julilili42/papers huggingface dataset:
PLAC8 Localizes to the Inner Plasma Membrane of Pancreatic Cancer Cells and Regulates Cell Growth and Disease Progression through Critical Cell-Cycle Regulatory Pathways
2015-12-16

Abstract Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumors and is generally strongly resistant to currently available chemo- and/or radiotherapy regimens, including targeted molecular therapies. Therefore, unraveling the molecular mechanisms underlying the aggressive behavior of pancreatic cancer is a necessary prerequisite for the development of novel therapeutic approaches. We previously identified the protein placenta-specific 8 (PLAC8, onzin) in a genome-wide search for target genes associated with pancreatic tumor progression and demonstrated that PLAC8 is strongly ectopically expressed in advanced preneoplastic lesions and invasive human PDAC. However, the molecular function of PLAC8 remained unclear, and accumulating evidence suggested its role is highly dependent on cellular and physiologic context. Here, we demonstrate that in contrast to other cellular systems, PLAC8 protein localizes to the inner face of the plasma membrane in pancreatic cancer cells, where it interacts with specific membranous structures in a temporally and spatially stable manner. Inhibition of PLAC8 expression strongly inhibited pancreatic cancer cell growth by attenuating cell-cycle progression, which was associated with transcriptional and/or posttranslational modification of the central cell-cycle regulators CDKN1A, retinoblastoma protein, and cyclin D1 (CCND1), but did not impact autophagy. Moreover, Plac8 deficiency significantly inhibited tumor formation in genetically engineered mouse models of pancreatic cancer. Together, our findings establish PLAC8 as a central mediator of tumor progression in PDAC and as a promising candidate gene for diagnostic and therapeutic targeting. Cancer Res; 76(1); 96–107. ©2015 AACR.
Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells
2015-12-16

The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2), transgelin (TAGLN), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC; MYH11) according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion channel activity comparable to bladder SMCs which may be important for urological regenerative medicine applications.
The two faces of the inflammasome adaptor ASC in epithelial skin carcinogenesis.
2015-12-16

The development of tumours is a multistep process during which cells acquire the capability to sustain proliferation, evade growth suppressors and/or resist cell death. One factor, which is increasingly recognised to influence tumour progression, is the inflammatory environment of the tumour. The responsible molecular mechanisms and signalling pathways are only beginning to emerge. One major pathway able to induce potent inflammation is the activation of the inflammasome and the subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Both these cytokines have been implicated in tumour-genesis/progression. However, evidence for the role of inflammasomes in this process is still scarce and mainly derived from murine colitis associated tumour models. In this short review we discuss current knowledge on the role of inflammasomes in epithelial cancer of the gut and skin with a special focus on the complex role of the inflammasome adaptor ASC in epithelial skin carcinogenesis.
Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation
2015-12-17

Objective Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination—known as infantile convulsions and paroxysmal choreoathetosis (ICCA)—are related autosomal dominant diseases. PRRT2 (proline‐rich transmembrane protein 2 gene) has been identified as the major gene in all 3 conditions, found to be mutated in 80 to 90% of familial and 30 to 35% of sporadic cases. Methods We searched for the genetic defect in PRRT2 ‐negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed cliniconeurophysiological workup. Results In 3 families with a total of 16 affected members, we identified the same, cosegregating heterozygous missense mutation (c.4447G&gt;A; p.E1483K) in SCN8A , encoding a voltage‐gated sodium channel. A founder effect was excluded by linkage analysis. All individuals except 1 had normal cognitive and motor milestones, neuroimaging, and interictal neurological status. Fifteen affected members presented with afebrile focal or generalized tonic–clonic seizures during the first to second year of life; 5 of them experienced single unprovoked seizures later on. One patient had seizures only at school age. All patients stayed otherwise seizure‐free, most without medication. Interictal electroencephalogram (EEG) was normal in all cases but 2. Five of 16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or “shivering” attacks, triggered by stretching, motor initiation, or emotional stimuli. In 1 case, we recorded typical PKD spells by video‐EEG‐polygraphy, documenting a cortical involvement. Interpretation Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical–genetic spectrum of combined epileptic and dyskinetic syndromes. ANN NEUROL 2016;79:428–436
MASP-1 and MASP-2 Do Not Activate Pro–Factor D in Resting Human Blood, whereas MASP-3 Is a Potential Activator: Kinetic Analysis Involving Specific MASP-1 and MASP-2 Inhibitors
2015-12-17

Abstract It had been thought that complement factor D (FD) is activated at the site of synthesis, and only FD lacking a propeptide is present in blood. The serum of mannose-binding lectin–associated serine protease (MASP)-1/3(−/−) mice contains pro-FD and has markedly reduced alternative pathway activity. It was suggested that MASP-1 and MASP-3 directly activate pro-FD; however, other experiments contradicted this view. We decided to clarify the involvement of MASPs in pro-FD activation in normal, as opposed to deficient, human plasma and serum. Human pro-FD containing an APPRGR propeptide was produced in insect cells. We measured its activation kinetics using purified active MASP-1, MASP-2, MASP-3, as well as thrombin. We found all these enzymes to be efficient activators, whereas MASP proenzymes lacked such activity. Pro-FD cleavage in serum or plasma was quantified by a novel assay using fluorescently labeled pro-FD. Labeled pro-FD was processed with t1/2s of ∼3 and 5 h in serum and plasma, respectively, showing that proteolytic activity capable of activating pro-FD exists in blood even in the absence of active coagulation enzymes. Our previously developed selective MASP-1 and MASP-2 inhibitors did not reduce pro-FD activation at reasonable concentration. In contrast, at very high concentration, the MASP-2 inhibitor, which is also a poor MASP-3 inhibitor, slowed down the activation. When recombinant MASPs were added to plasma, only MASP-3 could reduce the half-life of pro-FD. Combining our quantitative data, MASP-1 and MASP-2 can be ruled out as direct pro-FD activators in resting blood; however, active MASP-3 is a very likely physiological activator.
Peptidoglycan Perception in Plants
2015-12-17

Higher eukaryotes have evolved mechanisms to detect and discriminate between a wide range of commensal and infectious microorganisms. The first inducible line of defence common between plant and animal systems is microbe-associated molecular pattern (MAMP)-triggered immunity (MTI) [1,2]. MTI is based on the recognition of certain structurally highly conserved and, for the microbe, indispensable patterns that are usually not present in the attacked host organism. In plants, these MAMPs are detected at the cell surface by pattern recognition receptors (PRRs) [3,4]. Results from recent years indicate that PRRs are part of larger protein complexes, most of which associate only in the presence of the respective MAMP [5]. Subsequently, host defences are mobilised, eventually leading to a limitation of pathogen spreading and multiplication.
Clear differences in metabolic and morphological adaptations of akinetes of two Nostocales living in different habitats
2015-12-17

Akinetes are resting spore-like cells formed by some heterocyst-forming filamentous cyanobacteria for surviving long periods of unfavourable conditions. We studied the development of akinetes in two model strains of cyanobacterial cell differentiation, the planktonic freshwater Anabaena variabilis ATCC 29413 and the terrestrial or symbiotic Nostoc punctiforme ATCC 29133, in response to low light and phosphate starvation. The best trigger of akinete differentiation of Anabaena variabilis was low light; that of N. punctiforme was phosphate starvation. Light and electron microscopy revealed that akinetes of both species differed from vegetative cells by their larger size, different cell morphology and large number of intracellular granules. Anabaena variabilis akinetes had a multilayer envelope; those of N. punctiforme had a simpler envelope. During akinete development of Anabaena variabilis, the amount of the storage compounds cyanophycin and glycogen increased transiently, whereas in N. punctiforme, cyanophycin and lipid droplets increased transiently. Photosynthesis and respiration decreased during akinete differentiation in both species, and remained at a low level in mature akinetes. The clear differences in the metabolic and morphological adaptations of akinetes of the two species could be related to their different lifestyles. The results pave the way for genetic and functional studies of akinete differentiation in these species.
Evidence for Enhanced Interoceptive Accuracy in Professional Musicians
2015-12-17

Interoception is defined as the perceptual activity involved in the processing of internal bodily signals. While the ability of internal perception is considered a relatively stable trait, recent data suggest that learning to integrate multisensory information can modulate it. Making music is a uniquely rich multisensory experience that has shown to alter motor, sensory, and multimodal representations in the brain of musicians. We hypothesize that musical training also heightens interoceptive accuracy comparable to other perceptual modalities. Thirteen professional singers, twelve string players, and thirteen matched non-musicians were examined using a well-established heartbeat discrimination paradigm complemented by self-reported dispositional traits. Results revealed that both groups of musicians displayed higher interoceptive accuracy than non-musicians, whereas no differences were found between singers and string-players. Regression analyses showed that accumulated musical practice explained about 49% variation in heartbeat perception accuracy in singers but not in string-players. Psychometric data yielded a number of psychologically plausible inter-correlations in musicians related to performance anxiety. However, dispositional traits were not a confounding factor on heartbeat discrimination accuracy. Together, these data provide first evidence indicating that professional musicians show enhanced interoceptive accuracy compared to non-musicians. We argue that musical training largely accounted for this effect.
Processing grammatical evidentiality and time reference in Turkish heritage and monolingual speakers
2015-12-18

In the current study, we examined how adult heritage and monolingual speakers of Turkish process evidentiality (the linguistic expression of information source) through finite verb inflections and time reference, expressed on non-finite participles. A sentence-verification task was used to measure participants’ sensitivity to evidentiality and time-reference violations in Turkish. Our findings showed that the heritage speakers were less accurate and slower than the monolinguals in responding to both evidentiality and time-reference violations. Also, the heritage speakers made more errors and had longer RTs when responding to evidentiality violations as compared to time-reference violations. The monolinguals had longer RTs (and more accurate responses) to time reference than to evidentiality violations. This study shows that evidentiality is susceptible to incomplete acquisition in Turkish heritage speakers. It is suggested that the requirement for simultaneous processing at different linguistic levels makes the evidentiality markers vulnerable.
Cylindrofridins A–C, Linear Cylindrocyclophane-Related Alkylresorcinols from the Cyanobacterium Cylindrospermum stagnale
2015-12-18

A rapid and exhaustive one-step biomass extraction as well as an enrichment and cleanup procedure has been developed for HPLC-UV detection and quantification of closely related [7.7]paracyclophanes and structural derivatives based on a two-phase solvent system. The procedure has been validated using the biomass of the carbamidocyclophane- and cylindrocyclophane-producing cyanobacterium Nostoc sp. CAVN2 and was utilized to perform a screening comprising 102 cyanobacterial strains. As a result, three new cylindrocyclophane-related alkylresorcinols, cylindrofridins A-C (1-3), and known cylindrocyclophanes (4-6) were detected and isolated from Cylindrospermum stagnale PCC 7417. Structures of 1-3 were elucidated by a combination of 1D and 2D NMR experiments, HRMS, and ECD spectroscopy. Cylindrofridin A (1) is the first naturally occurring [7.7]paracyclophane-related monomeric derivative. In contrast, cylindrofridins B (2) and C (3) represent dimers related to 1. Due to chlorination at the alkyl carbon atom in 1-3, the site of [7.7]paracyclophane macrocycle formation, the cylindrofridins represent linearized congeners of the cylindrocyclophanes. Compounds 1-3 were not toxic against nontumorigenic HaCaT cells (IC50 values >25 μM) compared to the respective cylindrocyclophanes, but 1 was the only cylindrofridin showing moderate activity against methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae with MIC values of 9 and 17 μM, respectively.
Emotional Distraction and Bodily Reaction: Modulation of Autonomous Responses by Anodal tDCS to the Prefrontal Cortex
2015-12-18

Prefrontal electric stimulation has been demonstrated to effectively modulate cognitive processing. Specifically, the amelioration of cognitive control (CC) over emotional distraction by transcranial direct current stimulation (tDCS) points toward targeted therapeutic applications in various psychiatric disorders. In addition to behavioral measures, autonomous nervous system (ANS) responses are fundamental bodily signatures of emotional information processing. However, interactions between the modulation of CC by tDCS and ANS responses have received limited attention. We here report on ANS data gathered in healthy subjects that performed an emotional CC task parallel to the modulation of left prefrontal cortical activity by 1 mA anodal or sham tDCS. Skin conductance responses (SCRs) to negative and neutral pictures of human scenes were reduced by anodal as compared to sham tDCS. Individual SCR amplitude variations were associated with the amount of distraction. Moreover, the stimulation-driven performance- and SCR-modulations were related in form of a quadratic, inverse-U function. Thus, our results indicate that non-invasive brain stimulation (i.e., anodal tDCS) can modulate autonomous responses synchronous to behavioral improvements, but the range of possible concurrent improvements from prefrontal stimulation is limited. Interactions between cognitive, affective, neurophysiological, and vegetative responses to emotional content can shape brain stimulation effectiveness and require theory-driven integration in potential treatment protocols.
HH 1158: THE LOWEST LUMINOSITY EXTERNALLY IRRADIATED HERBIG–HARO JET
2015-12-18

We have identified a new externally irradiated Herbig-Haro (HH) jet, HH 1158,\\nwithin ~2 pc of the massive OB type stars in the sigma Orionis cluster. At an\\nLbol ~ 0.1 Lsun, HH 1158 is the lowest luminosity irradiated HH jet identified\\nto date in any cluster. Results from the analysis of high-resolution optical\\nspectra indicate asymmetries in the brightness, morphology, electron density,\\nvelocity, and the mass outflow rates for the blue and red-shifted lobes. We\\nconstrain the position angle of the HH 1158 jet at 102+/-5 degree. The mass\\noutflow rate and the mean accretion rate for HH 1158 using multiple diagnostics\\nare estimated to be (5.2 +/- 2.6) x 10^(-10) Msun/yr and (3.0 +/- 1.0) x\\n10^(-10) Msun/yr, respectively. The properties for HH 1158 are notably similar\\nto the externally irradiated HH 444 -- HH 447 jets previously identified in\\nsigma Orionis. In particular, the morphology is such that the weaker jet beam\\nis tilted towards the massive stars, indicating a higher extent of\\nphoto-evaporation. The high value for the Halpha/[SII] ratio is also consistent\\nwith the ratios measured in other irradiated jets, including HH 444 -- HH 447.\\nThe presence of an extended collimated jet that is bipolar and the evidence of\\nshocked emission knots make HH 1158 the first unique case of irradiated HH jets\\nat the very low-luminosity end, and provides an opportunity to learn the\\nphysical properties of very faint HH jet sources.\\n
Coexistence of Microaerophilic, Nitrate-Reducing, and Phototrophic Fe(II) Oxidizers and Fe(III) Reducers in Coastal Marine Sediment
2015-12-19

ABSTRACT Iron is abundant in sediments, where it can be biogeochemically cycled between its divalent and trivalent redox states. The neutrophilic microbiological Fe cycle involves Fe(III)-reducing and three different physiological groups of Fe(II)-oxidizing microorganisms, i.e., microaerophilic, anoxygenic phototrophic, and nitrate-reducing Fe(II) oxidizers. However, it is unknown whether all three groups coexist in one habitat and how they are spatially distributed in relation to gradients of O 2 , light, nitrate, and Fe(II). We examined two coastal marine sediments in Aarhus Bay, Denmark, by cultivation and most probable number (MPN) studies for Fe(II) oxidizers and Fe(III) reducers and by quantitative-PCR (qPCR) assays for microaerophilic Fe(II) oxidizers. Our results demonstrate the coexistence of all three metabolic types of Fe(II) oxidizers and Fe(III) reducers. In qPCR, microaerophilic Fe(II) oxidizers ( Zetaproteobacteria ) were present with up to 3.2 × 10 6 cells g dry sediment −1 . In MPNs, nitrate-reducing Fe(II) oxidizers, anoxygenic phototrophic Fe(II) oxidizers, and Fe(III) reducers reached cell numbers of up to 3.5 × 10 4 , 3.1 × 10 2 , and 4.4 × 10 4 g dry sediment −1 , respectively. O 2 and light penetrated only a few millimeters, but the depth distribution of the different iron metabolizers did not correlate with the profile of O 2 , Fe(II), or light. Instead, abundances were homogeneous within the upper 3 cm of the sediment, probably due to wave-induced sediment reworking and bioturbation. In microaerophilic Fe(II)-oxidizing enrichment cultures, strains belonging to the Zetaproteobacteria were identified. Photoferrotrophic enrichments contained strains related to Chlorobium and Rhodobacter ; the nitrate-reducing Fe(II) enrichments contained strains related to Hoeflea and Denitromonas . This study shows the coexistence of all three types of Fe(II) oxidizers in two near-shore marine environments and the potential for competition and interrelationships between them.
Peripheral Blood Monocytes as Adult Stem Cells: Molecular Characterization and Improvements in Culture Conditions to Enhance Stem Cell Features and Proliferative Potential
2015-12-20

Adult stem or programmable cells hold great promise in diseases in which damaged or nonfunctional cells need to be replaced. We have recently demonstrated that peripheral blood monocytes can be differentiated in vitro into cells resembling specialized cell types like hepatocytes and pancreatic beta cells. During phenotypic conversion, the monocytes downregulate monocyte/macrophage differentiation markers, being indicative of partial dedifferentiation, and are partially reprogrammed to acquire a state of plasticity along with expression of various markers of pluripotency and resumption of mitosis. Upregulation of stem cell markers and mitotic activity in the cultures was shown to be controlled by autocrine production/secretion of activin A and transforming growth factor‐beta (TGF‐ β ). These reprogrammed monocyte derivatives were termed “programmable cells of monocytic origin” (PCMO). Current efforts focus on establishing culture conditions that increase both the plasticity and proliferation potential of PCMO in order to be able to generate large amounts of blood‐derived cells suitable for both autologous and allogeneic therapies.
Learning and Cognitive Maturation
2015-12-20

Healthy aging is associated with cognitive changes that are commonly thought to reflect diminished processing power in our minds and brains. Formally, however, in the absence of functional models of cognitive processing and without controlling for the way that learning tends to result in increases in the amount of information processed by the cognitive system, it is impossible to establish whether cognitive processing capacities actually do decline over the lifespan. When the cognitive processes measured by psychometric tests of behavior are formally defined, the performance of older adults can be seen to show little evidence of decline; rather, changes in test scores closely reflect the predictable performance of a system with consistent capacity‐processing increasing information loads as age and experience increase.