bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic effect of basic fibroblast growth factor (bFGF) and epidermal growth factor on derivation of camel (Camelus dromedarius) trophoblast stem cells
Authors: Alzahrani Faisal A.
Published: June 2019

This study aimed to optimize the derivation of trophectoderm from in vitro-produced camel embryos under feeder-free culture conditions using the basement membrane matrix Matrigel. Trophoblastic vesicles were obtained through mechanical microdissection of in vitro-produced camel (Camelus dromedarius) embryos. Supplementing the culture medium with 10 ng/ml of epidermal growth factor and 10 ng/ml fibroblast growth factor improved the attachment and subsequent outgrowths of cultured trophoblastic vesicles when compared with the control group and the groups supplemented individually with each growth factor. The expression levels of pluripotency genes octamer-binding transcription factor 4 (Oct4), sex determining region Y-box 2 (Sox2), myelocytomatosis proto-oncogene (c-Myc) and anti-apoptotic gene B-cell lymphoma 2 (Bcl2) were increased in trophoblastic vesicles supplemented with both growth factors when compared with the control group. Conversely, both growth factors decreased the expression of apoptotic genes tumour protein p53 (p53) and Bcl-2-associated X protein (Bax). To the best of our knowledge, this may be the first report describing the derivation of trophoblast stem cells from in vitro-produced camel embryos.
Effect of anaemia on the diagnosis of rheumatic heart disease using World Heart Federation criteria
Authors: Klein Jennifer H. , Beaton Andrea , Tompsett Alison , Wiggs Justin , Sable Craig
Published: June 2019

Background:

There is overlap between pathological mitral regurgitation seen in borderline rheumatic heart disease using World Heart Federation echocardiography criteria and physiologic regurgitation found in normal children. One possible contributing factor is higher rates of anaemia in endemic countries.

Objective:

To investigate the contribution of anaemia as a potential confounder in the diagnosis of rheumatic heart disease detected in echocardiographic screening.

Method/Design:

A novel Server 2012 data warehouse tool was used to incorporate haematology and echocardiography databases. The study included a convenience sample of patients from 5 to 18 years old without structural or functional heart disease that had a haemoglobin value within 1 month prior to an echocardiogram. Echocardiogram images were reviewed to determine presence or absence of World Heart Federation criteria for rheumatic heart disease. The rate of rheumatic heart disease among anaemic and non-anaemic children according to gender- and age-based norms groups was compared.

Results:

Of the 935 patients who met the study inclusion criteria, 406 were classified as anaemic. There was no difference in the rate of echocardiograms meeting criteria for borderline rheumatic heart disease in anaemic (2.0%, 95% CI 0.6–3.3%) and non-anaemic children (1.3%, 95% CI 0.3–2.3%). However, there was a statistically significant increase in rates of mitral regurgitation of unclear significance among anaemic versus non-anaemic patients (8.6 versus 3.6%; p = 0.0012).

Conclusion:

Anaemia does not increase the likelihood of meeting echocardiographic criteria for borderline rheumatic heart disease. Future studies should evaluate for the correlation between anaemia and mitral regurgitation in endemic settings.
Evaluation of long-term cardiac side effects of anthracycline chemotherapy by conventional and non-conventional echocardiographic methods in childhood cancer survivors
Authors: Yoldaş Tamer , Yeşil Şule , Karademir Selmin , Şahin Gürses , Arman Örün Utku , Doğan Vehbi , Özgür Senem
Published: June 2019

Objective:

Anthracycline chemotherapeutic agents carry the well-recognised risk of cardiac toxicity. The aim of this study was to determine the long-term effect of anthracycline chemotherapy on the biventricular function in childhood cancer survivors using tissue Doppler imaging and two-dimensional speckle tracking echocardiography.

Patients and Methods:

The study included 45 survivors of childhood cancers and 50 healthy age-matched control patients. Cardiac function was prospectively studied with conventional echocardiography, tissue Doppler imaging, and speckle tracking echocardiography after completion of treatment. The same analysis was performed on matched controls.

Results:

There was no difference in age, gender, height, and weight between the study and control groups. The mean anthracycline dose was 240 ± 106 mg/m2 and the mean remission duration was 8.2 ± 5 years (1–20 years) in the study group. Conventional echocardiography showed similar ejection fraction, shortening fraction, and left ventricle end-diastolic diameter in both groups. Mitral lateral and septal tissue Doppler imaging showed normal but according to control group relatively sub-normal systolic and diastolic function in patient group. The global longitudinal and circumferential strain and strain rates were significantly lower in the patient group compared to control group. Correlation analysis revealed a negative and significant correlation between total anthracycline dose and global longitudinal and circumferential strain and strain rates.

Conclusion:

Sub-clinical systolic and diastolic dysfunction may not be detected by conventional echocardiographic methods which are frequently used in daily practice. Sub-clinical systolic and diastolic dysfunction may be detected more sensitively by echocardiographic method such as speckle tracking echocardiography in childhood cancer survivors.
A word of caution: diabolic behaviour of AndraStents®: inflation of supporting balloon leads to “diabolo”-misconfiguration of the stent
Authors: Happel Christoph M. , Zunzunegui Martínez Jose L. , del Cerro María Jesús , Schranz Dietmar , Khalil Markus , Ballesteros Fernando , Pardeiro César Abelleira , Bertram Harald , Beerbaum Philipp , Haas Nikolaus A.
Published: June 2019

Aims:

Transcatheter implantation of pulmonary balloon-expandable stent-valves requires pre-stenting of the right ventricular outflow tract with large calibre stents. To increase awareness of the associated risks of this part of transcatheter pulmonary valve replacement therapy, we report potential fatal complications during the implantation of AndraStents® in the right ventricular outflow tract in six cases from five different European institutions and their management.

Method and result:

We present a retrospective case series analysis looking at the time period from 2013 to 2018. Of 127 AndraStents® implanted in the right ventricular outflow tract, in six patients, age from 13 to 71 years, a misconfiguration of the AndraStent® occurred forming a “diabolo”-configuration. During inflation of the balloon, the stent showed extreme “dog-boning”, an expansion of the stent at both ends with the middle part remaining unexpanded. This led to rupture of the balloon and loss of manoeuvrability in four patients. Out of the total six cases, in four patients the stent was eventually expanded with high-pressure balloons, and in one case the stent was surgically retrieved. In one patient, in whom a percutaneous retrieval of the embolised stent was attempted, a fatal bleeding occurred.

Conclusions:

Pre-stenting of the right ventricular outflow tract by AndraStents® can lead to misconfiguration of the stent with potentially fatal complications. Rescue strategies of misconfigured stents include stent inflation and placement with high pressure non-compliant balloons or surgical backup. Interventional retrieval measures of AndraStents® cannot be advised.
The Consequences of Quotas: Assessing the Effect of Varied Gender Quotas on Legislator Experience in the European Parliament
Authors: Aldrich Andrea S. , Daniel William T.
Published: June 2019

This article explores the consequences of quotas on the level of diversity observed in legislators’ professional and political experience. We examine how party system and electoral system features that are meant to favor female representation, such as gender quotas for candidate selection or placement mandates on electoral lists, affect the composition of legislatures by altering the mix of professional and political qualifications held by its members. Using data collected for all legislators initially seated to the current session of the European Parliament, one of the largest and most diverse democratically elected legislatures in the world, we find that quotas eliminate gendered differences in experience within the institution, particularly when used in conjunction with placement mandates that ensure female candidates are featured on electoral lists in viable positions. Electoral institutions can generally help to “level the playing field” between the backgrounds of men and women in elected office while increasing the presence of desirable qualities among European Parliament representatives of both genders.
Fairness, accountability and transparency:
notes on algorithmic decision-making in criminal
justice
Authors: Chiao Vincent
Published: June 2019

Over the last few years, legal scholars, policy-makers,
activists and others have generated a vast and
rapidly expanding literature concerning the ethical
ramifications of using artificial intelligence,
machine learning, big data and predictive software
in criminal justice contexts. These concerns can be
clustered under the headings of fairness,
accountability and transparency. First, can we trust
technology to be fair, especially given that the
data on which the technology is based are biased in
various ways? Second, whom can we blame if the
technology goes wrong, as it inevitably will on
occasion? Finally, does it matter if we do not know
how an algorithm works or, relatedly, cannot
understand how it reached its decision? I argue
that, while these are serious concerns, they are not
irresolvable. More importantly, the very same
concerns of fairness, accountability and
transparency apply, with even greater urgency, to
existing modes of decision-making in criminal
justice. The question, hence, is comparative: can
algorithmic modes of decision-making improve upon
the status quo in criminal justice? There is
unlikely to be a categorical answer to this
question, although there are some reasons for
cautious optimism.
Policing the smart city
Authors: Joh Elizabeth E.
Published: June 2019

What will be the consequences for policing as cities become increasingly ‘smarter’? The emerging questions about policing and the smart city have thus far focused primarily on the increased surveillance capacity that a highly networked urban setting provides for law enforcement. More cameras and sensors will mean more watching and less freedom from being watched. The perception of ubiquitous government surveillance might quell dissent and inhibit free expression. As a result, concerns about policing and the smart city echo other responses to surveillance technologies. This essay proposes a different analysis: as cities become ‘smarter’, they increasingly embed policing itself into the urban infrastructure. Policing is inherent to the smart city.
Regulating terrorist content on social media: automation and the rule of law
Authors: Macdonald Stuart , Correia Sara Giro , Watkin Amy-Louise
Published: June 2019

Social-media companies make extensive use of artificial intelligence in their efforts to remove and block terrorist content from their platforms. This paper begins by arguing that, since such efforts amount to an attempt to channel human conduct, they should be regarded as a form of regulation that is subject to rule-of-law principles. The paper then discusses three sets of rule-of-law issues. The first set concerns enforceability. Here, the paper highlights the displacement effects that have resulted from the automated removal and blocking of terrorist content and argues that regard must be had to the whole social-media ecology, as well as to jihadist groups other than the so-called Islamic State and other forms of violent extremism. Since rulebylaw is only a necessary, and not a sufficient, condition for compliance with rule-of-law values, the paper then goes on to examine two further sets of issues: the clarity with which social-media companies define terrorist content and the adequacy of the processes by which a user may appeal against an account suspension or the blocking or removal of content. The paper concludes by identifying a range of research questions that emerge from the discussion and that together form a promising and timely research agenda to which legal scholarship has much to contribute.
Characteristics of Satellite Sampling Errors in Total Precipitable Water from SSMIS, HIRS, and COSMIC Observations
Authors: Xue Yunheng , Li Jun , Menzel W. Paul , Borbas Eva , Ho Shu‐Peng , Li Zhenglong , Li Jinlong
Published: June 2019

This study quantifies the characteristics of different satellite sampling errors in the time series of total precipitable water (TPW) derived from Constellation System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation, Special Sensor Microwave Imager Sounder (SSMIS), and High‐resolution Infrared Radiation Sounder (HIRS) during the overlapping time period of January 2007 to December 2013. Gap‐free data from ERA5 reanalysis of the European Centre for Medium Range Weather Forecasts are used as reference values. All TPW data are first compared with microwave radiometer measurements from Atmospheric Radiation Measurement Program. In general, they are consistent, with all their regression coefficients being greater than 0.77. Discrepancies in global TPW time series can be mainly attributed to the inherent sampling errors of these three different satellite remote sensing systems. COSMIC has small sampling errors in higher latitudes. But it has scarce samples in tropical regions, which leads to a large sampling error of 3.00 mm in the estimation of global TPW. Sampling in SSMIS is more uniform with mean errors less than 0.5 mm. But the sampling is only over the ocean. Sampling errors in HIRS are larger in tropics and north subtropical areas due to clear sky biased sampling. Moreover, it is significantly correlated with the variability of TPW, whereas the sampling error in COSMIC is less influenced by TPW. Sampling errors will be reduced and more consistent global TPW time series will be derived by simply combining the multisensor samplings together.
Solar‐Related Variations of the Cloud Top Circulation Above Aphrodite Terra From VMC/Venus Express Wind Fields
Authors: Patsaeva M. V. , Khatuntsev I. V. , Zasova L. V. , Hauchecorne A. , Titov D. V. , Bertaux J.‐L.
Published: June 2019

Winds derived by a digital tracking technique from ultraviolet (365 nm) images captured by the Venus Monitoring Camera (VMC) onboard the Venus Express spacecraft from 2006 to 2013 were used to study the atmospheric circulation at cloud top level (70 ± 2 km). This data set allows variations of the wind speed with both latitude and longitude to be studied and establishes their correlation with surface topography as well as local time dependence. Both zonal and meridional wind components show some correlation with topography. The minimum zonal wind speed was found at noon above Ovda Regio (10°S, 93°E), the highest region of Aphrodite Terra, one of the largest highlands in the equatorial region. The area of slow zonal wind extends to at least 30°S and shifts in the direction of superrotation in the afternoon and with increasing latitude (poleward). The observed deceleration of cloud top wind was recently attributed to the interaction of the gravity (mountain) waves generated by Aphrodite Terra with the atmospheric circulation. The present study was performed for different local time over the mountainous longitudes. The deceleration pattern in the zonal wind field is mainly conserved within a few hours around noon. Systematic longitude shift is observed in the afternoon in the direction of the evening terminator. Another area of perturbation of both zonal and meridional wind components is observed in the equatorial region around LT = 13–14 hr and may be explained by the solar tide.
Ion Heating by Electromagnetic Ion Cyclotron Waves and Magnetosonic Waves in the Earth's Inner Magnetosphere
Authors: Ma Q. , Li W. , Yue C. , Thorne R. M. , Bortnik J. , Kletzing C. A. , Kurth W. S. , Hospodarsky G. B. , Reeves G. D. , Spence H. E.
Published: June 2019

Electromagnetic ion cyclotron (EMIC) waves and magnetosonic waves are commonly observed in the Earth's magnetosphere associated with enhanced ring current activity. Using wave and ion measurements from the Van Allen Probes, we identify clear correlations between the hydrogen‐ and helium‐band EMIC waves with the enhancement of trapped helium and oxygen ion fluxes, respectively. We calculate the diffusion coefficients of different ion species using quasi‐linear theory to understand the effects of resonant scattering by EMIC waves. Our calculations indicate that EMIC waves can cause pitch angle scattering loss of several keV to hundreds of keV ions, and heating of tens of eV to several keV helium and oxygen ions by hydrogen‐ and helium‐band EMIC waves, respectively. Moreover, we found that magnetosonic waves can cause the resonant heating of thermal protons. Our study indicates the importance of energy transfer from the EMIC and magnetosonic waves to ions with different species at thermal energies.
Saturation Properties of Whistler Wave Instability in a Plasma With Two Electron Components
Authors: Wu Yifan , Tao Xin , Lu Quanming , Wang Shui
Published: June 2019

Saturation properties of whistler wave instability driven by electron temperature anisotropy in a plasma with two electron components are investigated using particle‐in‐cell (PIC) simulations. Most of the previous self‐consistent PIC simulations or quasi‐linear theory used a single bi‐Maxwellian distribution of electrons, which might apply to solar wind or magnetosheath. In the inner magnetosphere, however, there is frequently a cold and dense electron component, coexisting with a hot electron component. In this work, we investigate the relation between temperature anisotropy (A) and parallel plasma beta (β‖) at saturation. Our results agree well with the previous conclusion obtained from linear theory in most cases. However, We show that the inverse relation breaks when β‖ is larger than certain value
, beyond which A increases with increasing β‖. We also investigated the dependence of the saturation wave intensity on plasma beta and the initial linear growth rate and show that the saturation amplitude can be modeled as a function of the maximum initial linear growth rate even in a plasma with two electron components. Our results might be useful to couple the microscopic wave excitation process with macroscopic global energetic electron dynamics and to understand whistler wave excitation in the inner magnetosphere.
Paleomagnetic Evidence for a Partially Differentiated Ordinary Chondrite Parent Asteroid
Authors: Bryson J. F. J. , Weiss B. P. , Getzin B. , Abrahams J. N. H. , Nimmo F. , Scholl A.
Published: June 2019

The textures and accretion ages of chondrites have been used to argue that their parent asteroids never differentiated. Without a core, undifferentiated planetesimals could not have generated magnetic fields through dynamo activity, so chondrites are not expected to have experienced such fields. However, the magnetic remanence carried by the CV chondrites is consistent with dynamo‐generated fields, hinting that partially differentiated asteroids consisting of an unmelted crust atop a differentiated interior may exist. Here, we test this hypothesis by applying synchrotron X‐ray microscopy to metallic veins in the slowly cooled H6 chondrite Portales Valley. The magnetic remanence carried by nanostructures in these veins indicates that this meteorite recorded a magnetic field over a period of tens to hundreds of years at ∼100 Myr after solar system formation. These properties are inconsistent with external field sources such as the nebula, solar wind, or impacts, but are consistent with dynamo‐generated fields, indicating that the H chondrite parent body contained an advecting metallic core and was therefore partially differentiated. We calculate the thermal evolution of the chondritic portions of partially differentiated asteroids that form through incremental accretion across 105 to 106 years, finding this can agree with the measured ages and cooling rates of multiple H chondrites. We also predict that the cores of these bodies could have been partially liquid and feasibly generating a dynamo at 100 Myr after solar system formation. These observations contribute to a growing body of evidence supporting a spectrum of internal differentiation within some asteroids with primitive surfaces.
Assessment and Reduction of the Physical Parameterization Uncertainty for Noah‐MP Land Surface Model
Authors: Gan Yanjun , Liang Xin‐Zhong , Duan Qingyun , Chen Fei , Li Jianduo , Zhang Yu
Published: June 2019

The community Noah land surface model with multiparameterization options (Noah‐MP) provides a plethora of model configurations with varying complexity for land surface modeling. The practical application of this model requires a basic understanding of the relative abilities of its various parameterization configurations in representing spatiotemporal variability and hydrologic connectivity. We designed an ensemble of 288 experiments from multiparameterization schemes of six physical processes to assess and reduce the structural uncertainty for land surface modeling over 10 hydrologic regions in China for the period 2001–2010. The observed latent heat (LH) was well reproduced by the ensemble. Meanwhile, most experiments underestimated sensible heat (SH) throughout the year and overestimated the cold season but underestimated the warm season terrestrial water storage anomaly (TWSA). The sensitive processes and best‐performing schemes varied not only with regions but also among variables. The LH and SH were most sensitive to runoff‐groundwater (RUN), surface heat exchange coefficient (SFC), and radiation transfer (RAD). The TWSA was dominated by RUN and RAD while largely influenced by soil moisture factor for stomatal resistance (BTR) and frozen soil permeability (INF) over some limited regions. By contrast, supercooled liquid water (FRZ) had little influence on all variables. Our optimization for individual variables produced high mean Taylor skill scores that ranged from 0.95–0.99 for LH, 0.82–0.99 for SH, and 0.63–0.95 for TWSA depending on regions. The simultaneous optimization made trade‐off among the three variables, which improved TWSA performance at the cost of reducing the skill for LH and SH over a few regions.
Perceptions of Clinical Training in Biopsychosocial Treatment of Pediatric Functional Abdominal Pain: A Survey of Medical Students
Authors: Wojtowicz Andrea A. , Schurman Jennifer Verrill , Cushing Christopher C. , Plevinsky Jill M. , Greenley Rachel Neff
Published: June 2019

Objective: The Institute of Medicine has called for greater integration of behavioral sciences in health care. Examining medical students’ exposure to and perceptions of a biopsychosocial approach to treating pediatric functional gastrointestinal disorders associated with pain (FGIDs-AP) may identify roles for pediatric psychologists. This study examined medical students’ educational and clinical experiences with an interprofessional approach to conceptualizing and treating FGIDs-AP, barriers to interprofessional collaboration, and perceptions of the value of interprofessional collaboration. Methods: Seventy-two students from a Midwestern medical school who completed a pediatric medicine rotation participated. Participants provided demographic and training information and completed the Readiness for Interprofessional Learning Scale and the Pediatric Recurrent Abdominal Pain Practice Survey: Student Version via online survey. The latter assessed didactic and training experiences in the biopsychosocial conceptualization of pediatric FGIDs-AP; clinical assessment and treatment practices for these conditions; and perceived barriers to interprofessional collaboration. Results: Although 71% of participants received education in the biopsychosocial model of pediatric FGIDs-AP, only 21% applied the model clinically and only 3% indicated regularly collaborating with psychologists. Barriers to interprofessional collaboration included time limitations, lack of family interest in psychology involvement, and limited access to psychologists. Participants with more favorable attitudes toward interprofessionalism rated collaboration as more helpful. Conclusions: Pediatric psychologists are uniquely qualified to provide training in the application of the biopsychosocial model in the treatment of pediatric FGIDs-AP and other conditions. Ongoing efforts to involve pediatric psychologists in medical student training could improve implementation of interprofessional care and enhance patient outcomes.

Implications for Impact Statement

Medical students and residents would benefit from greater exposure to the biopsychosocial conceptualization of pediatric functional abdominal pain in the classroom. In addition, more opportunities to engage in collaborative care with behavioral health providers in treating patients with pediatric functional abdominal pain are warranted. Addressing barriers to interprofessional education and clinical training as well barriers to implementing interprofessional care for pediatric abdominal pain may improve medical students’ perceptions of this model of care, thereby increasing its implementation and ultimately improving patient outcomes.
Adrenomedullin alleviates the pyroptosis of Leydig cells by promoting autophagy via the ROS–AMPK–mTOR axis
Authors: Li Ming-yong , Zhu Xia-lian , Zhao Bi-xia , Shi Lei , Wang Wei , Hu Wei , Qin Song-lin , Chen Bing-hai , Zhou Pang-hu , Qiu Bo , Gao Yong , Liu Bo-long
Published: June 2019

Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells exposed to lipopolysaccharide (LPS) by promoting autophagy. Primary rat Leydig cells were treated with various concentrations of LPS and ADM, together with or without N-acetyl-L-cysteine (NAC) or 3-methyladenine (3-MA). Cell proliferation was detected through CCK-8 and BrdU incorporation assays, and ROS level was measured with the DCFDA assay. Real-time PCR, western blot, immunofluorescence, transmission electron microscopy, TUNEL and flow cytometry were performed to examine ADM’s effect on the pyroptosis, autophagy and steroidogenic enzymes of Leydig cells and AMPK/mTOR signalling. Like NAC, ADM dose-dependently reduced LPS-induced cytotoxicity and ROS overproduction. ADM also dose-dependently ameliorated LPS-induced pyroptosis by reversing the increased expression of NLRP3, ASC, caspase-1, IL-1β, IL-18, GSDMD, caspase-3, caspase-7, TUNEL-positive and PI and active caspase-1 double-stained positive rate, DNA fragmentation and LDH concentration, which could be rescued via co-incubation with 3-MA. ADM dose-dependently increased autophagy in LPS-induced Leydig cells, as confirmed by the increased expression of LC3-I/II, Beclin-1 and ATG-5; decreased expression of p62 and autophagosomes formation; and increased LC3-II/LC3-I ratio. However, co-treatment with 3-MA evidently decreased autophagy. Furthermore, ADM dose-dependently rescued the expression of steroidogenic enzymes, including StAR, P450scc, 3β-HSD and CYP17, and testosterone production in LPS-induced Leydig cells. Like rapamycin, ADM dose-dependently enhanced AMPK phosphorylation but reduced mTOR phosphorylation in LPS-induced Leydig cells, which could be rescued via co-incubation with 3-MA. In addition, pyroptosis was further decreased, and autophagy was further promoted in LPS-induced Leydig cells upon co-treatment with ADM and rapamycin. ADM may protect the steroidogenic functions of Leydig cells against pyroptosis by activating autophagy via the ROS–AMPK–mTOR axis.
FOXF2 reprograms breast cancer cells into bone metastasis seeds
Authors: Wang Shuo , Li Gui-Xi , Tan Cong-Cong , He Rui , Kang Li-Juan , Lu Jun-Tao , Li Xiao-Qing , Wang Qing-Shan , Liu Pei-Fang , Zhai Qiong-Li , Feng Yu-Mei
Published: June 2019

Bone metastases occur in most advanced breast cancer patients and cause serious skeletal-related complications. The mechanisms by which bone metastasis seeds develop in primary tumors and specifically colonize the bone remain to be elucidated. Here, we show that forkhead box F2 (FOXF2) functions as a master transcription factor for reprogramming cancer cells into an osteomimetic phenotype by pleiotropic transactivation of the BMP4/SMAD1 signaling pathway and bone-related genes that are expressed at early stages of bone differentiation. The epithelial-to-osteomimicry transition regulated by FOXF2 confers a tendency on cancer cells to metastasize to bone which leads to osteolytic bone lesions. The BMP antagonist Noggin significantly inhibits FOXF2-driven osteolytic bone metastasis of breast cancer cells. Thus, targeting the FOXF2-BMP/SMAD axis might be a promising therapeutic strategy to manage bone metastasis. The role of FOXF2 in transactivating bone-related genes implies a biological function of FOXF2 in regulating bone development and remodeling.
Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption
Authors: Villanueva Jesús E. , Livelo Christopher , Trujillo Adriana S. , Chandran Sahaana , Woodworth Brendon , Andrade Leo , Le Hiep D. , Manor Uri , Panda Satchidananda , Melkani Girish C.
Published: June 2019

Pathological obesity can result from genetic predisposition, obesogenic diet, and circadian rhythm disruption. Obesity compromises function of muscle, which accounts for a majority of body mass. Behavioral intervention that can counteract obesity arising from genetic, diet or circadian disruption and can improve muscle function holds untapped potential to combat the obesity epidemic. Here we show thatDrosophila melanogaster(fruit fly) subject to obesogenic challenges exhibits metabolic disease phenotypes in skeletal muscle; sarcomere disorganization, mitochondrial deformation, upregulation of Phospho-AKT level, aberrant intramuscular lipid infiltration, and insulin resistance. Imposing time-restricted feeding (TRF) paradigm in which flies were fed for 12 h during the day counteracts obesity-induced dysmetabolism and improves muscle performance by suppressing intramuscular fat deposits, Phospho-AKT level, mitochondrial aberrations, and markers of insulin resistance. Importantly, TRF was effective even in an irregular lighting schedule mimicking shiftwork. Hence, TRF is an effective dietary intervention for combating metabolic dysfunction arising from multiple causes.
A striatal interneuron circuit for continuous target pursuit
Authors: Kim Namsoo , Li Haofang E. , Hughes Ryan N. , Watson Glenn D. R. , Gallegos David , West Anne E. , Kim Il Hwan , Yin Henry H.
Published: June 2019

Most adaptive behaviors require precise tracking of targets in space. In pursuit behavior with a moving target, mice use distance to target to guide their own movement continuously. Here, we show that in the sensorimotor striatum, parvalbumin-positive fast-spiking interneurons (FSIs) can represent the distance between self and target during pursuit behavior, while striatal projection neurons (SPNs), which receive FSI projections, can represent self-velocity. FSIs are shown to regulate velocity-related SPN activity during pursuit, so that movement velocity is continuously modulated by distance to target. Moreover, bidirectional manipulation of FSI activity can selectively disrupt performance by increasing or decreasing the self-target distance. Our results reveal a key role of the FSI-SPN interneuron circuit in pursuit behavior and elucidate how this circuit implements distance to velocity transformation required for the critical underlying computation.
Innovative mouse model mimicking human-like features of spinal cord injury: efficacy of Docosahexaenoic acid on acute and chronic phases
Authors: Marinelli Sara , Vacca Valentina , De Angelis Federica , Pieroni Luisa , Orsini Tiziana , Parisi Chiara , Soligo Marzia , Protto Virginia , Manni Luigi , Guerrieri Roberto , Pavone Flaminia
Published: June 2019

Traumatic spinal cord injury has dramatic consequences and a huge social impact. We propose a new mouse model of spinal trauma that induces a complete paralysis of hindlimbs, still observable 30 days after injury. The contusion, performed without laminectomy and deriving from the pressure exerted directly on the bone, mimics more closely many features of spinal injury in humans. Spinal cord was injured at thoracic level 10 (T10) in adult anesthetized female CD1 mice, mounted on stereotaxic apparatus and connected to a precision impactor device. Following severe injury, we evaluated motor and sensory functions, and histological/morphological features of spinal tissue at different time points. Moreover, we studied the effects of early and subchronic administration of Docosahexaenoic acid, investigating functional responses, structural changes proximal and distal to the lesion in primary and secondary injury phases, proteome modulation in injured spinal cord. Docosahexaenoic acid was able i) to restore behavioural responses and ii) to induce pro-regenerative effects and neuroprotective action against demyelination, apoptosis and neuroinflammation. Considering the urgent health challenge represented by spinal injury, this new and reliable mouse model together with the positive effects of docosahexaenoic acid provide important translational implications for promising therapeutic approaches for spinal cord injuries.
Myofibroblast modulation of cardiac myocyte structure and function
Authors: Nagaraju Chandan K. , Dries Eef , Gilbert Guillaume , Abdesselem Mouna , Wang Nan , Amoni Matthew , Driesen Ronald B. , Sipido Karin R.
Published: June 2019

After myocardial infarction, resident fibroblasts (Fb) differentiate towards myofibroblasts (MyoFb), generating the scar tissue and the interstitial fibrosis seen in the adjacent myocardium. Fb and MyoFb have the potential to interact with cardiac myocytes (CMs) but insight into the phenotype-specific role and mode of interaction is still incomplete. Our objectives are to further define the modulation of CMs by MyoFbs compared to Fbs, as well as the role of direct contact through gap junctions vs. soluble mediators, using Fbs and CMs from pig left ventricle. Fbs were treated to maintain an undifferentiated state (SD-208) or to attain full differentiation to MyoFb (TGF-β1). Fbs and MyoFbs were co-cultured with CMs, with the possibility of direct contact or separated by a Thincert membrane. Only in direct co-culture, both Fbs and MyoFbs were able to decrease CM viability after 2 days. Only MyoFbs induced significant distal spreading of CMs in both direct and indirect co-culture. MyoFbs, but not Fbs, readily made connections with CMs in direct co-culture and connexin 43 expression in MyoFb was higher than in Fb. When coupled to CMs, MyoFbs reduced the CM action potential duration and hyperpolarized the CM resting membrane potential. Uncoupling reversed these effects. In conclusion, MyoFbs, but not Fbs, alter the CM structural phenotype. MyoFbs, but not Fbs, are likely to electrically connect to CMs and thereby modulate the CM membrane potential. These data provide further support for an active role of MyoFbs in the arrhythmogenic substrate after cardiac remodelling.
High-density Mapping Guided Pulmonary Vein Isolation for Treatment of Atrial Fibrillation - Two-year clinical outcome of a single center experience
Authors: Siebermair J. , Neumann B. , Risch F. , Riesinger L. , Vonderlin N. , Koehler M. , Lackermaier K. , Fichtner S. , Rizas K. , Sattler S. M. , Sinner M. F. , Kääb S. , Estner H. L. , Wakili R.
Published: June 2019

Pulmonary vein isolation (PVI) as interventional treatment for atrial fibrillation (AF) aims to eliminate arrhythmogenic triggers from the PVs. Improved signal detection facilitating a more robust electrical isolation might be associated with a better outcome. This retrospective cohort study compared PVI procedures using a novel high-density mapping system (HDM) with improved signal detection vs. age- and sex-matched PVIs using a conventional 3D mapping system (COM). Endpoints comprised freedom from AF and procedural parameters. In total, 108 patients (mean age 63.9 ± 11.2 years, 56.5% male, 50.9% paroxysmal AF) were included (n = 54 patients/group). Our analysis revealed that HDM was not superior regarding freedom from AF (mean follow-up of 494.7 ± 26.2 days), with one- and two-year AF recurrence rates of 38.9%/46.5% (HDM) and 38.9%/42.2% (COM), respectively. HDM was associated with reduction in fluoroscopy times (18.8 ± 10.6 vs. 29.8 ± 13.4 min; p < 0.01) and total radiation dose (866.0 ± 1003.3 vs. 1731.2 ± 1978.4 cGy; p < 0.01) compared to the COM group. HDM was equivalent but not superior to COM with respect to clinical outcome after PVI and resulted in reduced fluoroscopy time and radiation exposure. These results suggest that HDM-guided PVI is effective and safe for AF ablation. Potential benefits in comparison to conventional mapping systems, e.g. arrhythmia recurrence rates, have to be addressed in randomized trials.
Eukaryotic and cyanobacterial communities associated with marine snow particles in the oligotrophic Sargasso Sea
Authors: Lundgreen Regitze B. C. , Jaspers Cornelia , Traving Sachia J. , Ayala Daniel J. , Lombard Fabien , Grossart Hans-Peter , Nielsen Torkel G. , Munk Peter , Riemann Lasse
Published: June 2019

Marine snow aggregates represent heterogeneous agglomerates of dead and living organic matter. Composition is decisive for their sinking rates, and thereby for carbon flux to the deep sea. For oligotrophic oceans, information on aggregate composition is particularly sparse. To address this, the taxonomic composition of aggregates collected from the subtropical and oligotrophic Sargasso Sea (Atlantic Ocean) was characterized by 16S and 18S rRNA gene sequencing. Taxonomy assignment was aided by a collection of the contemporary plankton community consisting of 75 morphologically and genetically identified plankton specimens. The diverse rRNA gene reads of marine snow aggregates, not considering Trichodesmium puffs, were dominated by copepods (52%), cnidarians (21%), radiolarians (11%), and alveolates (8%), with sporadic contributions by cyanobacteria, suggesting a different aggregate composition than in eutrophic regions. Composition linked significantly with sampling location but not to any measured environmental parameters or plankton biomass composition. Nevertheless, indicator and network analyses identified key roles of a few rare taxa. This points to complex regulation of aggregate composition, conceivably affected by the environment and plankton characteristics. The extent to which this has implications for particle densities, and consequently for sinking rates and carbon sequestration in oligotrophic waters, needs further interrogation.
Description of strongly heat-inducible heat shock protein 70 transcripts from Baikal endemic amphipods
Authors: Drozdova Polina , Bedulina Daria , Madyarova Ekaterina , Rivarola-Duarte Lorena , Schreiber Stephan , Stadler Peter F. , Luckenbach Till , Timofeyev Maxim
Published: June 2019

Heat shock proteins/cognates 70 are chaperones essential for proper protein folding. This protein family comprises inducible members (Hsp70s) with expression triggered by the increased concentration of misfolded proteins due to protein-destabilizing conditions, as well as constitutively expressed cognate members (Hsc70s). Previous works on non-model amphipod species Eulimnogammarus verrucosus and Eulimnogammarus cyaneus, both endemic to Lake Baikal in Eastern Siberia, have only revealed a constitutively expressed form, expression of which was moderately further induced by protein-destabilizing conditions. Here we describe heat-inducible hsp70s in these species. Contrary to the common approach of using sequence similarity with hsp/hsc70 of a wide spectrum of organisms and some characteristic features, such as absence of introns within genes and presence of heat shock elements in their promoter areas, the present study is based on next-generation sequencing for the studied or related species followed by differential expression analysis, quantitative PCR validation and detailed investigation of the predicted polypeptide sequences. This approach allowed us to describe a novel type of hsp70 transcripts that overexpress in response to heat shock. Moreover, we propose diagnostic sequence features of this Hsp70 type for amphipods. Phylogenetic comparisons with different types of Hsp/Hsc70s allowed us to suggest that the hsp/hsc70 gene family in Amphipoda diversified into cognate and heat-inducible paralogs independently from other crustaceans. Thus, the cognate and inducible hsp70 types in distant taxa may not be recognized by sequence similarity.
Evaluation of six blood-based age prediction models using DNA methylation analysis by pyrosequencing
Authors: Daunay Antoine , Baudrin Laura G. , Deleuze Jean-François , How-Kit Alexandre
Published: June 2019

DNA methylation has been identified as the most promising molecular biomarker for the prediction of age. Several DNA methylation-based models have been proposed for age prediction based on blood samples, using mainly pyrosequencing. These methods present different performances for age prediction and have rarely, if ever, been evaluated and intercompared in an independent validation study. Here, for the first time, we evaluate and compare six blood-based age prediction models (Bekaert1, Park2, Thong3, Weidner4, and the Zbiec-Piekarska 15 and Zbiec-Piekarska 26), using DNA methylation analysis by pyrosequencing on 100 blood samples from French individuals aged between 19–65 years. For each model, we perform correlation analysis and evaluate age-prediction performance (mean absolute deviation (MAD) and standard error of the estimate (SEE)). The best age-prediction performances were found with the Bekaert and Thong models (MAD of 4.5–5.2, SEE of 6.8–7.2), followed by the Zbiec-Piekarska 1 model (MAD of 6.8 and SEE of 9.2), while the Park, Weidner and Zbiec-Piekarska 2 models presented lower performances (MAD of 7.2–8.7 and SEE of 9.2–10.3). Given these results, we recommend performing systematic, independent evaluation of all age prediction models on a same cohort to validate the different models and compare their performance.
A sensitive and simple targeted proteomics approach to quantify transcription factor and membrane proteins of the unfolded protein response pathway in glioblastoma cells
Authors: Nguyen Chi D. L. , Malchow Sebastian , Reich Stefan , Steltgens Sascha , Shuvaev Konstantin V. , Loroch Stefan , Lorenz Christin , Sickmann Albert , Knobbe-Thomsen Christiane B. , Tews Björn , Medenbach Jan , Ahrends Robert
Published: June 2019

Many cellular events are driven by changes in protein expression, measurable by mass spectrometry or antibody-based assays. However, using conventional technology, the analysis of transcription factor or membrane receptor expression is often limited by an insufficient sensitivity and specificity. To overcome this limitation, we have developed a high-resolution targeted proteomics strategy, which allows quantification down to the lower attomol range in a straightforward way without any prior enrichment or fractionation approaches. The method applies isotope-labeled peptide standards for quantification of the protein of interest. As proof of principle, we applied the improved workflow to proteins of the unfolded protein response (UPR), a signaling pathway of great clinical importance, and could for the first time detect and quantify all major UPR receptors, transducers and effectors that are not readily detectable via antibody-based-, SRM- or conventional PRM assays. As transcription and translation is central to the regulation of UPR, quantification and determination of protein copy numbers in the cell is important for our understanding of the signaling process as well as how pharmacologic modulation of these pathways impacts on the signaling. These questions can be answered using our newly established workflow as exemplified in an experiment using UPR perturbation in a glioblastoma cell lines.
Truels and strategies for survival
Authors: Dorraki Mohsen , Allison Andrew , Abbott Derek
Published: June 2019

The truel is a three person competition that generalises the classic duel. In this game three players try to eliminate each other in a series of one-to-one duels until there is only one survivor. The players’ marksmanship, shooting order and strategies for choosing a target play a significant role in individual’s survival probability. Strategies such as shooting into the air (abstention), shooting at the strongest opponent, and shooting at the weakest opponent have been analysed in the previous literature. In this paper, for the first time, we consider suicidal and random strategies that can be chosen by the weaker player. We show that although there is no possible highest probability region for weakest player adopting suicidal strategy, the player may increase the survival probability via switching between suicidal and abstention strategies randomly. In addition, we demonstrate that there is a narrow survival area for the weakest player when the player aims randomly at two other opponents, and eventually the area fades away if the player fires randomly at himself or the other two opponents.
The 2017–19 activity at Mount Agung in Bali (Indonesia): Intense unrest, monitoring, crisis response, evacuation, and eruption
Authors: Syahbana D. K. , Kasbani K. , Suantika G. , Prambada O. , Andreas A. S. , Saing U. B. , Kunrat S. L. , Andreastuti S. , Martanto M. , Kriswati E. , Suparman Y. , Humaida H. , Ogburn S. , Kelly P. J. , Wellik J. , Wright H. M. N. , Pesicek J. D. , Wessels R. , Kern C. , Lisowski M. , Diefenbach A. , Poland M. , Beauducel F. , Pallister J. , Vaughan R. G. , Lowenstern J. B.
Published: June 2019

After 53 years of quiescence, Mount Agung awoke in August 2017, with intense seismicity, measurable ground deformation, and thermal anomalies in the summit crater. Although the seismic unrest peaked in late September and early October, the volcano did not start erupting until 21 November. The most intense explosive eruptions with accompanying rapid lava effusion occurred between 25 and 29 November. Smaller infrequent explosions and extrusions continue through the present (June 2019). The delay between intense unrest and eruption caused considerable challenges to emergency responders, local and national governmental agencies, and the population of Bali near the volcano, including over 140,000 evacuees. This paper provides an overview of the volcanic activity at Mount Agung from the viewpoint of the volcano observatory and other scientists responding to the volcanic crisis. We discuss the volcanic activity as well as key data streams used to track it. We provide evidence that magma intruded into the mid-crust in early 2017, and again in August of that year, prior to intrusion of an inferred dike between Mount Agung and Batur Caldera that initiated an earthquake swarm in late September. We summarize efforts to forecast the behavior of the volcano, to quantify exclusion zones for evacuations, and to work with emergency responders and other government agencies to make decisions during a complex and tense volcanic crisis.