julilili42/papers huggingface dataset:
Integration of Brassinosteroid and Phytosulfokine Signalling Controls Vascular Cell Fate in the Arabidopsis Root
2018-01-08

Abstract Multicellularity arose independently in plants and animals, but invariably requires robust determination and maintenance of cell fate. This is exemplified by the highly specialized water-and nutrient-conducting cells of the plant vasculature, which are specified long before their commitment to terminal differentiation. Here, we show that the hormone receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is required for root vascular cell fate maintenance, as BRI1 mutants show ectopic xylem in procambial position. However, this phenotype is unrelated to classical brassinosteroid signalling outputs. Instead, BRI1 is required for the expression and function of its interaction partner RECEPTOR-LIKE PROTEIN 44 (RLP44), which, in turn, associates with the receptor for the peptide hormone phytosulfokine (PSK). We show that PSK signalling is required for the maintenance of procambial cell identity and is quantitatively controlled by RLP44, which promotes complex formation between the receptor for PSK and its co-receptor. Mimicking the loss of RLP44, PSK-related mutants show ectopic xylem in the position of procambium, whereas rlp44 can be rescued by exogenous PSK. Based on these findings, we propose that RLP44 controls cell fate by connecting BRI1 and PSK signalling, providing a mechanistic framework for the integration of signalling mediated by the plethora of plant receptor-like kinases at the plasma membrane.
Distinct Beta-band Oscillatory Circuits Underlie Corticospinal Gain Modulation
2018-01-09

Rhythmic synchronization of neurons is known to affect neuronal interactions. In the motor system, oscillatory power fluctuations modulate corticospinal excitability. However, previous research addressing phase-specific gain modulation in the motor system has resulted in contradictory findings. It remains unclear how many time windows of increased responsiveness each oscillatory cycle provides. Moreover, we still lack conclusive evidence as to whether the motor cortex entails an intrinsic response modulation along the rhythm cycle, as shown for spinal neurons. We investigated this question with single-pulse transcranial magnetic stimulation over the primary motor cortex at rest. Application of near-motor threshold stimuli revealed a frequency- and phase-specific gain modulation at both cortical and spinal level, independent of the spontaneous oscillatory power fluctuations at each level. We detected bilateral sensorimotor circuits in the lower beta-band (14-17 Hz) and unilateral corticospinal circuits in the upper beta-band (20-24 Hz). These findings provide novel evidence that intrinsic activity in the human motor cortex modulates input gain along the beta oscillatory cycle within distinct circuits. In accordance with periodic alternations of synchronous hyper- and depolarization, increased neuronal responsiveness occurred once per oscillatory beta cycle. This information may lead to new brain state-dependent and circuit-specific interventions for targeted neuromodulation.
Divalproex sodium modulates nuclear localization of ataxin‐3 and prevents cellular toxicity caused by expanded ataxin‐3
2018-01-09

Summary Background &amp; Aims Spinocerebellar ataxia type 3 ( SCA 3), also known as Machado‐Joseph disease ( MJD ), is an autosomal dominantly inherited neurodegenerative disorder and the most common form of SCA worldwide. It is caused by the expansion of a polyglutamine (polyQ) tract in the ataxin‐3 protein. Nuclear localization of the affected protein is a key event in the pathology of SCA 3 via affecting nuclear organization, transcriptional dysfunction, and seeding aggregations, finally causing neurodegeneration and cell death. So far, there is no effective therapy to prevent or slow the progression of SCA 3. Methods In this study, we explored the effect of divalproex sodium as an HDAC i in SCA 3 cell models and explored how divalproex sodium interferes with pathogenetic processes causing SCA 3. Results We found that divalproex sodium rescues the hypoacetylation levels of histone H3 and attenuates cellular cytotoxicity induced by expanded ataxin‐3 partly via preventing nuclear transport of ataxin‐3 (particularly heat shock‐dependent). Conclusion Our study provides novel insights into the mechanisms of action of divalproex sodium as a possible treatment for SCA 3, beyond the known regulation of transcription.
Dynamic and Quantitative Assessment of Blood Coagulation Status with an Oscillatory Rheometer
2018-01-09

During open heart surgery, the haemostasis status of a patient has to be monitored permanently in order to quickly and reliably detect bleeding or coagulation-based disorders. Currently, no single medical device is available to provide a comprehensive solution for monitoring the coagulation status (coagulation, platelets and fibrinolysis). We intend to approach this problem with a rheological method. Here, we compared the performance of an oscillatory rheometer with a medical reference device, a ball coagulometer. Measuring the extrinsic coagulation (prothrombin time; PT), various heparin concentrations (0.5–2.0 IU/mL) could be differentiated and also discriminated from the intrinsic coagulation (activated partial thromboplastin time; aPTT) providing comparable clotting times between rheometer and ball coagulometer. In addition, the oscillatory rheometer was capable to detect the antagonising of heparin with the equimolar concentration of protamine and also the titration of various protamine concentrations (0.5–3.0 IU/mL) to a fixed heparin concentration (2 IU/mL). The addition of increasing concentrations of heparin to citrated blood prolonged the clotting time (CT), changed the slope calculated by linear regression of the elastic and viscous shear moduli (i.e., information of the coagulation process) and changed the value of the shear moduli at the end of the measurement (300 s). These results indicate that the oscillatory rheometer is capable to dynamically measure the haemostasis status with different activators and various inhibitor concentrations.
Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia
2018-01-10

Among surviving extremely preterm infants, the rate of neurodevelopmental disability at 2 years did not differ significantly between infants who received early inhaled budesonide for the prevention of bronchopulmonary dysplasia and those who received placebo, but the mortality rate was higher among those who received budesonide. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190 .).
Genome Sequence of Galleria mellonella (Greater Wax Moth)
2018-01-10

ABSTRACT The larvae of the greater wax moth, Galleria mellonella , are pests of active beehives. In infection biology, these larvae are playing a more and more attractive role as an invertebrate host model. Here, we report on the first genome sequence of Galleria mellonella .
Effects of sleep on the realization of complex plans
2018-01-10

Summary Sleep consolidates newly encoded memories, particularly those memories that are relevant for future behaviour. This study explored whether sleep facilitates the successful execution of relatively complex plans in the future. We applied the Dresden Breakfast Task, in which subjects are instructed to prepare a virtual breakfast comprising several tasks (e.g. table‐setting, preparing eggs). After forming a detailed plan how to realize these tasks, the sleep group ( n = 17) spent a night of sleep at home, monitored by polysomnography, and the wake group ( n = 19) spent a normal day awake, monitored by actigraphy. After a 12‐h interval, all participants were asked to prepare the virtual breakfast. Contrary to our hypothesis, overall performance in breakfast preparation did not differ significantly between the sleep and wake groups. However, sleep participants performed better in one of six tasks, specifically the ‘table‐setting’ task ( P &lt; 0.01), which was driven by higher scores in a subtask measuring the correct position of the tableware ( P &lt; 0.01). Additional exploratory analyses revealed that a significant number of wake participants performed below the minimal score of the sleep group ( P &lt; 0.01) and sleep participants achieved the maximal score in significantly more subtasks than wake participants (57% versus 27%; P = 0.018). Plan adherence, assessing how well participants adhered to their own previously developed plan, did not differ between the sleep and wake groups. These findings provide the first evidence that sleep may support some aspects of the realization of complex, somewhat naturalistic plans .
High prevalence of dihydrofolate reductase gene mutations inPlasmodium falciparumparasites among pregnant women in Nigeria after reported use of sulfadoxine-pyrimethamine
2018-01-10

This study assesses the prevalence of asymptomatic Plasmodium falciparum parasitemia positivity and P. falciparum dihydrofolate reductase (pfdhfr) mutations in parasite isolates among pregnant women in Southwest Nigeria. Plasmodium falciparum parasitemia was confirmed by microscopy and nested PCR in 200 pregnant women attending antenatal care. The prevalence of pfdhfr polymorphisms was determined by direct sequencing of the gene fragments containing the C50R, N51I, C59R, S108N, and I164L mutations. Information on the use of antimalarial drugs and methods applied to prevent malaria were obtained by a questionnaire. The prevalence of asymptomatic P. falciparum infection was 30% (60/200). The frequency of the pfdhfr triple-mutant alleles (N51I, C59R, and S108N) was 63% (38/60); none of the isolates carried the I164L mutation. Among the investigated pregnant women, 40% used un-prescribed antimalarials such as dihydroartemisinin (18%), chloroquine (14%) or pyrimethamine (9%), while only 20.5% used sulfadoxine-pyrimethamine for prevention and 39.5% did not use any drug. The prevalence of P. falciparum parasitemia (37%) was higher among pregnant women who had not taken any antimalarial drugs. A significant difference in the prevalence of the pfdhfr triple-mutant alleles was observed among women who took SP (90%) compared to those who did not take any drug (82%) and women who took dihydroartemisinin (67%) p = 0.007). Poor adherence to the World Health Organisation (WHO) strategies for malaria prevention among pregnant women was observed in addition to high prevalence of pfdhfr mutations. These findings underline the need to improve control of malaria among pregnant women in the study area.
The effects of taxanes, vorinostat and doxorubicin on growth and proliferation of Echinococcus multilocularis metacestodes assessed with magnetic resonance imaging and simultaneous positron emission tomography
2018-01-10

Cytostatic drugs used in cancer therapy were evaluated for their capacity to inhibit <i>Echinococcus multilocularis</i> metacestode growth and proliferation. Metacestode tissues were exposed <i>in vitro</i> to docetaxel, doxorubicin, navelbine, paclitaxel, and vorinostat for 1 week, then incubated in drug-free culture, and thereafter metacestodes were injected into the peritoneum of <i>Meriones unguiculatus</i>. Magnetic resonance imaging (MRI) and simultaneous positron emission tomography (PET) were applied to monitor <i>in vivo</i> growth of drug-exposed <i>E. multilocularis</i> in <i>Meriones</i>. At 3 month p.i., docetaxel (at 10 μM, 5 μM and 2 μM) inhibited <i>in vivo</i> growth and proliferation of <i>E. multilocularis</i>, and at 5 months p.i., only in the 2 μM docetaxel exposure group 0.3 cm <b><sup>3</sup></b> of parasite tissue was found. With paclitaxel and navelbine the <i>in vivo</i> growth of metacestodes was suppressed until 3 months p.i., thereafter, parasite tissues enlarged up to 3 cm <b><sup>3</sup></b> in both groups. <i>E. multilocularis</i> tissues of more than 10 g developed in <i>Meriones</i> injected with metacestodes which were previously exposed <i>in vitro</i> to doxorubicin, navelbine, paclitaxel or vorinostat. In <i>Meriones</i> infected with metacestodes previously exposed to docetaxel, the <i>in vivo</i> grown parasite tissues weighted 0.2 g. <i>In vitro</i> cultured <i>E. multilocularis</i> metacestodes exposed to docetaxel did not produce vesicles until 7 weeks post drug exposure, while metacestodes exposed to doxorubicin, navelbine and vorinostat proliferated continuously. In summary, docetaxel, and less efficaciously paclitaxel, inhibited <i>in vivo</i> and <i>in vitro</i> parasite growth and proliferation, and these observations suggest further experimental studies with selected drug combinations which may translate into new treatment options against alveolar echinococcosis.
Analysis of Operative Techniques of Fractures of the First Metacarpal Base
2018-01-10

Over time, the operative treatment of extra-articular and intra-articular fractures of the first metacarpal base has gained significant importance, and at present, there are many operative strategies available because of the different osteosynthesis procedures in practice today.In this retrospective cohort study, we analyze the possible differences between 2 distinguished operative osteosynthesis techniques, in terms of patient outcome, operation time, duration of radiation exposure, and postoperative radiographic results.Fifty-two patients operated on for first metacarpal extra-articular or intra-articular base fracture were investigated retrospectively by means of records. After reduction, osteosynthesis was performed on 34 patients with K-wires (group I), and on 18 patients with plates and/or screws (group II). Of the 52 patients, 19 were available for a prospective follow-up examination.After analyzing the operation time, a significant difference between the 2 operative techniques for epibasal and Bennett fractures (P = 0.0089 and P = 0.02) was recorded. Furthermore, for the time of radiation exposure, no significant difference could be detected. Also, no statistical difference was found between the 2 analyzed groups in terms of patient outcomes and postoperative radiographic results.The determined data of the operated extra-articular and intra-articular first metacarpal base fractures revealed approximately equal results for patient outcome, postoperative x-ray results, and time of radiation exposure during the operation. After analyzing the operation time of epibasal and Bennett fractures, we can recommend that the K-wire fixation is superior to the plate and/or screw osteosynthesis as a treatment, because of the associated benefits of keeping costs low without harming the patient in the long term.
The Immune Checkpoint Modulator OX40 and Its Ligand OX40L in NK-Cell Immunosurveillance and Acute Myeloid Leukemia
2018-01-11

Abstract The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly, these cells are being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer of ex vivo expanded polyclonal NK cells (pNKC). Here, we analyzed whether and how OX40 and its ligand (OX40L) influence NK-cell function and antileukemia reactivity. We report that OX40 is expressed on leukemic blasts in a substantial percentage of patients with acute myeloid leukemia (AML) and that OX40 can, after stimulation with agonistic OX40 antibodies, mediate proliferation and release of cytokines that act as growth and survival factors for the leukemic cells. We also demonstrate that pNKC differentially express OX40L, depending on the protocol used for their generation. OX40L signaling promoted NK-cell activation, cytokine production, and cytotoxicity, and disruption of OX40–OX40L interaction impaired pNKC reactivity against primary AML cells. Together, our data implicate OX40/OX40L in disease pathophysiology of AML and in NK-cell immunosurveillance. Our findings indicate that effects of the OX40–OX40L receptor–ligand system in other immune cell subsets and also malignant cells should be taken into account when developing OX40-targeted approaches for cancer immunotherapy. Cancer Immunol Res; 6(2); 209–21. ©2018 AACR.
Insect hibernation on urban green land: a winter-adapted mowing regime as a management tool for insect conservation
2018-01-11

Insect conservation is challenging on various ecological scales. One largely neglected aspect is the quality of undisturbed hibernation sites. This study aims to fill a lack of knowledge concerning insect hibernation on uncut meadows persisting in urban green spaces during the winter season in a middle-sized town in south Germany. During two years of sampling, 13,511 insect specimens of the orders Heteroptera, Hymenoptera, Coleoptera and Diptera were caught from their winter stands. The specimens were assigned to 120 families and 140 taxonomic species were determined from the orders Heteroptera, Coleoptera and Diptera and 324 morphotypes from the orders Hymenoptera, Coleoptera and Diptera. The data indicate the importance of winter fallows for insect hibernation. Unmown meadows offer additional plant structures in winter (flower heads, stems, tufts and leaves) that are absent from mown ones. This increased structural diversity results in both higher species diversity and numbers of insect individuals during spring emergence. The results of this study thus emphasise the value of unmown structures for insect conservation and suggest a mosaic-like cutting maintenance of meadows, way- and river-sides and other green infrastructure in both the urban area and the open landscape.
Synthesis of Benzofuranones via Palladium‐Catalyzed Intramolecular Alkoxycarbonylation of Alkenylphenols
2018-01-11

Abstract Herein, a new catalytic system to synthesize benzofuranones is reported. A palladium‐catalyzed intramolecular alkoxycarbonylation is employed to generate 3‐substituted‐benzofuran‐2(3 H )‐ones from alkenylphenols under mild reaction conditions, linked to an ex situ formation of CO from N ‐formylsaccharin. The carefully chosen catalytic system enables an efficient reaction with a novel functional group tolerance, despite the high polymerization tendency of the starting material.
Reanalysis of Chinese Treponema pallidum samples: all Chinese samples cluster with SS14-like group of syphilis-causing treponemes
2018-01-11

We reanalyzed the primary sequencing data (Project Number PRJNA305961) from the Sun et al. publication with respect to the molecular basis of Lineage 2. While Sun et al. based the analysis on several selected genomic single nucleotide variants (SNVs) and a subset of highly variable but phylogenetically poorly informative genes, which may confound the phylogenetic analysis, our reanalysis primarily focused on a complete set of whole genomic SNVs. Based on our reanalysis, only two separate TPA clusters were identified: one consisted of Nichols-like TPA strains, the other was formed by the SS14-like TPA strains, including all Chinese strains.
Optimization of the surface modification process of cross‐linked polythiol‐coated chiral stationary phases synthesized by a two‐step thiol‐ene click reaction
2018-01-11

Abstract A new platform technology for the preparation of stable chiral stationary phases was successfully optimized. The chiral selector tert ‐butylcarbamoylquinine was firstly covalently connected to the polymer poly(3‐mercaptopropyl)methylsiloxane by thiol‐ene click reaction. Secondly, the quinine carbamate functionalized polysiloxane conjugate was coated onto the surface of vinyl modified silica particles and cross‐linked via thiol‐ene click reaction. The amount of polysiloxane, chiral selector, radical initiator, reaction solvent (chloroform and methanol), reaction time, and pore size of the supporting silica particles were varied and systematically optimized in terms of achievable plate numbers while maintaining simultaneously enantioselectivity. The optimization was based on elemental analysis data, chromatographic results, and H/u‐curves (Van Deemter) of the resultant chiral stationary phases. The results suggest that better chromatographic efficiency (higher plate numbers) at equal enantioselectivity can be achieved with methanol (a poor solvent for the polysiloxane that is dispersed rather than dissolved) and a lower film thickness of quinine carbamate functionalized polysiloxane. In this study, chiral stationary phases based on 100 Å silica slightly outperformed 200 Å silica particles (each 5 μm). The optimized two step material exhibited significantly reduced mass transfer resistance compared to the one step material and equal performance as a brush‐type chiral stationary phase.
Nuremberg’s Noble Servant: Werner von Parsberg (d. 1455) between Town and Nobility in Late Medieval Germany*
2018-01-11

The nobleman Werner von Parsberg served the imperial town of Nuremberg between 1430 and his death in 1455 as a mounted retainer and (from 1442) as the town’s imperial chief magistrate. In 1450 he carried Nuremberg’s standard in battle during the Second South German Towns’ War. This long record of close engagement with Nuremberg contrasts with the tradition of reading ‘town’ and ‘nobility’ in Germany as mutually exclusive and inherently antagonistic. In Parsberg’s time this was a position advocated by Nuremberg’s opponents amongst the territorial princes and rural nobility, and from the Enlightenment onwards a more rigid version of this dichotomy was projected back onto the late Middle Ages. This perceived opposition between ‘town’ and ‘nobility’ denied the possibility of meaningful cooperation between townspeople and rural nobles: all such relationships have consequently been described as the result of economic and political weakness on the part of the nobles concerned. Recent research, however, suggests that a re-examination of these relationships is necessary, and the case of Werner von Parsberg offers a model for such a reassessment. This article shows that Parsberg’s service for Nuremberg was not a symptom of weakness, but part of an assertive strategy to advance the independence from princely authority of his family’s lordship in the Upper Palatinate. Through this appreciation of the factors supporting town–noble cooperation in the late Middle Ages we are better able to understand the formation and development of the dialectic of town and nobility as a way of understanding German society.