation at this site has recovered Middle Palaeolithic assemblages in three stratified sedimentological units. The richest of these assemblages derives from Geological Horizon (GH) 3 and is discussed here. It is preliminarily attributed to a Late Middle Palaeolithic context of OIS 3 to 4 using radiometric-dating techniques.The assemblage combines Levallois reduction, bifacial objects and diverse ‘opportunistic’ reduction strategies. The Levallois reduction shows a high level of raw-material economy in the use of raw pieces and blanks whose morphology is close to the shape of desired configured cores. Other reduction strategies show a wider range of approaches to blank production. Bifacial objects include but are not limited to Keilmesser with tranchet blows. The condition of objects from GH 3 range from unused raw pieces, tested raw pieces, configured and exhausted cores, correction and central flakes, as well as some heated objects, frost shards, and debris. The majority of raw materials derive from sources nearby, but were clearly transported to the site. Only some pieces show evidence for transport of up to 100 km from source to site. The presence of specific reduction strategies on bifacial objects and the existence of tranchet-blow modification provide support for the attribution of the assemblage to the Keilmessergruppen assemblages from Central Europe.
The “Big‐Bang” for modern glial biology: Translation and comments on Pío del Río‐Hortega 1919 series of papers on microglia
2016-09-16

The word “glia” was coined in the mid‐19th century and defined as “the nerve glue”. For decades, it was assumed to be a uniform matrix, until cell theorists raised the “neuron doctrine” which stipulated that nervous tissue was composed of individual cells. The term “astrocytes” was introduced in the late 19th century as a synonym for glial cells, but it was Santiago Ramón y Cajal who defined a “third element” distinct from glial cells (astrocytes) and neurons. It was not until 1919 when Pío del Río‐Hortega, an alumnus of the Cajal School, introduced the modern terms we use today, and thoroughly described both “oligodendrocytes” and “microglia” to clearly distinguish them from astrocytes. In a series of four papers published that year in Spanish, Río‐Hortega described the distribution and morphological phenotype of microglia. He also noted that these cells were the origin of the rod cells described earlier in pathologic tissue, and recognized that resting microglia transformed into an ameboid phenotype in different types of brain diseases and pathologies. He also noted the mesodermal origin of these cells and recognized their phagocytic capacity. We here provide the first English translation of these landmark series of papers, which paved the way for modern glial research. To heighten the value and accessibility of these classic papers and their original figures, an introduction to this critical period of neuroscience is provided, along with unpublished photographs. By adding comments to the translated text, we provide sufficient context so that contemporary scientists may fully appreciate it. GLIA 2016;64:1801–1840
Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker
2016-09-16

1615EpCAM133 combines improved induction of ADCC with enhanced proliferation, limited cytokine response, and prolonged survival and proliferation of NK cells. By linking scFv-related targeting of carcinoma and CSCs with a sustaining IL-15 signal, our new construct shows great promise to target cancer and CSCs.
Visualizing Epithelial–Mesenchymal Transition Using the Chromobody Technology
2016-09-16

Abstract The epithelial–mesenchymal transition (EMT) is a complex cellular program involved in the progression of epithelial cancers to a metastatic stage. Along this process, epithelial traits are repressed in favor of a motile mesenchymal phenotype. A detailed characterization and monitoring of EMT-related processes is required for the design of screening strategies needed to develop novel antimetastatic therapies. Overexpression of the canonical EMT biomarker vimentin correlates with increased tumor growth and invasiveness, as well as with reduced patient survival across various epithelial cancers. Moreover, recent findings have demonstrated an active role of vimentin in regulating and reorganizing the cellular architecture toward a migratory and invasive phenotype. However, current studies suffer from a lack of appropriate methods to trace the induction and dynamics of vimentin in cell-based assays. Recently, we have reported a novel intrabody (chromobody)–based approach to study the spatiotemporal organization of endogenous vimentin upon induction of EMT by high-content imaging. In this review, we discuss the relevance of the chromobody technology with regard to the visualization of EMT-related processes in living systems. Cancer Res; 76(19); 5592–6. ©2016 AACR.
A Systematic Investigation of Accuracy and Response Time Based Measures Used to Index ANS Acuity
2016-09-16

The approximate number system (ANS) was proposed to be a building block for later mathematical abilities. Several measures have been used interchangeably to assess ANS acuity. Some of these measures were based on accuracy data, whereas others relied on response time (RT) data or combined accuracy and RT data. Previous studies challenged the view that all these measures can be used interchangeably, because low correlations between some of the measures had been observed. These low correlations might be due to poor reliability of some of the measures, since the majority of these measures are mathematically related. Here we systematically investigated the relationship between common ANS measures while avoiding the potential confound of poor reliability. Our first experiment revealed high correlations between all accuracy based measures supporting the assumption that all of them can be used interchangeably. In contrast, not all RT based measures were highly correlated. Additionally, our results revealed a speed-accuracy trade-off. Thus, accuracy and RT based measures provided conflicting conclusions regarding ANS acuity. Therefore, we investigated in two further experiments which type of measure (accuracy or RT) is more informative about the underlying ANS acuity, depending on participants' preferences for accuracy or speed. To this end, we manipulated participants' preferences for accuracy or speed both explicitly using different task instructions and implicitly varying presentation duration. Accuracy based measures were more informative about the underlying ANS acuity than RT based measures. Moreover, the influence of the underlying representations on accuracy data was more pronounced when participants preferred accuracy over speed after the accuracy instruction as well as for long or unlimited presentation durations. Implications regarding the diffusion model as a theoretical framework of dot comparison as well as regarding the relationship between ANS acuity and math performance are discussed.
Time for action versus action in time: time estimation differs between motor preparation and execution
2016-09-16

Theories relating to time perception and motor performance predict very different temporal distortions depending on the synchronisation or succession of temporal processing and motor behaviour. However, our knowledge about the temporal difference between motor preparation and execution is still scarce. In order to expand on prior studies, two different time reproduction tasks were utilised to measure motor preparation and motor execution. We found that motor preparation of a planned action allows participants to complete the time reproduction task more accurately and, in short duration trials, less variably than for motor execution. Furthermore, under-reproduction was found in motor preparation compared to motor execution, which may be caused by increased temporal information processing. According to the attentional gate theory, more attention allocated to time processing and reduced motor distraction leads to less temporal distortion in the motor preparation. The findings are also important for designing to study consciousness, temporal and visual processing.
Improved antireflection coated microspheres for biological applications of optical tweezers
2016-09-16

The success of optical tweezers in cellular biology<sup>1</sup> is in part due to the wide range of forces that can be applied, from femto- to hundreds of pico-Newtons; nevertheless extending the range of applicable forces to the nanoNewton regime opens access to a new set of phenomena that currently lie beyond optical manipulation. A successful approach to overcome the conventional limits on trapping forces involves the optimization of the trapped probes. Jannasch <i>et al.</i><sup>2</sup> demonstrated that an anti-reflective shell of nanoporous titanium dioxide (<i>aTiO<sub>2</sub></i>, <i>n<sub>shell</sub></i> = 1.75) on a core particle made out of titanium dioxide in the anatase phase (<i>cTiO<sub>2</sub></i>, <i>n<sub>core</sub> </i>= 2.3) results in trappable microspheres capable to reach forces above 1 nN. Here we present how the technique can be further improved by coating the high refractive index microspheres with an additional anti-reflective shell made out of silica (<i>SiO<sub>2</sub></i>). This external shell not only improves the trap stability for microspheres of different sizes, but also enables the use of functionalization techniques already established for commercial silica beads in biological experiments. We are also investigating the use of these new microspheres as probes to measure adhesion forces between intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) in effector T-Cells and will present preliminary results comparing standard and high-index beads.
Empathy for pain influences perceptual and motor processing: Evidence from response force, ERPs, and EEG oscillations
2016-09-17

In the present study we investigated the nature and chronometry of empathy for pain influences on perceptual and motor processes. Thus, event-related brain potentials (ERPs), response force (RF) and oscillatory electroencephalography (EEG) activity were measured while participants were presented with pictures of body parts in painful or neutral situations. Their task consisted in either judging the painfulness of the stimuli or counting the body parts displayed. ERP results supported the assumption of an early automatic component of empathy for pain, as reflected by the early posterior negativity (EPN), and of a late controlled component, as reflected by the late posterior positivity (P3). RF indicated that empathy-evoking stimuli facilitate motor responses if attention is directed toward the pain dimension, whereas EEG oscillations in the mu-and beta-band revealed, independent of the task, an enhanced activation of the sensorimotor cortex after the response to painful compared to neutral stimuli. In conclusion, present findings indicate that empathy-evoking stimuli produce automatic and controlled effects on both perceptual and motor processing.
Peeking under the Iron Curtain: Development of a Microcosm for Imaging the Colonization of Steel Surfaces by Mariprofundus sp. Strain DIS-1, an Oxygen-Tolerant Fe-Oxidizing Bacterium
2016-09-17

ABSTRACT Microbially influenced corrosion (MIC) is a major cause of damage to steel infrastructure in the marine environment. Despite their ability to grow directly on Fe(II) released from steel, comparatively little is known about the role played by neutrophilic iron-oxidizing bacteria (FeOB). Recent work has shown that FeOB grow readily on mild steel (1018 MS) incubated in situ or as a substrate for pure cultures in vitro ; however, details of how they colonize steel surfaces are unknown yet are important for understanding their effects. In this study, we combine a novel continuously upwelling microcosm with confocal laser scanning microscopy (CLSM) to determine the degree of colonization of 1018 MS by the marine FeOB strain DIS-1. 1018 MS coupons were incubated with sterile seawater (pH 8) inoculated with strain DIS-1. Incubations were performed both under oxic conditions and in an anoxic-to-oxic gradient. Following incubations of 1 to 10 days, the slides were removed from the microcosms and stained to visualize both cells and stalk structures. Stained coupons were visualized by CLSM after being mounted in a custom frame to preserve the three-dimensional structure of the biofilm. The incubation of 1018 MS coupons with strain DIS-1 under oxic conditions resulted in initial attachment of cells within 2 days and nearly total coverage of the coupon with an ochre film within 5 days. CLSM imaging revealed a nonadherent biofilm composed primarily of the Fe-oxide stalks characteristic of strain DIS-1. When incubated with elevated concentrations of Fe(II), DIS-1 colonization of 1018 MS was inhibited. IMPORTANCE These experiments describe the growth of a marine FeOB in a continuous culture system and represent direct visualizations of steel colonization by FeOB. We anticipate that these experiments will lay the groundwork for studying the mechanisms by which FeOB colonize steel and help to elucidate the role played by marine FeOB in MIC. These observations of the interaction between an FeOB, strain DIS-1, and steel suggest that this experimental system will provide a useful model for studying the interactions between microbes and solid substrates.
Profiles of miRNAs matched to biology in aromatase inhibitor resistant breast cancer
2016-09-17

Aromatase inhibitor (AI) resistance during breast cancer treatment is mimicked by MCF-7:5C (5C) and MCF-7:2A (2A) cell lines that grow spontaneously. Survival signaling is reconfigured but cells are vulnerable to estradiol (E2)-inducible apoptosis. These model systems have alterations of stress related pathways including the accumulation of endoplasmic reticulum, oxidative, and inflammatory stress that occur prior to E2-induced apoptosis. We investigated miRNA expression profiles of 5C and 2A to characterize their AI resistance phenotypes. Affymetrix GeneChip miRNA2.0 arrays identified 184 miRNAs differentially expressed in 2A and 5C compared to E2-free wild-type MCF-7:WS8. In 5C, 34 miRNAs of the DLK1-DIO3 locus and miR-31 were overexpressed, whereas miR-222 was low. TCGA data revealed poor and favorable overall survival for low miR-31 and miR-222 levels, respectively (HR=3.0, 95% CI:1.9-4.8; HR=0.3, 95% CI:0.1-0.6). Targets of deregulated miRNAs were identified using CLIP-confirmed TargetScan predictions. KEGG enrichment analyses for 5C- and 2A-specific target gene sets revealed pathways associated with cell proliferation including insulin, mTOR, and ErbB signaling as well as immune response and metabolism. Key genes overrepresented in 5C- and 2A-specific pathway interaction networks including EGFR, IGF1R and PIK3R1 had lower protein levels in 5C compared to 2A and were found to be differentially modulated by respective miRNA sets. Distinct up-regulated miRNAs from the DLK1-DIO3 locus may cause these attenuative effects as they are predicted to interact with corresponding 3' untranslated regions. These new miRNA profiles become an important regulatory database to explore E2-induced apoptotic mechanisms of clinical relevance for the treatment of resistant breast cancer.
Managing Incidental Lung Nodules in Patients With a History of Oncologic Disease
2016-09-17

Purpose: The aim of this study was to analyze the impact that a clinical history of an oncologic disease may have on the management decisions for incidentally detected lung nodules on chest computed tomographic (CT) examinations. Materials and Methods: An electronic survey was sent to all 796 members of the Society of Thoracic Radiology regarding criteria for the management of incidentally detected lung nodules in oncologic patients, as well as recommendations for nodule follow-up. Nodule characteristics and clinical parameters used by respondents were analyzed. Differences between variables were examined using the χ 2 test. Results: Of the 796 Society of Thoracic Radiology members, 178 (22.36%) replied. Most respondents were subspecialized in cardiothoracic imaging (92.70%) and practiced in an “academic or teaching hospital setting” (75.28%) with a “dedicated oncology center” (94.03%). “History of oncologic disease” was the most important factor (98.87%) for management decisions. In patients with such a history, respondents most commonly used “experience and common sense” (56.74%) and reported “all incidentally found lung nodules” (65.73%, P &lt;0.0001). “Size” and “shape” were the 2 most important nodule characteristics (33.61% and 27.05%, respectively) used to consider a nodule “clinically relevant,” and “size” (44.07%) was also the most important nodule characteristic prompting recommendation for short-term CT follow-up. Follow-up CT examinations in oncologic patients were recommended by 75.84% of respondents. Conclusions: In patients with a history of oncologic disease, radiologists tend to report every detected nodule and to routinely recommend follow-up CT examinations. Although most radiologists rely on “experience and common sense” in managing these nodules, greater standardization of lung nodule management in oncologic patients is needed, ideally through guidelines tailored to this patient population.
Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans
2016-09-20

These data provide novel insight to the organo-specific release/uptake of acylcarnitines. The liver is a major contributor to systemic short chain acylcarnitines, whereas the muscle tissue releases mostly medium chain acylcarnitines during exercise, indicating that other tissues are contributing to the systemic increase in long chain acylcarnitines.