bluuebunny/crossref_metadata_2025_split huggingface dataset:
A healthy individual with a homozygous PTCH2 frameshift variant: Are variants of PTCH2 associated with nevoid basal cell carcinoma syndrome?
Authors: Altaraihi M. , Wadt K. , Ek J. , Gerdes A. M. , Ostergaard E. 
Published: February 2019

AbstractVariants in PTCH2 have been described to be associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS). We report a family with a healthy female who is homozygous for a frameshift variant, c.269delG, p.(Gly90Alafs*4), in PTCH2 and her heterozygous daughter. The variant predicts a frameshift and a premature stop codon. A summary of reported heterozygous individuals with germline PTCH2 variants along with the existence of a healthy homozygous individual question whether variants in PTCH2 are associated with NBCCS.
Sensing intracellular calcium ions using a manganese-based MRI contrast agent
Authors: Barandov Ali , Bartelle Benjamin B. , Williamson Catherine G. , Loucks Emily S. , Lippard Stephen J. , Jasanoff Alan 
Published: February 2019

AbstractCalcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic contrast agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI contrast when stimulated with pharmacological agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI.
STAT1 signaling shields T cells from NK cell-mediated cytotoxicity
Authors: Kang Yu Hui , Biswas Amlan , Field Michael , Snapper Scott B. 
Published: February 2019

AbstractThe JAK-STAT pathway critically regulates T-cell differentiation, and STAT1 is postulated to regulate several immune-mediated diseases by inducing proinflammatory subsets. Here we show that STAT1 enables CD4+T-cell-mediated intestinal inflammation by protecting them from natural killer (NK) cell-mediated elimination.Stat1−/−T cells fail to expand and establish colitis in lymphopenic mice. This defect is not fully recapitulated by the combinatorial loss of type I and II IFN signaling. Mechanistically,Stat1−/−T cells have reduced expression ofNlrc5and multiple MHC class I molecules that serve to protect cells from NK cell-mediated killing. Consequently, the depletion of NK cells significantly rescues the survival and spontaneous proliferation ofStat1−/−T cells, and restores their ability to induce colitis in adoptive transfer mouse models.Stat1−/−mice however have normal CD4+T cell numbers as innate STAT1 signaling is required for their elimination. Overall, our findings reveal a critical perspective on JAK-STAT1 signaling that might apply to multiple inflammatory diseases.
A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells
Authors: Ysrayl Binah baht , Balasubramaniam Muthukumar , Albert Ife , Villalta Fernando , Pandhare Jui , Dash Chandravanu 
Published: February 2019

AbstractCocaine use is associated with breach in the blood brain barrier (BBB) and increased HIV-1 neuro-invasion. We show that the cellular enzyme “Prolidase” plays a key role in cocaine-induced disruption of the BBB. We established a barrier model to mimic the BBB by culturing human brain microvascular endothelial cells (HBMECs) in transwell inserts. In this model, cocaine treatment enhanced permeability of FITC-dextran suggesting a breach in the barrier. Interestingly, cocaine treatment increased the activity of matrix metallo-proteinases that initiate degradation of the BBB-associated collagen. Cocaine exposure also induced prolidase expression and activity in HBMECs. Prolidase catalyzes the final and rate-limiting step of collagen degradation during BBB remodeling. Knock-down of prolidase abrogated cocaine-mediated increased permeability suggesting a direct role of prolidase in BBB breach. To decipher the mechanism by which cocaine regulates prolidase, we probed the inducible nitric oxide synthase (iNOS) mediated phosphorylation of prolidase since mRNA levels of the protein were not altered upon cocaine treatment. We observed increased iNOS expression concurrent with increased prolidase phosphorylation in cocaine treated cells. Subsequently, inhibition of iNOS decreased prolidase phosphorylation and reduced cocaine-mediated permeability. Finally, cocaine treatment increased transmigration of monocytic cells through the HBMEC barrier. Knock-down of prolidase reduced cocaine-mediated monocyte transmigration, establishing a key role of prolidase in cocaine-induced breach in endothelial cell barrier.
Evolutionary dynamics of the chromatophore genome in three photosynthetic Paulinella species
Authors: Lhee Duckhyun , Ha Ji-San , Kim Sunju , Park Myung Gil , Bhattacharya Debashish , Yoon Hwan Su 
Published: February 2019

AbstractThe thecate amoeba Paulinella is a valuable model for understanding plastid organellogenesis because this lineage has independently gained plastids (termed chromatophores) of alpha-cyanobacterial provenance. Plastid primary endosymbiosis in Paulinella occurred relatively recently (90–140 million years ago, Mya), whereas the origin of the canonical Archaeplastida plastid occurred >1,500 Mya. Therefore, these two events provide independent perspectives on plastid formation on vastly different timescales. Here we generated the complete chromatophore genome sequence from P. longichromatophora (979,356 bp, GC-content = 38.8%, 915 predicted genes) and P. micropora NZ27 (977,190 bp, GC-content = 39.9%, 911 predicted genes) and compared these data to that from existing chromatophore genomes. Our analysis suggests that when a basal split occurred among photosynthetic Paulinella species ca. 60 Mya, only 35% of the ancestral orthologous gene families from the cyanobacterial endosymbiont remained in chromatophore DNA. Following major gene losses during the early stages of endosymbiosis, this process slowed down significantly, resulting in a conserved gene content across extant taxa. Chromatophore genes faced relaxed selection when compared to homologs in free-living alpha-cyanobacteria, likely reflecting the homogeneous intracellular environment of the Paulinella host. Comparison of nucleotide substitution and insertion/deletion events among different P. micropora strains demonstrates that increases in AT-content and genome reduction are ongoing and dynamic processes in chromatophore evolution.
Novel RU486 (mifepristone) analogues with increased activity against Venezuelan Equine Encephalitis Virus but reduced progesterone receptor antagonistic activity
Authors: DeBono Aaron , Thomas David R. , Lundberg Lindsay , Pinkham Chelsea , Cao Ying , Graham J. Dinny , Clarke Christine L. , Wagstaff Kylie M. , Shechter Sharon , Kehn-Hall Kylene , Jans David A. 
Published: February 2019

AbstractThere are currently no therapeutics to treat infection with the alphavirus Venezuelan equine encephalitis virus (VEEV), which causes flu-like symptoms leading to neurological symptoms in up to 14% of cases. Large outbreaks of VEEV can result in 10,000 s of human cases and mass equine death. We previously showed that mifepristone (RU486) has anti-VEEV activity (EC50 = 20 μM) and only limited cytotoxicity (CC50 > 100 μM), but a limitation in its use is its abortifacient activity resulting from its ability to antagonize the progesterone receptor (PR). Here we generate a suite of new mifepristone analogues with enhanced antiviral properties, succeeding in achieving >11-fold improvement in anti-VEEV activity with no detectable increase in toxicity. Importantly, we were able to derive a lead compound with an EC50 of 7.2 µM and no detectable PR antagonism activity. Finally, based on our SAR analysis we propose avenues for the further development of these analogues as safe and effective anti-VEEV agents.
Enhancing the sensitivity of micro magnetic resonance relaxometry detection of low parasitemia Plasmodium falciparum in human blood
Authors: Thamarath Smitha Surendran , Xiong Aoli , Lin Po-Han , Preiser Peter Rainer , Han Jongyoon 
Published: February 2019

AbstractUpon Plasmodium falciparum infection of the red blood cells (RBCs), the parasite replicates and consumes haemoglobin resulting in the release of free heme which is rapidly converted to hemozoin crystallites. The bulk magnetic susceptibility of infected RBCs (iRBCs) is changed due to ferric (Fe3+) paramagnetic state in hemozoin crystallites which induce a measurable change in spin-spin relaxation (transverse relaxation) rate in proton nuclear magnetic resonance (NMR) of iRBCs. Earlier, our group reported that this transverse relaxation rate (R2) can be measured by an inexpensive, portable 0.5 Tesla bench top magnetic resonance relaxometry (MRR) system with minimum sample preparation and is able to detect very low levels of parasitemia in both blood cultures as well as animal models. However, it was challenging to diagnose malaria in human blood using MRR, mainly due to the inherent variation of R2 values of clinical blood samples, caused by many physiological and genotypic differences not related to the parasite infection. To resolve the problem of baseline R2 rates, we have developed an improved lysis protocol for removing confounding molecular and cellular background for MRR detection. With this new protocol and by processing larger volume of blood (>1 ml), we are able to reliably detect very low level of parasitemia (representing early stage of infection, ~0.0001%) with a stable baseline and improved sensitivity using the current MRR system.
Eigenvalues of the covariance matrix as early warning signals for critical transitions in ecological systems
Authors: Chen Shiyang , O’Dea Eamon B. , Drake John M. , Epureanu Bogdan I. 
Published: February 2019

AbstractMany ecological systems are subject critical transitions, which are abrupt changes to contrasting states triggered by small changes in some key component of the system. Temporal early warning signals such as the variance of a time series, and spatial early warning signals such as the spatial correlation in a snapshot of the system’s state, have been proposed to forecast critical transitions. However, temporal early warning signals do not take the spatial pattern into account, and past spatial indicators only examine one snapshot at a time. In this study, we propose the use of eigenvalues of the covariance matrix of multiple time series as early warning signals. We first show theoretically why these indicators may increase as the system moves closer to the critical transition. Then, we apply the method to simulated data from several spatial ecological models to demonstrate the method’s applicability. This method has the advantage that it takes into account only the fluctuations of the system about its equilibrium, thus eliminating the effects of any change in equilibrium values. The eigenvector associated with the largest eigenvalue of the covariance matrix is helpful for identifying the regions that are most vulnerable to the critical transition.
Estimation of the effective reproduction number of influenza based on weekly reports in Miyazaki Prefecture
Authors: Yamauchi Takenori , Takeuchi Shouhei , Yamano Yuko , Kuroda Yoshiki , Nakadate Toshio 
Published: February 2019

AbstractIn Japan, as part of surveillance for seasonal influenza, the number of patients per influenza sentinel site is counted on a weekly basis. Currently, reference values are set for the weekly reported number of influenza cases per sentinel, and pre-epidemic and epidemic warnings are issued based on these values. In this study, we examined the association between these reference values and the effective reproduction number (Rt) using surveillance data for Miyazaki Prefecture collected from 2010 to 2011. There are nine public health centre jurisdictions in this prefecture, and Rt exceeded 1.0 at the time when pre-epidemic warnings were issued in almost all the jurisdictions. Thus, it was indicated that the validity of the reference value was also high for influenza transmission. However, our results indicated the presence of secondary epidemic caused by infections originating both from other jurisdictions and inner jurisdictions, and it is occasionally not possible to evaluate the end of an epidemic in a jurisdiction using only the reference value of termination. It is necessary to establish new methods after considering the situation in the surrounding jurisdictions for more detailed epidemic predictions.
Biphasic changes in spontaneous cardiovagal baroreflex sensitivity during passive hyperthermia
Authors: Turcani Marian , Ghadhanfar Elham 
Published: February 2019

AbstractSuccessful adaptation to passive hyperthermia requires continual adjustment of circulation, which is mediated mainly by the autonomic nervous system. The goal of this study was to explore the alterations in spontaneous cardiovagal baroreflex sensitivity (BRS) during exposure to a hot environment. To continuously follow changes in core body temperature (Tc), haemodynamics, and BRS, male Wistar-Kyoto rats were implanted with telemetric transmitters. BRS at an ambient temperature of 23 °C was not steady but oscillated with a maximum power in the range of 0.02–0.2 Hz. Exposure to hot air immediately shifted the distribution of BRS to higher values, although Tc remained unchanged (37.2 (0.3) °C), and the average BRS changed from 1.3 (0.3) to 3 (1.4) ms.mmHg−1, p < 0.0001. The degree of initial cardiovagal baroreflex sensitization explained 57% of the variability in the time to the onset of arterial pressure decline (p = 0.0114). With an increasing Tc (>38.8 (0.6) °C), BRS non-linearly declined, but haemodynamic parameters remained stable even above a Tc of 42 °C when the cardiovagal baroreflex was virtually non-operative. Abrupt full desensitization of the cardiovagal baroreflex with a muscarinic blocker did not induce arterial pressure decline. Our data indicate that a progressive decrease in BRS during passive hyperthermia does not induce haemodynamic instability. The positive association between initial cardiovagal baroreflex sensitization and the time to the onset of arterial pressure decline may reflect the potential protective role of parasympathetic activation during exposure to a hot environment.
The promiscuous activity of alpha-amylase in biodegradation of low-density polyethylene in a polymer-starch blend
Authors: Karimi M. , Biria D. 
Published: February 2019

AbstractBlending polyolefins with certain types of natural polymers like starch can be beneficial to their biodegradation. The impact of alpha-amylase on the biodegradation of low-density polyethylene (LDPE)-starch blend samples in an aqueous solution was investigated through characterizing their physical, mechanical and chemical properties. Results indicated that the weight and tensile strength of the enzyme treated samples were reduced by 48% and 87% respectively. Moreover, differential scanning calorimetry (DSC) showed an increase in fusion enthalpy of degraded samples which means that the crystallinity has been increased. The biodegradation of LLDPE appeared in Fourier-transform infrared spectroscopy (FT-IR) through the reduction in the intensity of the related peaks. This observation was supported by energy dispersive x-ray spectroscopy (EDXS) analysis where decreasing the percentage of carbon atoms in the treated blend was obtained. Likewise, the gel permeation chromatography (GPC) results pointed to a significant reduction in both the molecular weight and viscosity of LDPE more than 70% and 60% respectively. Furthermore, thermal gravimetric analysis (TGA) affirmed the function of amylase in degradation of the blend. On the basis of the obtained results, it can be claimed that the main backbone of the polymer, as well as the side branches, have been scissored by the enzyme activity. In other words, alpha-amylase has a promiscuous cometabolic effect on biodegradation of LDPE in polymer-starch blends.
Climate and symbioses with ants modulate leaf/stem scaling in epiphytes
Authors: Chomicki Guillaume , Renner Susanne S. 
Published: February 2019

AbstractIn most seed plants, leaf size is isometrically related to stem cross-sectional area, a relationship referred to as Corner’s rule. When stems or leaves acquire a new function, for instance in ant-plant species with hollow stems occupied by ants, their scaling is expected to change. Here we use a lineage of epiphytic ant-plants to test how the evolution of ant-nesting structures in species with different levels of symbiotic dependence has impacted leaf/stem scaling. We expected that leaf size would correlate mostly with climate, while stem diameter would change with domatium evolution. Using a trait dataset from 286 herbarium specimens, field and greenhouse observations, climatic data, and a range of phylogenetic-comparative analyses, we detected significant shifts in leaf/stem scaling, mirroring the evolution of specialized symbioses. Our analyses support both predictions, namely that stem diameter change is tied to symbiosis evolution (ant-nesting structures), while leaf size is independently correlated with rainfall variables. Our study highlights how independent and divergent selective pressures can alter allometry. Because shifts in scaling relationships can impact the costs and benefits of mutualisms, studying allometry in mutualistic interactions may shed unexpected light on the stability of cooperation among species.
In-depth study of the hypercompact H II region G24.78+0.08 A1
Authors: Cesaroni R. , Beltrán M. T. , Moscadelli L. , Sánchez-Monge Á. , Neri R. 
Published: February 2019

Context. The earliest phases of the evolution of a massive star are closely related to the developement of an H II region. Hypercompact H II regions are the most interesting in this respect because they are very young, and hence best suited to study the beginning of the expansion of the ionised gas inside the parental core.
Aims. We have analysed the geometrical and physical structure of the hypercompact H II region G24.78+0.08 A1, making use of new continuum and hydrogen recombination line data (H41α, H63α, H66α, H68α) and data from the literature (H30α, H35α).
Methods. We fit the continuum spectrum with a homogenous, isothermal shell of ionised gas at 104 K and derive the size of the H II region and the Lyman continuum luminosity of the ionising star. We also fit the recombination line spectra emitted from the same shell with a model taking into account expansion at constant speed.
Results. The best fits to the continuum and line spectra allow the derivation of the Lyman continuum luminosity of the ionising star, H II region size, geometrical thickness of the shell, and expansion velocity. Comparison between the 5 cm and 7 mm brightness temperature distributions demonstrates that a thin layer of ionised gas of a few 1000 K at the surface of the H II region is necessary to reproduce the morphology of the continuum emission at both wavelengths.
Conclusions. We confirm that the G24 A1 hypercompact H II region consists of a thin shell ionised by an O9.5 star. The shell is expanding at a speed comparable to the sound speed in the ionised gas. The radius of the H II region exceeds the critical value needed to trap the ionised gas by the gravitational field of the star, consistent with the observed expansion.
Observing the gas component of circumplanetary disks around wide-orbit planet-mass companions in the (sub)mm regime
Authors: Rab Ch. , Kamp I. , Ginski C. , Oberg N. , Muro-Arena G. A. , Dominik C. , Waters L. B. F. M. , Thi W.-F. , Woitke P. 
Published: February 2019

Context. Several detections of wide-orbit planet-mass/substellar companions around young solar-like stars were reported in the last decade. The origin of those possible planets is still unclear, but accretion tracers and VLT/SPHERE observations indicate that they are surrounded by circumplanetary material or even a circumplanetary disk (CPD).
Aims. We want to investigate if the gas component of disks around wide-orbit companions is detectable with current (ALMA) and future (ngVLA; sub)mm telescopes and what constraints such gas observations can provide on the nature of the circumplanetary material and the mass of the companion.
Methods. We applied the radiation thermochemical disk code PRODIMO to model the dust and gas component of passive CPDs and produced realistic synthetic observables. We considered different companion properties (mass, luminosity), disk parameters (mass, size, and dust properties) and radiative environments (background fields) and compared the resulting synthetic observables to telescope sensitivities and existing dust observations.
Results. The main criterion for a successful detection is the size of the CPD. At a distance of about 150 pc, a CPD with an outer radius of about 10 au is detectable with ALMA in about six hours in optically thick CO lines. Other aspects, such as the luminosity, disk inclination, and background radiation fields of the companion, are also relevant and should be considered to optimize the observing strategy for detection experiments.
Conclusions. For most of the known wide-orbit planet-mass companions, their maximum theoretical disk size of one-third of the Hill radius would be sufficient to allow detection of CO lines. It is therefore feasible to detect their gas disks and constrain the mass of the companion through the kinematic signature. Even in the case of non-detections such observations provide stringent constraints on disk size and gas mass, and this information is crucial for formation theories.
Einsatz der spinalen Navigation in der Wirbelsäulenchirurgie – Kontra
Authors: Halm Henry , Berlin Clara 
Published: February 2019

Zusammenfassung Instrumentierte spinale Fusionen in der Wirbelsäulenchirurgie sind häufig durchgeführte operative Eingriffe bei verschiedensten Pathologien und werden in allen Bereichen der Wirbelsäule angewandt. Das freihändige Setzen von Pedikelschrauben nach Identifikation zuverlässiger, anatomischer Landmarken mit intraoperativer fluoroskopischer Kontrolle ist ein standardisiertes, anerkanntes und in der Literatur vielfach beschriebenes Vorgehen mit relativ geringen Komplikationsraten. Neuere Verfahren ersetzen die freihändige Technik mit Röntgen- oder CT-basierten Navigationssystemen. Diese werden insbesondere von der Industrie als bedeutend risikoärmere und exaktere Verfahren beworben, wobei sie diesen Nachweis bisher schuldig geblieben sind. Ein beispielhafter Vergleich unserer Daten bei Skoliosen, die mit Freihandtechnik instrumentiert wurden, mit Daten von CT-gestützt eingebrachten Pedikelschrauben aus einer anderen Studie belegt eine etwa 10-fach erhöhte Strahlenbelastung in der navigierten Studie, was gerade bei jugendlichen Patienten inakzeptabel ist, zumal in der Freihandtechnik in keinem einzigen Fall eine schraubenassoziierte Komplikation auftrat und auch in den letzten 8 Jahren bei insgesamt 472 Skoliosen nicht aufgetreten ist. Auch sind die Sachkosten und der Zeitaufwand bei Navigation unverhältnismäßig höher. Entscheidend für ein optimales Outcome bei der Freihandtechnik ist eine exzellente Ausbildung der Wirbelsäulenchirurgen mit exakter Kenntnis der Anatomie bzw. Pathoanatomie.