julilili42/papers huggingface dataset:
Development and Function of the Voltage-Gated Sodium Current in Immature Mammalian Cochlear Inner Hair Cells
2012-09-19

Inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea, fire spontaneous Ca(2+) action potentials before the onset of hearing. Although this firing activity is mainly sustained by a depolarizing L-type (Ca(V)1.3) Ca(2+) current (I(Ca)), IHCs also transiently express a large Na(+) current (I(Na)). We aimed to investigate the specific contribution of I(Na) to the action potentials, the nature of the channels carrying the current and whether the biophysical properties of I(Na) differ between low- and high-frequency IHCs. We show that I(Na) is highly temperature-dependent and activates at around -60 mV, close to the action potential threshold. Its size was larger in apical than in basal IHCs and between 5% and 20% should be available at around the resting membrane potential (-55 mV/-60 mV). However, in vivo the availability of I(Na) could potentially increase to >60% during inhibitory postsynaptic potential activity, which transiently hyperpolarize IHCs down to as far as -70 mV. When IHCs were held at -60 mV and I(Na) elicited using a simulated action potential as a voltage command, we found that I(Na) contributed to the subthreshold depolarization and upstroke of an action potential. We also found that I(Na) is likely to be carried by the TTX-sensitive channel subunits Na(V)1.1 and Na(V)1.6 in both apical and basal IHCs. The results provide insight into how the biophysical properties of I(Na) in mammalian cochlear IHCs could contribute to the spontaneous physiological activity during cochlear maturation in vivo.
Long-term meteorological and hydrological dryness and wetness conditions in the Zhujiang River Basin, South China
2012-09-19

Abstract. Floods and droughts are frequently causing large economic losses in China. These conditions vary in space, time, and magnitude. In this study, long-term meteorological and hydrological dryness and wetness conditions are analyzed for the Xijiang River Basin which is the largest tributary of the Zhujiang (Pearl) River. A very similar inter-annual course of precipitation and discharge can be observed. The standardized precipitation index (SPI) is used to show dryness and wetness pattern in the six sub-basins of the Xijiang River. The SPI-24 correlates high with the standardized discharge index (SDI-24) for Gaoyao hydrological station at the mouth of Xijiang River. Distinct long-term dryness and wetness sequences are found in the time series for the SPI-24 and SDI-24. The principal component analysis reveals many spatial interdependencies in dryness and wetness conditions for the sub-basins and explains some spatio-temporal disparities. Moderate dryness conditions have a larger spatial impact than moderate wetness conditions in the sub-basins. The loading pattern of the first principal component shows that the correlation with the entire Xijiang River Basin is highest in the eastern and lowest in the western sub-basins. Further spatial dipole conditions explain the spatio-temporal heterogeneity of dryness and wetness conditions. Accordingly, the precipitation in the eastern sub-basins contributes more to the hydrological wetness conditions than in the western sub-basins, which mainly contribute to dryness patterns. The spectral analysis for the SPI-24 (entire Xijiang River Basin) and SDI-24 shows similar peaks for periods of 11–14.7 yr, 2.8 yr, 3.4–3.7 yr, and 6.3–7.3 yr. The same periods can be found for the SPI-24 of Xijiang River's six sub-basins with some variability in the magnitude. The wavelet analysis shows that the most significant periods are stable over time since the 1980s. The extrapolations of the reconstructed time series do not suggest any spatial or temporal changes in the occurrence of dryness and wetness conditions in the next two decades but a continuation of the observed cycles at given magnitude. It can be concluded that long-term hydrological dryness and wetness conditions are directly caused by periodic cycles of meteorological conditions (i.e. precipitation). The applied methodologies prove to be able to identify spatial interdependencies and corresponding regional disparities, and to detect significant periodicities in long-term dryness and wetness conditions in the Xijiang River Basin.
The Archaeal Proteasome Is Regulated by a Network of AAA ATPases
2012-09-20

The proteasome is the central machinery for targeted protein degradation in archaea, Actinobacteria, and eukaryotes. In its basic form, it consists of a regulatory ATPase complex and a proteolytic core particle. The interaction between the two is governed by an HbYX motif (where Hb is a hydrophobic residue, Y is tyrosine, and X is any amino acid) at the C terminus of the ATPase subunits, which stimulates gate opening of the proteasomal α-subunits. In archaea, the proteasome-interacting motif is not only found in canonical proteasome-activating nucleotidases of the PAN/ARC/Rpt group, which are absent in major archaeal lineages, but also in proteins of the CDC48/p97/VAT and AMA groups, suggesting a regulatory network of proteasomal ATPases. Indeed, Thermoplasma acidophilum, which lacks PAN, encodes one CDC48 protein that interacts with the 20S proteasome and activates the degradation of model substrates. In contrast, Methanosarcina mazei contains seven AAA proteins, five of which, both PAN proteins, two out of three CDC48 proteins, and the AMA protein, function as proteasomal gatekeepers. The prevalent presence of multiple, distinct proteasomal ATPases in archaea thus results in a network of regulatory ATPases that may widen the substrate spectrum of proteasomal protein degradation.
Modified Acidic Nonsteroidal Anti-Inflammatory Drugs as Dual Inhibitors of mPGES-1 and 5-LOX
2012-09-20

mPGES-1 is a promising target for development of new anti-inflammatory drugs. We aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs by replacing the carboxylic acid functionality by sulfonamide moieties. Compounds were also tested for 5-LOX inhibition. The most potent mPGES-1 inhibitor was lonazolac derivative 22 (IC50 = 0.16 μM), while the best 5-LOX inhibition was attained by indomethacin derivative 17 (IC50 = 0.9 μM). Inhibition of COX-1 activity was completely removed.
Localization of a Subset of Yeast mRNAs Depends on Inheritance of Endoplasmic Reticulum
2012-09-20

Localization of messenger RNA ( mRNAs ) contributes to generation and maintenance of cellular asymmetry, embryonic development and neuronal function. The She1‐3 protein machinery in Saccharomyces cerevisiae localizes &gt;30 mRNAs to the bud tip, including 13 mRNAs encoding membrane or secreted proteins. Ribonucleoprotein ( RNP ) particles can co‐localize with tubular endoplasmic reticulum ( ER ) structures that form the initial elements for segregation of cortical ER ( cER ), suggesting a coordination of mRNA localization and cER distribution. By investigating localization of MS2 ‐tagged mRNAs in yeast defective at various stages of cER segregation, we demonstrate that proper cER segregation is required for localization of only a subset of mRNAs . These mRNAs include WSC2 , IST2 , EAR1 and SRL1 that encode membrane or ER associated proteins and are expressed during S and G2 phases of the cell cycle when tubular ER movement into the bud occurs. Translation of WSC2 is not required for localization, ruling out co‐translational targeting of this mRNA . Localization of ASH1 mRNA is independent of cER segregation, which is consistent with the expression pattern of ASH1 at late mitosis. Our findings indicate the presence of two different pathways to localize mRNAs to the yeast bud.
Human gastric TFF2 peptide contains an N-linked fucosylated N,N'-diacetyllactosediamine (LacdiNAc) oligosaccharide
2012-09-20

In the human stomach, the peptide trefoil factor family 2 (TFF2) is secreted together with the mucin MUC6 by mucous neck cells (MNCs) and antral gland cells. TFF2 is strongly associated with the gastric mucus and promotes gastric restitution. Here, TFF2 was purified from the human corpus and antrum, respectively, by size-exclusion chromatography, and the N-linked glycan structure at N-15 of the mature peptide was determined. As a hallmark, the unusual monofucosylated N,N'-diacetylhexosediamine (tentatively assigned as GalNAcβ1 → 4GlcNAc, LacdiNAc) modification was detected as the terminal structure of a bi-antennary complex type N-glycan exhibiting also core fucosylation. Replicate analyses did not show microheterogeneities in the fraction of peptide-N-glycosidase F cleaved and permethylated N-glycans when analyzed by matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS). On the glycopeptide level, a minor glycan microheterogeneity was evident in liquid chromatography-electrospray ionization (ESI)-MS, demonstrating the presence of underfucosylated species. The tryptic TFF2 N-glycopeptide p34-39 (LSPHNR N-glycosylated with Fuc3Hex3HexNAc6) was identified by both ESI-tandem mass spectrometry and MALDI-post-source decay analysis. Lectin analyses with the Wisteria floribunda agglutinin indicated the potential presence of LacdiNAc terminating glycans and revealed minor differences between TFF2 from fundic units, i.e. MNCs, and antral units, i.e. antral gland cells. Strikingly, on the level of the primary structure, there was no indication that the formation of the proposed LacdiNAc structure is cis-controlled by a peptidic determinant related to the published sequences.
Two-Dimensional Peptide Separation Improving Sensitivity of Selected Reaction Monitoring-Based Quantitative Proteomics in Mouse Liver Tissue: Comparing Off-Gel Electrophoresis and Strong Cation Exchange Chromatography
2012-09-20

Protein expression analysis is one of the most powerful tools to further the understanding of biological systems. Progress in the field of mass spectrometry has shifted focus from gel-based approaches to the upcoming LC-selected reaction monitoring (SRM) technique which combines high technical accuracy with absolute quantification of proteins and the capability for high-throughput analyses. Due to these properties, LC-SRM has the potential to become the foundation for biomarker analysis, targeted hypothesis driven proteomic studies and contribute to the field of systems biology. While the performance of LC-SRM applied to samples from various bodily fluids, particularly plasma, and microorganisms has been extensively investigated, there is only little experience with its application to animal tissue samples. Here, we show that a conventional one-dimensional LC-SRM workflow applied to mouse liver tissue suffers from a shortcoming in terms of sensitivity for lower abundance proteins. This problem could be solved through the extension of the standard workflow by an additional dimension of separation at the peptide level prior to online LC-SRM. For this purpose, we used off-gel electrophoresis (OGE) which is also shown to outperform strong cation exchange (SCX) in terms of resolution, gain of signal intensity, and predictability of separation. The extension of the SRM workflow by a high resolving peptide separation technique is an ideal combination as it allows the addition of stable isotope standards directly after trytic digestion and will increase the dynamic range of protein abundances amenable by SRM in animal tissue.
Gene Flow among Populations of Two Rare Co-Occurring Fern Species Differing in Ploidy Level
2012-09-20

Differences in ploidy levels among different fern species have a vast influence on their mating system, their colonization ability and on the gene flow among populations. Differences in the colonization abilities of species with different ploidy levels are well known: tetraploids, in contrast to diploids, are able to undergo intra-gametophytic selfing. Because fertilization is a post-dispersal process in ferns, selfing results in better colonization abilities in tetraploids because of single spore colonization. Considerably less is known about the gene flow among populations of different ploidy levels. The present study examines two rare fern species that differ in ploidy. While it has already been confirmed that tetraploid species are better at colonizing, the present study focuses on the gene flow among existing populations. We analyzed the genetic structure of a set of populations in a 10×10 km study region using isoenzymes. Genetic variation in tetraploid species is distributed mainly among populations; the genetic distance between populations is correlated with the geographical distance, and larger populations host more genetic diversity than smaller populations. In the diploid species, most variability is partitioned within populations; the genetic distance is not related to geographic distance, and the genetic diversity of populations is not related to the population size. This suggests that in tetraploid species, which undergo selfing, gene flow is limited. In contrast, in the diploid species, which experience outcrossing, gene flow is extensive and the whole system behaves as one large population. Our results suggest that in ferns, the ability to colonize new habitats and the gene flow among existing populations are affected by the mating system.
The effectiveness of public sponsored training revisited: the importance of data and methodological choices
2012-09-20

As the first, substantive contribution, this paper revisits the effectiveness of two widely used public sponsored training programs, the first one focusing on intensive occupational training and the second one on short-term activation and job entry. We use an exceptionally rich administrative data set for Germany to estimate their employment and earnings effects in the early 2000s. We employ a stratified propensity score matching approach to address dynamic selection into heterogeneous programs. As a second, methodological contribution, we carefully assess to what extent various aspects of our empirical strategy such as conditioning flexibly on employment and benefit histories, the availability of rich personal information, handling of later program participations, and further methodological and specification choices affect estimation results. Our results imply pronounced negative lock-in effects in the short run in general and positive medium-run effects on employment and earnings when job-seekers enroll after having been unemployed for some time. We find that data and specification issues can have a large effect on impact estimates.
Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to mutations in the CRB1 gene
2012-09-21

In humans, the Crumbs homolog-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, we generated and analysed conditional knockout mice lacking CRB2 in the developing retina. Progressive disorganization was detected during late retinal development. Progressive thinning of the photoreceptor layer and sites of cellular mislocalization was detected throughout the CRB2-deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. Under scotopic conditions using electroretinography, the attenuation of the a-wave was relatively stronger than that of the b-wave, suggesting progressive degeneration of photoreceptors in adult animals. Histological analysis of newborn mice showed abnormal lamination of immature rod photoreceptors and disruption of adherens junctions between photoreceptors, Müller glia and progenitor cells. The number of late-born progenitor cells, rod photoreceptors and Müller glia cells was increased, concomitant with programmed cell death of rod photoreceptors. The data suggest an essential role for CRB2 in proper lamination of the photoreceptor layer and suppression of proliferation of late-born retinal progenitor cells.
Identification of the V600D mutation in Exon 15 of the BRAF oncogene in congenital, benign langerhans cell histiocytosis
2012-09-21

Abstract Langerhans cell histiocytosis (LCH) is a well‐known but rare disease that may occur at any age with markedly variable clinical features: self‐regressive, localized, multiorgan, aggressive, or fatal outcome. Congenital LCH is rare and often clinically benign. While LCH is characterized by a clonal proliferation of Langerhans cells, its etiology is unknown. Although BRAF V600E mutations were recently identified as a recurrent genetic alteration in LCH cases, the clinical significance of this mutation within the heterogeneous spectrum of LCH is also currently unknown. We studied a cutaneous, benign form of congenital LCH that occurred in a newborn male, without recurrence for 8 years. Histopathologically, the skin lesion excised after birth showed the typical cytologic and immunophenotypic features of LCH. Sequencing analysis of Exon 15 of the BRAF gene revealed the V600D mutation, with an allelic abundance of 25–30%, corresponding to the LCH cells being hemizygous for the mutant allele. BRAF V600E‐specific polymerase chain reaction was negative. Our report is the first to identify the rare, variant BRAF V600D mutation in LCH, and provides support for constitutively activated BRAF oncogene‐induced cell senescence as a mechanism of regression in congenital, benign LCH. Further, our clinicopathologic findings provide proof for the first time that the V600D mutation can also occur in the absence of ultraviolet light, and can occur in a clinically benign proliferation, similar to the V600E mutation. Additional clinicopathologic studies in larger numbers of LCH patients may be valuable to ascertain the pathophysiologic role of BRAF mutations in LCH. © 2012 Wiley Periodicals, Inc.
Identification of Successful Clinical fMRI Sessions in Children: An Objective Approach
2012-09-23

We demonstrate that an objective, automated framework for the classification of clinical pediatric fMRI sessions may provide important additional information, supporting visual evaluation, especially from sensorimotor and language perception domains. In the current form, atypical or strong network activation is not easily captured.
THE PHYSICS OF PROTOPLANETESIMAL DUST AGGLOMERATES. VII. THE LOW-VELOCITY COLLISION BEHAVIOR OF LARGE DUST AGGLOMERATES
2012-09-24

We performed micro-gravity collision experiments in our laboratory drop-tower using 5-cm-sized dust agglomerates with volume filling factors of 0.3 and 0.4, respectively. This work is an extension of our previous experiments reported in Beitz et al. (2011) to aggregates of more than one order of magnitude higher masses. The dust aggregates consisted of micrometer-sized silica particles and were macroscopically homogeneous. We measured the coefficient of restitution for collision velocities ranging from 1 cm/s to 0.5 m/s, and determined the fragmentation velocity. For low velocities, the coefficient of restitution decreases with increasing impact velocity, in contrast to findings by Beitz et al. (2011). At higher velocities, the value of the coefficient of restitution becomes constant, before the aggregates break at the onset of fragmentation. We interpret the qualitative change in the coefficient of restitution as the transition from a solid-body-dominated to a granular-medium-dominated behavior. We complement our experiments by molecular dynamics simulations of porous aggregates and obtain a reasonable match to the experimental data. We discuss the importance of our experiments for protoplanetary disks, debris disks, and planetary rings. The work is an extensional study to previous work of our group and gives a new insight in the velocity dependency of the coefficient of restitution due to improved measurements, better statistics and a theoretical approach.
Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone
2012-09-24

The combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead to an increased pCR rate in locally advanced rectal cancer. Patients with low-lying tumours especially may benefit when additional downsizing allows sphincter-preserving surgery.
The sulfur speciation in S-bearing minerals: New constraints by a combination of electron microprobe analysis and DFT calculations with special reference to sodalite-group minerals
2012-09-24

In this work, we present an improved method for the semi-quantitative determination of sulfur species in S-bearing minerals by electron microprobe analysis. For calibration, we analyzed several sulfate and sulfide standard minerals such as baryte, celestine, chalcopyrite, and pyrite, and correlated the results with theoretical calculations retrieved from density functional theory (DFT). We applied this method to natural sodalite-group minerals from various localities. In addition, we applied the more common Raman spectroscopy to some samples and show that this method cannot be applied to sodalite-group minerals to determine their sulfur speciation. We show that even though sodalite-group minerals have a complex crystal structure and are sensitive to the electron beam, electron microprobe analysis is a reliable tool for the analysis of their sulfur speciation. The natural sodalite-group minerals show systematic variations in sulfur speciation. These variations can be correlated with the independently determined oxidation state of the parental magmas thus making S-bearing sodalitegroup minerals good redox proxies, although we show that the electron microprobe analysis of the sulfur speciation is matrix-dependent, and the sulfur speciation itself depends on crystal chemistry and structure, and not only on fO2.
The reawakening of the sleeping X-ray pulsar XTE J1946+274
2012-09-24

We report on a series of outbursts of the high mass X-ray binary XTE\\nJ1946+274 in 2010/2011 as observed with INTEGRAL, RXTE, and Swift. We discuss\\npossible mechanisms resulting in the extraordinary outburst behavior of this\\nsource. The X-ray spectra can be described by standard phenomenological models,\\nenhanced by an absorption feature of unknown origin at about 10 keV and a\\nnarrow iron K alpha fluorescence line at 6.4 keV, which are variable in flux\\nand pulse phase. We find possible evidence for the presence of a cyclotron\\nresonance scattering feature at about 25 keV at the 93% level. The presence of\\na strong cyclotron line at 35 keV seen in data from the source's 1998 outburst\\nand confirmed by a reanalysis of these data can be excluded. This result\\nindicates that the cyclotron line feature in XTE J1946+274 is variable between\\nindividual outbursts.\\n
Ultrasonic monitoring of the effect of sodium hypochlorite on the elasticity of dentine
2012-09-25

Abstract Aim To determine the change in ultrasonic velocity of dentine after the application of 5% NaOCl. Methodology Twenty standardized plano‐parallel dentine bars were divided into two groups. Dentine bars were wetted on only one surface. The test group ( n = 10) was irrigated with 5% NaOCl, and the control group, ( n = 10) with saline. Ultrasonic velocities before and after irrigation were compared to determine the change in the modulus of elasticity. Finally, dentine bars were loaded until failure in a 3‐point bending test. Paired t ‐test and the mean of differences were used to assess the statistical significance between the groups. Results The mean ultrasonic velocity decreased by 1.4% after the application of NaOCl; no change was observed for saline. The mean velocity reduction of 49 m s −1 was found to be highly significant ( P = 0.004). The ultrasonically derived modulus of elasticity decreased by 2.6% compared to the initial value of 17.8 GPa. However, the observed reduction in elasticity derived from the 3‐point bending test was not significant ( P = 0.238). Conclusions NaOCl reduced the ultrasonic velocity of dentine and the ultrasonically derived modulus of elasticity.