julilili42/papers huggingface dataset:
Direct Microscopic Proof of the Fermi Level Pinning Gas-Sensing Mechanism: The Case of Platinum-Loaded WO3
2019-12-13

It is widely known that the sensing characteristics of metal oxides are drastically changed through noble metal oxide surface additives. Using operando infrared spectroscopy it was identified that the Fermi level pinning mechanism dominates the sensor response of platinum-loaded WO<sub>3</sub>. Spectroscopy, however, provides information about the sample only on average. Traditional microscopy offers structural information but is typically done in vacuum and on unheated sensors, very different than the operation conditions of metal oxide gas sensors. Here, state-of-the-art in situ scanning transmission electron microscopy offers spatially resolved information on heated samples at atmospheric pressure in varying gas atmospheres. As a result it was possible to directly couple microscopically observed structural changes in the surface noble metal nanoclusters with IR spectra and sensor responses. On the basis of the findings, the dominant Fermi level pinning mechanism could be validated. The presented work demonstrates the benefits of coupling in situ microscopy with operando spectroscopy in order to elucidate the sensing mechanism of metal oxides.
The Striking Flower-in-Flower Phenotype of Arabidopsis thaliana Nossen (No-0) is Caused by a Novel LEAFY Allele
2019-12-13

The transition to reproduction is a crucial step in the life cycle of any organism. In Arabidopsis thaliana the establishment of reproductive growth can be divided into two phases: Firstly, cauline leaves with axillary meristems are formed and internode elongation begins. Secondly, lateral meristems develop into flowers with defined organs. Floral shoots are usually determinate and suppress the development of lateral shoots. Here, we describe a transposon insertion mutant in the Nossen accession with defects in floral development and growth. Most strikingly is the outgrowth of stems from the axillary bracts of the primary flower carrying secondary flowers. Therefore, we named this mutant flower-in-flower (fif). However, the transposon insertion in the annotated gene is not the cause for the fif phenotype. By means of classical and genome sequencing-based mapping, the mutation responsible for the fif phenotype was found to be in the LEAFY gene. The mutation, a G-to-A exchange in the second exon of LEAFY, creates a novel lfy allele and results in a cysteine-to-tyrosine exchange in the α1-helix of LEAFY’s DNA-binding domain. This exchange abolishes target DNA-binding, whereas subcellular localization and homomerization are not affected. To explain the strong fif phenotype against these molecular findings, several hypotheses are discussed.
HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice
2019-12-13

Abstract Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors while cones remain initially unaffected. Cone death follows rod death secondarily due to increased oxidative stress, inflammation, and loss of structural and nutritional support provided by rods. Here, we show that secondary cone cell death in animal models for RP was associated with an increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at a late stage of the disease, when majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival. Moreover, the surviving cones remained light sensitive and initiated light-driven ganglion cell responses. RNA-seq analysis of protected cones demonstrated that HDAC inhibition led to multi-level protection via regulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique possibility for a targeted pharmacological protection of both primary degenerating rods and secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients independent of the disease stage.
Amplification of 7p12 Is Associated with Pathologic Nonresponse to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer
2019-12-13

Pathologic downstaging (pDS) to neoadjuvant chemotherapy (NAC) is one of the most important predictors of survival in muscle-invasive bladder cancer (MIBC). The use of NAC is limited as pDS is only achieved in 30% to 40% of cases and predictive biomarkers are still lacking. We performed a comprehensive immunomolecular biomarker analysis to characterize the role of immune cells and inhibitory checkpoints, genome-wide frequencies of copy number alterations, mutational signatures in whole exome, and tumor mutational burden in predicting NAC response. Our retrospective study included 23 primary MIBC patients who underwent NAC, followed by radical cystectomy. pDS to NAC was a significant prognostic factor for better recurrence-free survival (P < 0.001), with a median time to recurrence of 41.2 versus 5.5 months in nonresponders. DNA damage repair alterations were noticed in 38.1% (n = 8), confirming a positive correlation with high tumor mutational burden (P = 0.007). Chromosomal 7p12 amplification, including the genes HUS1, EGFR, ABCA13, and IKZF1, predicted nonresponse in patients with a sensitivity, a negative predictive value, and a specificity of 71.4%, 87.5%, and 100%, respectively. Total count of CD3<sup>+</sup> T cells/mm<sup>2</sup> tumor was a significant predictor of NAC response. In conclusion, 7p12 amplification may predict nonresponse to NAC and worse survival in MIBC. Multicenter, prospective trials with sufficient statistical power may further fortify these findings.
Optimisation of the drill-in behaviour of the EcoFit® SC threaded cup
2019-12-13

Abstract Threaded cups show good clinical results when implanted correctly. In clinical use, multiple cases with an incomplete placement of the EcoFit threaded cup (implantcast) were observed. This behaviour could not be explained intra- and postoperatively. The aim of this study was to compare and optimise the drill-in-behaviour of the EcoFit cup in a biomechanical investigation. EcoFit cup sizes 46, 50 and 54 mm were compared with the SC cup (Aesculap) size 50 mm. Foam blocks (Sawbones) of density 0.16 g/ml (pcf 10), 0.32 g/ml (pcf 20) and 0.48 g/ml (pcf 30) were used. After standardised placement using a universal testing system (n = 8 per group), the primary stability, the overhang of the cups and the drill-in behaviour were measured. Overreamings of 1 and 2 mm were performed (pcf 20, n = 8) for the EcoFit cup size 50 and the primary stability as well as the overhang measurements were examined. Measurements of the cup diameter, thread depth and thread pitch were performed on three-dimensional (3D) images of the cup size 50 mm. The drill-in behaviour was different between the EcoFit and the SC cups. Even with maximum torque, the EcoFit cup could not be positioned as deep as the SC cup in standard reaming conditions (overhang of 1.1 ± 0.4 mm for the EcoFit size 50 in pcf 20 and of −0.01 ± 0.2 mm for the SC cup). The primary stability was lower for the EcoFit cup in comparison to the SC cup (128.8 ± 3.2 Nm vs. 138.6 ± 9.1 Nm, p = 0.0291). With overreaming to 51 mm, a deeper positioning of the EcoFit was possible (overlap of −0.3 ± 0.1, comparable to the SC cup). The overreaming of the cavity also led to a significantly higher primary stability of 143.4 ± 3.7 Nm (p &lt; 0.001) comparable to the unaltered condition (128.8 ± 3.2 Nm). Overreaming to 52 mm had no further advantage in terms of primary stability or overhang. The geometric measurements showed significant differences as well. The previously clinically observed difficulties in inserting the cup were confirmed by this study. By overreaming to 51 mm, the drill-in behaviour, the primary stability and the measured overhang were comparable to the reference cup. The obtained results suggest that the extension of the acetabulum cavity to 51 mm while using the implantcast EcoFit size 50 should be implemented in clinical applications.
Long-range quantum coherence of the photosystem 2 complexes in living cyanobacteria
2019-12-13

Abstract The first step in photosynthesis is an extremely efficient energy transfer mechanism, which is difficult to be explained by classical short-range energy migration (“hopping”) and led to the debate to which extent quantum coherence is involved in the energy transfer between the photosynthetic pigments. Embedding living cyanobacteria between the mirrors of an optical microresonator and using low intensity white light irradiation we observe vacuum Rabi splitting in the transmission and fluorescence spectra as a result of strong light matter coupling of the chlorophyll and the resonator modes. The Rabi-splitting scales with the number of chlorophyll a pigments involved in coherent coupling indicating forming a polaritonic state which is delocalized over the entire cyanobacterial thylakoid system, down to the single photon level. Our data provide evidence that a delocalized polaritonic state is the basis of the extremely high energy transfer efficiency under natural conditions.
Humans use a local code for tactile perception
2019-12-13

Abstract Humans are classically thought to use either spectral decomposition or averaging to identify vibrotactile signals. These are general purpose ‘global’ codes that require integration of the signal over long stretches of time. Natural vibrotactile signals, however, likely contain short signature events that can be detected and used for inference of textures, instantaneously, with minimal integration, suggesting a hitherto ignored ‘local code’. Here, by employing pulsatile stimuli and a change detection psychophysical task, we studied whether humans make use of local cues. We compared three local cues based on instantaneous skin position and its derivatives, as well as six global cues, calculated as summed powers (with exponents 1,2, and 3) of velocity and acceleration. Deliberate manipulation of pulse width and amplitude (local+global) as well as pulse frequency (global) allowed us to disentangle local from global codes. The results singled out maximum velocity, an instantaneous code, as a likely and dominant coding variable that humans rely on to perform the task. Comparing stimuli containing versus lacking local cues, demonstrated that performances exclusively using global cues are rather poor compared to situations where local ones are available as well. Our results are in line with the notion that humans not only do use local cues but that local cues may even play a dominant role in perception. Our results parallel previous results in rodents, pointing to the possibility that quite similar coding strategies evolved in whisker and finger tactile systems. Significance statement The brain is believed to select coding symbols in sensory signals that would most efficiently convey functionally relevant information about the world. For instance, the visual system is widely believed to use spatially local features, like edge orientation, to delineate a visual scene. For the tactile system only global, general purpose coding schemes have been discussed so far. Based on the insight that moving contacts, characteristic for active touch, feature short-lived stick-slip events, frictional movements that transfer fair amounts of texture information, one should expect the brain to use a temporally local code, extracting and instantaneously analyzing short snippets of skin movement. Here, we provide the first analytical psychophysical evidence in humans that this indeed is the case.
Expression and function of theMedicago truncatulalysin motif receptor‐like kinase (LysM‐RLK) gene family in the legume–rhizobia symbiosis
2019-12-13

The Medicago truncatula genome, version 4.0, is predicted to contain 22 lysin motif receptor-like kinase (LysM-RLK) genes, which can be divided into two sub-families. The 11 predicted LYK genes have many introns and are predicted to encode receptor proteins with active kinase domains. The 11 LYR genes have no or few introns and for most of them the kinase domain is predicted to lack key residues normally required for catalytic activity. A gene from each of the LYR and LYK sub-families, NFP and LYK3 respectively, play essential roles in establishment of the legume–Rhizobium symbiosis. NFP and LYK3 are both required for Rhizobium induced root hair curling, infection, and nodule organogenesis, and, in addition, NFP is required for all Nod factor responses. All other members of the family are expressed in either roots or nodules and some of them are regulated either by treatment of roots with lipochitooligosaccharidic Nod factor signals or by Rhizobium, suggesting that these genes could also play roles in the symbiosis. This article describes the current state of our knowledge of the regulation and roles of this important receptor-like kinase family in establishment of the symbiosis between M. truncatula and its Rhizobial symbiont.
Depletion of Akt1 and Akt2 Impairs the Repair of Radiation-Induced DNA Double Strand Breaks via Homologous Recombination
2019-12-14

Homologous recombination repair (HRR), non-homologous end-joining (NHEJ) and alternative NHEJ are major pathways that are utilized by cells for processing DNA double strand breaks (DNA-DSBs); their function plays an important role in the radiation resistance of tumor cells. Conflicting data exist regarding the role of Akt in homologous recombination (HR), i.e., the regulation of Rad51 as a major protein of this pathway. This study was designed to investigate the specific involvement of Akt isoforms in HRR. HCT116 colon cancer cells with stable AKT-knock-out and siRNA-mediated AKT-knockdown phenotypes were used to investigate the role of Akt1 and Akt2 isoforms in HR. The results clearly demonstrated that HCT116 AKT1-KO and AKT2-KO cells have a significantly reduced Rad51 foci formation 6 h post irradiation versus parental cells. Depletion of Akt1 and Akt2 protein levels as well as inhibition of Akt kinase activity resulted in an increased number of residual-γH2AX in CENP-F positive cells mainly representing the S and G2 phase cells. Furthermore, inhibition of NHEJ and HR using DNA-PK and Rad51 antagonists resulted in stronger radiosensitivity of AKT1 and AKT2 knockout cells versus wild type cells. These data collectively show that both Akt1 and Akt2 are involved in DSBs repair through HRR.
Ongoing tissue changes in an experimentally mummified human leg
2019-12-14

Abstract Artificial mummification has been used since antiquity and is best known from ancient Egypt. Despite ancient Egyptian mummies being studied for several decades, the mummification techniques of that time are not well understood. Modern mummification experiments involving animal and human tissues have contributed additional insights relevant to a broad field of research. In the current study, we present follow‐up results of an experiment on artificial mummification, which began in 2009. A human leg was artificially mummified and monitored for almost a year with histological, molecular, and radiological techniques. Since then, it has remained in a dry, natron salt blend for 9 years. The current analyses show further progression of dehydration and tissue alterations, as well as DNA degradation, suggesting an ongoing process. Our results add new insights into the mechanisms of tissue mummification. Taking into account that the process is still ongoing, further research is required, including a re‐evaluation of the human leg in the future.
Positional information and tissue scaling during development and regeneration
2019-12-15

ABSTRACT In order to contribute to the appropriate tissues during development, cells need to know their position within the embryo. This positional information is conveyed by gradients of signaling molecules, termed morphogens, that are produced in specific regions of the embryo and induce concentration-dependent responses in target tissues. Positional information is remarkably robust, and embryos often develop with the correct proportions even if large parts of the embryo are removed. In this Review, we discuss classical embryological experiments and modern quantitative analyses that have led to mechanistic insights into how morphogen gradients adapt, scale and properly pattern differently sized domains. We analyze these experimental findings in the context of mathematical models and synthesize general principles that apply to multiple systems across species and developmental stages.
A Praziquantel Treatment Study of Immune and Transcriptome Profiles inSchistosoma haematobium-Infected Gabonese Schoolchildren
2019-12-15

Abstract Background Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms. Methods Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed. Results Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4+CD25+FOXP3+ T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness. Conclusions Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4+CD25+FOXP3+ T-cells, cellular metabolism, and transcription factors involved in anergy.
Susceptibility to auditory closed-loop stimulation of sleep slow oscillations changes with age
2019-12-15

Abstract Background Cortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate sleep-dependent memory consolidation. Experiments utilising auditory closed-loop stimulation to enhance these oscillations have shown great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups. Objective We examined the possibility of enhancing SOs and performance on different memory tasks in a healthy older population using auditory closed-loop stimulation and contrast effects to a young adult cohort. Methods In a within-subject design, subjects (n = 17, 55.7 ± 1.0 years, 9 female) received auditory click stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to those reported previously in a younger cohort (n = 11, 24.2 ± 0.9 years, 8 female). Results Overnight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups. Conclusions Our findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations. Highlights Auditory closed-loop stimulation induced SOs and sleep spindles in older subjects Stimulation effects were reduced and overall susceptibility diminished with age Slow oscillation and sleep spindle dynamics deviated from those in younger subjects Stimulation shows no evidence for memory effect in older subjects
Ancient DNA suggests modern wolves trace their origin to a Late Pleistocene expansion from Beringia
2019-12-16

Abstract Grey wolves ( Canis lupus ) are one of the few large terrestrial carnivores that have maintained a wide geographical distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the Late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single Late Pleistocene population. Both the geographical origin of this ancestral population and how it became widespread remain unknown. Here, we used a spatially and temporally explicit modelling framework to analyse a data set of 90 modern and 45 ancient mitochondrial wolf genomes from across the Northern Hemisphere, spanning the last 50,000 years. Our results suggest that contemporary wolf populations trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum, and that this process was most likely driven by Late Pleistocene ecological fluctuations that occurred across the Northern Hemisphere. This study provides direct ancient genetic evidence that long‐range migration has played an important role in the population history of a large carnivore, and provides insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because Late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog.