bluuebunny/crossref_metadata_2025 huggingface dataset:
WISH: wavefront imaging sensor with high resolution
Authors: Wu Yicheng , Sharma Manoj Kumar , Veeraraghavan Ashok
Published: May 2019

Wavefront sensing is the simultaneous measurement of the amplitude and phase of an incoming optical field. Traditional wavefront sensors such as Shack-Hartmann wavefront sensor (SHWFS) suffer from a fundamental tradeoff between spatial resolution and phase estimation and consequently can only achieve a resolution of a few thousand pixels. To break this tradeoff, we present a novel computational-imaging-based technique, namely, the Wavefront Imaging Sensor with High resolution (WISH). We replace the microlens array in SHWFS with a spatial light modulator (SLM) and use a computational phase-retrieval algorithm to recover the incident wavefront. This wavefront sensor can measure highly varying optical fields at more than 10-megapixel resolution with the fine phase estimation. To the best of our knowledge, this resolution is an order of magnitude higher than the current noninterferometric wavefront sensors. To demonstrate the capability of WISH, we present three applications, which cover a wide range of spatial scales. First, we produce the diffraction-limited reconstruction for long-distance imaging by combining WISH with a large-aperture, low-quality Fresnel lens. Second, we show the recovery of high-resolution images of objects that are obscured by scattering. Third, we show that WISH can be used as a microscope without an objective lens. Our study suggests that the designing principle of WISH, which combines optical modulators and computational algorithms to sense high-resolution optical fields, enables improved capabilities in many existing applications while revealing entirely new, hitherto unexplored application areas.
Loss of TET2 and TET3 in regulatory T cells unleashes effector function
Authors: Yue Xiaojing , Lio Chan-Wang J. , Samaniego-Castruita Daniela , Li Xiang , Rao Anjana
Published: May 2019

TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3fl/flFoxp3Cre mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these mice show altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. In littermate mice with severe inflammation, both CD4+Foxp3+ and CD4+Foxp3− cells show strong skewing towards Tfh/Th17 phenotypes. Wild-type Treg cells in mixed bone marrow chimeras and in Tet2/3fl/flFoxp3WT/Cre heterozygous female mice are unable to rescue the aberrant properties of Tet2/3fl/flFoxp3Cre Treg cells. Treg cells from Tet2/3fl/flFoxp3Cre mice tend to lose Foxp3 expression, and transfer of total CD4+ T cells isolated from Tet2/3fl/flFoxp3Cre mice could elicit inflammatory disease in fully immunocompetent mice. Together, these data indicate that Tet2 and Tet3 are guardians of Treg cell stability and immune homeostasis.
Capicua regulates neural stem cell proliferation and lineage specification through control of Ets factors
Authors: Ahmad Shiekh Tanveer , Rogers Alexandra D. , Chen Myra J. , Dixit Rajiv , Adnani Lata , Frankiw Luke S. , Lawn Samuel O. , Blough Michael D. , Alshehri Mana , Wu Wei , Marra Marco A. , Robbins Stephen M. , Cairncross J. Gregory , Schuurmans Carol , Chan Jennifer A.
Published: May 2019

Capicua (Cic) is a transcriptional repressor mutated in the brain cancer oligodendroglioma. Despite its cancer link, little is known of Cic’s function in the brain. We show that nuclear Cic expression is strongest in astrocytes and neurons but weaker in stem cells and oligodendroglial lineage cells. Using a new conditional Cic knockout mouse, we demonstrate that forebrain-specific Cic deletion increases proliferation and self-renewal of neural stem cells. Furthermore, Cic loss biases neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells (OPCs). These proliferation and lineage effects are dependent on de-repression of Ets transcription factors. In patient-derived oligodendroglioma cells, CIC re-expression or ETV5 blockade decreases lineage bias, proliferation, self-renewal, and tumorigenicity. Our results identify Cic as an important regulator of cell fate in neurodevelopment and oligodendroglioma, and suggest that its loss contributes to oligodendroglioma by promoting proliferation and an OPC-like identity via Ets overactivity.
Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders
Authors: Saffouri George B. , Shields-Cutler Robin R. , Chen Jun , Yang Yi , Lekatz Heather R. , Hale Vanessa L. , Cho Janice M. , Battaglioli Eric J. , Bhattarai Yogesh , Thompson Kevin J. , Kalari Krishna K. , Behera Gaurav , Berry Jonathan C. , Peters Stephanie A. , Patel Robin , Schuetz Audrey N. , Faith Jeremiah J. , Camilleri Michael , Sonnenburg Justin L. , Farrugia Gianrico , Swann Jonathan R. , Grover Madhusudan , Knights Dan , Kashyap Purna C.
Published: May 2019

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.
Author Correction: Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation
Authors: Malacaria Eva , Pugliese Giusj Monia , Honda Masayoshi , Marabitti Veronica , Aiello Francesca Antonella , Spies Maria , Franchitto Annapaola , Pichierri Pietro
Published: May 2019

The original version of this Article contained an error in Fig. 2. The immunofluorescence images in panel d were inadvertently replaced with duplicates of those in panel c during final assembly of the figure. This has been corrected in the PDF and HTML versions of the Article.
Nanoscale self-healing mechanisms in shape memory ceramics
Authors: Zhang Ning , Asle Zaeem Mohsen
Published: May 2019

Shape memory ceramics, such as yttria-stabilized tetragonal zirconia (YSTZ), offer unique properties including ultra-high operating temperatures and high resistance to oxidation. However, they are susceptible to formation of defects during manufacturing and/or by mechanical deformation. To completely take advantage of their shape memory properties, it is necessary to fully understand the nano-structural evolution of defects under external stimuli. In this study, defect evolution behaviors in YSTZ nanopillars are investigated by atomistic simulations. Two characteristic orientations of$$\left[ {01\bar 1} \right]$$011¯and [001] are selected to represent the dominant deformation mechanisms of phase transformation and dislocation migration, respectively. Volume expansion associated with the tetragonal to monoclinic phase transformation is observed to promote healing of crack and void. Atom stress analyses reveal stress concentrations along the newly formed monoclinic phase bands. A critical crack width is identified, less than which the crack can be fully closed in compression. For [001]-oriented YSTZ nanopillars, dislocation migration leads to formations of an amorphous phase, which also assist the crack and void closure process. The revealed crack/void healing mechanisms may provide a path for mitigating internal defects that influences the mechanical properties and deformation mechanisms of shape memory ceramics.
Impact of lattice relaxations on phase transitions in a high-entropy alloy studied by machine-learning potentials
Authors: Kostiuchenko Tatiana , Körmann Fritz , Neugebauer Jörg , Shapeev Alexander
Published: May 2019

Recently, high-entropy alloys (HEAs) have attracted wide attention due to their extraordinary materials properties. A main challenge in identifying new HEAs is the lack of efficient approaches for exploring their huge compositional space. Ab initio calculations have emerged as a powerful approach that complements experiment. However, for multicomponent alloys existing approaches suffer from the chemical complexity involved. In this work we propose a method for studying HEAs computationally. Our approach is based on the application of machine-learning potentials based on ab initio data in combination with Monte Carlo simulations. The high efficiency and performance of the approach are demonstrated on the prototype bcc NbMoTaW HEA. The approach is employed to study phase stability, phase transitions, and chemical short-range order. The importance of including local relaxation effects is revealed: they significantly stabilize single-phase formation of bcc NbMoTaW down to room temperature. Finally, a so-far unknown mechanism that drives chemical order due to atomic relaxation at ambient temperatures is discovered.
Recent practical researches in the development of gluten-free breads
Authors: Yano Hiroyuki
Published: May 2019

Wheat bread is consumed globally and has played a critical role in the story of civilization since the development of agriculture. While the aroma and flavor of this staple food continue to delight and satisfy most people, some individuals have a specific allergy to wheat or a genetic disposition to celiac disease. To improve the quality of life of these patients from a dietary standpoint, food-processing researchers have been seeking to develop high-quality gluten-free bread. As the quality of wheat breads depends largely on the viscoelastic properties of gluten, various ingredients have been employed to simulate its effects, such as hydrocolloids, transglutaminase, and proteases. Recent attempts have included the use of redox regulation as well as particle-stabilized foam. In this short review, we introduce the ongoing advancements in the development of gluten-free bread, by our laboratory as well as others, focusing mainly on rice-based breads. The social and scientific contexts of these efforts are also mentioned.
A yield-cost tradeoff governs Escherichia coli’s decision between fermentation and respiration in carbon-limited growth
Authors: Mori Matteo , Marinari Enzo , De Martino Andrea
Published: May 2019

Living cells react to changes in growth conditions by re-shaping their proteome. This accounts for different stress-response strategies, both specific (i.e., aimed at increasing the availability of stress-mitigating proteins) and systemic (such as large-scale changes in the use of metabolic pathways aimed at a more efficient exploitation of resources). Proteome re-allocation can, however, imply significant biosynthetic costs. Whether and how such costs impact the growth performance are largely open problems. Focusing on carbon-limited E. coli growth, we integrate genome-scale modeling and proteomic data to address these questions at quantitative level. After deriving a simple formula linking growth rate, carbon intake, and biosynthetic costs, we show that optimal growth results from the tradeoff between yield maximization and protein burden minimization. Empirical data confirm that E. coli growth is indeed close to Pareto-optimal over a broad range of growth rates. Moreover, we establish that, while most of the intaken carbon is diverted into biomass precursors, the efficiency of ATP synthesis is the key driver of the yield-cost tradeoff. These findings provide a quantitative perspective on carbon overflow, the origin of growth laws and the multidimensional optimality of E. coli metabolism.
The influence of spatial and temporal resolutions on the analysis of cell-cell interaction: a systematic study for time-lapse microscopy applications
Authors: Comes M. C. , Casti P. , Mencattini A. , Di Giuseppe D. , Mermet-Meillon F. , De Ninno A. , Parrini M. C. , Businaro L. , Di Natale C. , Martinelli E.
Published: May 2019

Cell-cell interactions are an observable manifestation of underlying complex biological processes occurring in response to diversified biochemical stimuli. Recent experiments with microfluidic devices and live cell imaging show that it is possible to characterize cell kinematics via computerized algorithms and unravel the effects of targeted therapies. We study the influence of spatial and temporal resolutions of time-lapse videos on motility and interaction descriptors with computational models that mimic the interaction dynamics among cells. We show that the experimental set-up of time-lapse microscopy has a direct impact on the cell tracking algorithm and on the derived numerical descriptors. We also show that, when comparing kinematic descriptors in two diverse experimental conditions, too low resolutions may alter the descriptors’ discriminative power, and so the statistical significance of the difference between the two compared distributions. The conclusions derived from the computational models were experimentally confirmed by a series of video-microscopy acquisitions of co-cultures of unlabelled human cancer and immune cells embedded in 3D collagen gels within microfluidic devices. We argue that the experimental protocol of acquisition should be adapted to the specific kind of analysis involved and to the chosen descriptors in order to derive reliable conclusions and avoid biasing the interpretation of results.
Author Correction: Magnesium intake and mortality due to liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort
Authors: Wu Lijun , Zhu Xiangzhu , Fan Lei , Kabagambe Edmond K. , Song Yiqing , Tao Menghua , Zhong Xiaosong , Hou Lifang , Shrubsole Martha J. , Liu Jie , Dai Qi
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure
Authors: Lawless Michael , Caldwell Jessica L. , Radcliffe Emma J. , Smith Charlotte E. R. , Madders George W. P. , Hutchings David C. , Woods Lori S. , Church Stephanie J. , Unwin Richard D. , Kirkwood Graeme J. , Becker Lorenz K. , Pearman Charles M. , Taylor Rebecca F. , Eisner David A. , Dibb Katharine M. , Trafford Andrew. W.
Published: May 2019

Heart failure (HF) is characterized by poor survival, a loss of catecholamine reserve and cellular structural remodeling in the form of disorganization and loss of the transverse tubule network. Indeed, survival rates for HF are worse than many common cancers and have not improved over time. Tadalafil is a clinically relevant drug that blocks phosphodiesterase 5 with high specificity and is used to treat erectile dysfunction. Using a sheep model of advanced HF, we show that tadalafil treatment improves contractile function, reverses transverse tubule loss, restores calcium transient amplitude and the heart’s response to catecholamines. Accompanying these effects, tadalafil treatment normalized BNP mRNA and prevented development of subjective signs of HF. These effects were independent of changes in myocardial cGMP content and were associated with upregulation of both monomeric and dimerized forms of protein kinase G and of the cGMP hydrolyzing phosphodiesterases 2 and 3. We propose that the molecular switch for the loss of transverse tubules in HF and their restoration following tadalafil treatment involves the BAR domain protein Amphiphysin II (BIN1) and the restoration of catecholamine sensitivity is through reductions in G-protein receptor kinase 2, protein phosphatase 1 and protein phosphatase 2 A abundance following phosphodiesterase 5 inhibition.
Honey bees increase their foraging performance and frequency of pollen trips through experience
Authors: Klein Simon , Pasquaretta Cristian , He Xu Jiang , Perry Clint , Søvik Eirik , Devaud Jean-Marc , Barron Andrew B. , Lihoreau Mathieu
Published: May 2019

Honey bee foragers must supply their colony with a balance of pollen and nectar to sustain optimal colony development. Inter-individual behavioural variability among foragers is observed in terms of activity levels and nectar vs. pollen collection, however the causes of such variation are still open questions. Here we explored the relationship between foraging activity and foraging performance in honey bees (Apis mellifera) by using an automated behaviour monitoring system to record mass on departing the hive, trip duration, presence of pollen on the hind legs and mass upon return to the hive, during the lifelong foraging career of individual bees. In our colonies, only a subset of foragers collected pollen, and no bee exclusively foraged for pollen. A minority of very active bees (19% of the foragers) performed 50% of the colony’s total foraging trips, contributing to both pollen and nectar collection. Foraging performance (amount and rate of food collection) depended on bees’ individual experience (amount of foraging trips completed). We argue that this reveals an important vulnerability for these social bees since environmental stressors that alter the activity and reduce the lifespan of foragers may prevent bees ever achieving maximal performance, thereby seriously compromising the effectiveness of the colony foraging force.
Environmental distribution of certain modified live-virus vaccines with a high safety profile presents a low-risk, high-reward to control zoonotic diseases
Authors: Head Jennifer R. , Vos Ad , Blanton Jesse , Müller Thomas , Chipman Richard , Pieracci Emily G. , Cleaton Julie , Wallace Ryan
Published: May 2019

Oral vaccines aid immunization of hard to reach animal populations but often contain live-attenuated viruses that pose risks of reversion to virulence or residual pathogenicity. Human risk assessment is crucial prior to vaccine field distribution but there is currently no standardized approach. We mapped exposure pathways by which distribution of oral vaccines may result in inoculation into people and applied a Markov chain to estimate the number of severe adverse events. We simulated three oral rabies vaccination (ORV) campaigns: (1) first generation ORV (SAD-B19) in foxes, (2) SAD-B19 in dogs, and (3) third generation ORV (SPBN GASGAS) in dogs. The risk of SAD-B19-associated human deaths was predicted to be low (0.18 per 10 million baits, 95% CI: 0.08, 0.36) when distributed to foxes, but, consistent with international concern, 19 times greater (3.35 per 10 million baits, 95% CI: 2.83, 3.98) when distributed to dogs. We simulated no deaths from SPBN GAS-GAS. Human deaths during dog campaigns were particularly sensitive to dog bite rate, and during wildlife campaigns to animal consumption rate and human contact rate with unconsumed baits. This model highlights the safety of third generation rabies vaccines and serves as a platform for standardized approaches to inform risk assessments.
Author Correction: Cream Cheese-Derived Lactococcus chungangensis CAU 28 Modulates the Gut Microbiota and Alleviates Atopic Dermatitis in BALB/c Mice
Authors: Kim Jong-Hwa , Kim Kiyoung , Kim Wonyong
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Agricultural and Physiological Responses of Tomato Plants Grown in Different Soilless Culture Systems with Saline Water under Greenhouse Conditions
Authors: Rodríguez-Ortega Wilbert M. , Martínez Vicente , Nieves Manuel , Simón I. , Lidón V. , Fernandez-Zapata J. C. , Martinez-Nicolas J. J. , Cámara-Zapata José M. , García-Sánchez Francisco
Published: May 2019

Tomato is the most important horticultural crop in the world. The yields for this crop are highest in Southeastern Spain. In this work we studied a commercial variety of tomato, with different soilless culture systems (deep flow technique, nutrient film technique, and the perlite substrate) and three levels of salinity (2.2, 6.3, and 10.2 dS·m−1) typical of Southeastern Spain. The irrigation management was carried out for optimizing the water use efficiency. Alterations in the water status of the plants, Cl− and Na+ toxicity, and nutritional imbalances altered the vegetative growth and physiology of the plants. The marketable yield was affected by both soilless culture system and salinity. Regarding the soilles culture system, yield decreased in the order: deep flow technique > perlite > nutrient film technique. The salinity treatments improved the fruits quality by increasing the total soluble solids and titratable acidity. Plants cultivated with the nutrient film technique had the highest concentrations of Cl− and Na+ and the highest Na+/K+ ratio. The concentrations of Cl− and Na+ in the plants were not related directly to the yield loss. Therefore, the influence of the toxicity, osmotic effect, and nutritional imbalance seems to have been responsible for the yield loss.
Author Correction: Sahel rainfall strength and onset improvements due to more realistic Atlantic cold tongue development in a climate model
Authors: Steinig S. , Harlaß J. , Park W. , Latif M.
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
A compact acoustic spanner to rotate macroscopic objects
Authors: Toninelli Ermes , Cox Mitchell A. , Gibson Graham M. , Brown Stuart D. , Edgar Matthew P. , Forbes Andrew , Padgett Miles J.
Published: May 2019

Waves can carry both linear and angular momentum. When the wave is transverse (e.g. light), the angular momentum can be characterised by the “spin” angular momentum associated with circular polarisation, and the “orbital” angular momentum (OAM) arising from the phase cross-section of the beam. When the wave is longitudinal (e.g. sound) there is no polarization and hence no spin angular momentum. However, a suitably phase-structured sound beam can still carry OAM. Observing the transfer of OAM from sound to a macroscopic object provides an excellent opportunity to study the exchange of energy between waves and matter. In this paper we show how to build a compact free-space acoustic spanner based on a 3D-printed sound-guiding structure and common electronic components. We first characterise the sound fields by measuring both phase and amplitude maps, and then show a video of our free-space acoustic spanner in action, in which macroscopic objects spin in a circular motion and change direction of rotation according to the handedness of the OAM acoustic field.
Association of Anticholinergic Use with Incidence of Alzheimer’s Disease: Population-based Cohort Study
Authors: Joung Kyung-in , Kim Sukil , Cho Yoon Hee , Cho Sung-il
Published: May 2019

Drugs with strong anticholinergic properties are used under a variety of conditions; however, they can cause various adverse effects including a negative impact on cognitive functions, with older adults being more susceptible to these effects. We explored whether the use of anticholinergic agents (ACs) affects the risk of Alzheimer’s disease (AD) in terms of incidence by using National Health Insurance Service elderly cohort database (2002–2013). As a result, AD risk was higher in subjects with an increased amount of prescriptions for strong ACs over a long period of time (9–12 years) than that in the least-exposed reference group (0–9 dose/year) [hazard ratio (HR) (95% confidence interval (95% CI)) 0.99 (0.95–1.03), 1.19 (1.12–1.26), 1.39 (1.30–1.50); in the 10–49 doses/year, 50–119 doses/year, and ≥120 doses/year groups]. Hazard ratios were particularly high in the young-old subgroup (60–64 years old in 2002) [HR (95% CI) 1.11 (1.04–1.22), 1.43 (1.25–1.65), 1.83 (1.56–2.14); in the 10–49 doses/year, 50–119 doses/year, and ≥120 doses/year groups]. Use of strong ACs dose-dependently increased the risk of AD in terms of incidence when exposure was followed up for 9 years or more, and the association was greater in the young-old subgroup.
The cell adhesion protein CAR is a negative regulator of synaptic transmission
Authors: Wrackmeyer Uta , Kaldrack Joanna , Jüttner René , Pannasch Ulrike , Gimber Niclas , Freiberg Fabian , Purfürst Bettina , Kainmueller Dagmar , Schmitz Dietmar , Haucke Volker , Rathjen Fritz G. , Gotthardt Michael
Published: May 2019

The Coxsackievirus and adenovirus receptor (CAR) is essential for normal electrical conductance in the heart, but its role in the postnatal brain is largely unknown. Using brain specific CAR knockout mice (KO), we discovered an unexpected role of CAR in neuronal communication. This includes increased basic synaptic transmission at hippocampal Schaffer collaterals, resistance to fatigue, and enhanced long-term potentiation. Spontaneous neurotransmitter release and speed of endocytosis are increased in KOs, accompanied by increased expression of the exocytosis associated calcium sensor synaptotagmin 2. Using proximity proteomics and binding studies, we link CAR to the exocytosis machinery as it associates with syntenin and synaptobrevin/VAMP2 at the synapse. Increased synaptic function does not cause adverse effects in KO mice, as behavior and learning are unaffected. Thus, unlike the connexin-dependent suppression of atrioventricular conduction in the cardiac knockout, communication in the CAR deficient brain is improved, suggesting a role for CAR in presynaptic processes.
Impact of ankylosing spondylitis on depression: a nationwide cohort study
Authors: Park Jin-Sung , Jang Hae-Dong , Hong Jae-Young , Park Ye-Soo , Han Kyungdo , Suh Seung-Woo , Park Si-Yong , Kim Bo-Taek
Published: May 2019

The aim of this study is to determine the relationship between AS and subsequent depression. This study was conducted using a nationwide dataset available in Korean National Health Insurance System (KNHIS). We identified 11,465 newly diagnosed AS patients and 57,325 patients without AS in the ratio of 1:5 matched by sex, age, and index date, between 2010 and 2014. We investigated any latent characteristics in the patients’ demographic information and chronic comorbidities that could trigger a depression when diagnosed with AS. By comparing the cohort data, the hazard ratio of developing subsequent depression in AS patients was calculated and adjusted based on several risk factors. Despite the adjustment of demographic variables and chronic comorbidities, the risk of depression was 2.21 times higher in the AS cohort than in the control group. Multivariate analysis showed that AS patients with female gender, old age and low-income status showed higher risks of developing depression. Additionally, the presence of chronic comorbidities including diabetes mellitus, hypertension, hyperlipidemia, cancer, stroke, and chronic kidney disease increased the patients’ risk of depression. The AS patients with stroke were reported to have the highest risk of depression. This population-based cohort study showed that AS significantly increased the subsequent risk of developing depression. Moreover, the development of a depression is influenced by certain demographic variables and different chronic comorbidities.
Mismatch between perceived family and individual chronotype and their association with sleep-wake patterns
Authors: Pereira-Morales Angela J. , Adan Ana , Casiraghi Leandro P. , Camargo Andrés
Published: May 2019

While social zeitgebers are known to shape diurnal preference, little research has been devoted to determining the contribution of the familiar group chronotype as social zeitgeber on individual circadian rhythms and sleep-wake patterns in adult subjects. The current study aimed to examine the matching between perceived family chronotype and individual chronotype and their relationship with sleep-wake patterns on weekdays and weekends, diurnal subjective somnolence, and substance consumption. Nine hundred and forty-two Colombian adults completed the Composite Scale of Morningness, the Epworth Sleepiness Scale, and responded to a questionnaire about circadian preferences of their family nucleus. We found evidence of a mismatch between perceived family and individual chronotype, mainly for morning-type individuals (Cohen’s Kappa = −0.231; p < 0.001). This mismatch was associated with diurnal subjective somnolence (β = 0.073; p < 0.001) and specific sleep-wake patterns (p < 0.01). In addition, subjects with evening-type families showed higher caffeine and alcohol consumption (p < 0.001). To our knowledge, this is the first study to assess and report the mismatching between perceived family and individual chronotypes, and it adds to the existing body of knowledge regarding the influence of social zeitgebers on circadian rhythms. This is particularly relevant since mismatching between circadian physiology and environmental cues have been shown to lead to diverse pathologies.
Goth migration induced changes in the matrilineal genetic structure of the central-east European population
Authors: Stolarek I. , Handschuh L. , Juras A. , Nowaczewska W. , Kóčka-Krenz H. , Michalowski A. , Piontek J. , Kozlowski P. , Figlerowicz M.
Published: May 2019

For years, the issues related to the origin of the Goths and their early migrations in the Iron Age have been a matter of hot debate among archaeologists. Unfortunately, the lack of new independent data has precluded the evaluation of the existing hypothesis. To overcome this problem, we initiated systematic studies of the populations inhabiting the contemporary territory of Poland during the Iron Age. Here, we present an analysis of mitochondrial DNA isolated from 27 individuals (collectively called the Mas-VBIA group) excavated from an Iron Age cemetery (dated to the 2nd-4th century A.D.) attributed to Goths and located near Masłomęcz, eastern Poland. We found that Mas-VBIA has similar genetic diversity to present-day Asian populations and higher diversity than that of contemporary Europeans. Our studies revealed close genetic links between the Mas-VBIA and two other Iron Age populations from the Jutland peninsula and from Kowalewko, located in western Poland. We disclosed the genetic connection between the Mas-VBIA and ancient Pontic-Caspian steppe groups. Similar connections were absent in the chronologically earlier Kowalewko and Jutland peninsula populations. The collected results seem to be consistent with the historical narrative that assumed that the Goths originated in southern Scandinavia; then, at least part of the Goth population moved south through the territory of contemporary Poland towards the Black Sea region, where they mixed with local populations and formed the Chernyakhov culture. Finally, a fraction of the Chernyakhov population returned to the southeast region of present-day Poland and established the archaeological formation called the “Masłomęcz group”.
Oxygen dissociation from ferrous oxygenated human hemoglobin:haptoglobin complexes confirms that in the R-state α and β chains are functionally heterogeneous
Authors: Ascenzi Paolo , Polticelli Fabio , Coletta Massimiliano
Published: May 2019

The adverse effects of extra-erythrocytic hemoglobin (Hb) are counterbalanced by several plasma proteins devoted to facilitate the clearance of free heme and Hb. In particular, haptoglobin (Hp) traps the αβ dimers of Hb, which are delivered to the reticulo-endothelial system by CD163 receptor-mediated endocytosis. Since Hp:Hb complexes show heme-based reactivity, kinetics of O2 dissociation from the ferrous oxygenated human Hp1-1:Hb and Hp2-2:Hb complexes (Hp1-1:Hb(II)-O2 and Hp2-2:Hb(II)-O2, respectively) have been determined. O2 dissociation from Hp1-1:Hb(II)-O2 and Hp2-2:Hb(III)-O2 follows a biphasic process. The relative amplitude of the fast and slow phases ranges between 0.47 and 0.53 of the total amplitude, with values of koff1 (ranging between 25.6 ± 1.4 s−1 and 29.1 ± 1.3 s−1) being about twice faster than those of koff2 (ranging between 13.8 ± 1.6 s−1 and 16.1 ± 1.2 s−1). Values of koff1 and koff2 are essentially the same independently on whether O2 dissociation has been followed after addition of a dithionite solution or after O2 displacement by a CO solution in the presence of dithionite. They correspond to those reported for the dissociation of the first O2 molecule from tetrameric Hb(II)-O2, indicating that in the R-state α and β chains are functionally heterogeneous and the tetramer and the dimer behave identically. Accordingly, the structural conformation of the α and β chains of the Hb dimer bound to Hp corresponds to that of the subunits of the Hb tetramer in the R-state.
Vision-related quality of life and symptom perception change over time in newly-diagnosed primary open angle glaucoma patients
Authors: Riva Ivano , Legramandi Lorenzo , Rulli Eliana , Konstas Anastasios G. , Katsanos Andreas , Oddone Francesco , Weinreb Robert N. , Quaranta Luciano ,   The Italian Study Group on QoL in Glaucoma, Varano L. , Carchedi T. , Talarico S. , Frezzotti P. , Parravano F. , Motolese I. , Bagaglia S. A. , Rossi G. C. M. , Lateri S. , Bossolesi L. , Carmassi L. , Rolle T. , Piccini R. , Ratiglia R. , Rossi A. , Gandolfi S. , Tagliavini V. , Ungaro N. , Fossarello M. , Cuccu A. , Zucca I. , Uva M. , Bonacci E. , Cardarella G. , Tognetto D. , Vattovani O. , Vallon P. , Iannacone F. , Fontana L. , Marchi S. , Manni G. L. , Jannetta D. , Roberti G. , Rossetti L. , Maggiolo E. , Oneta O. , Sborgia C. , Cantatore F. , Mastropasqua L. , Agnifili L. , Campos E. , Gizzi C. , Giannaccare G. , Pucci V. , Cassamali M. , Costagliola C. , Traverso C. , Scotto R. , Musolino M. , Landi L. , Bagnis A.
Published: May 2019

To evaluate the change over time of vision-related quality of life (QoL) and glaucoma symptoms in a population of newly-diagnosed primary open angle glaucoma (POAG) patients. Multicenter, prospective study. Consecutive newly-diagnosed POAG patients were enrolled and followed-up for one year. Follow-up visits were scheduled at 6 and 12 months from baseline. At each visit, vision-related QoL and glaucoma-related symptoms were assessed by the means of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the Glaucoma Symptom Scale (GSS), respectively. Trends over time for NEI-VFQ-25 and GSS scores were evaluated with longitudinal linear mixed models. One-hundred seventy-eight patients were included in the analysis. At baseline, early to moderate glaucoma stages were associated with higher scores for most GSS and NEI-VFQ-25 items, while lower best-corrected visual acuity was associated with lower scores for 4 of the 12 NEI-VFQ-25 items. During the follow-up, all the GSS scores, the NEI-VFQ-25 total score, and 7 of the 12 NEI-VFQ-25 scores significantly improved (p < 0.05). In multivariate model, higher increases of most GSS and NEI-VFQ-25 scores were modeled in patients with low scores at baseline. Vision-related QoL and glaucoma-related symptom perception significantly improved during the one-year follow-up in this population of newly diagnosed POAG patients.
Quadrature Frequency-Group Radar and its center estimation algorithms for small Vibrational Displacement
Authors: Kim Dong Kyoo , Kim Youjin
Published: May 2019

The quadrature continuous-wave (QCW) radar has been extensively studied for small vibrational displacement detection such as non-contact sensing of human vital signals. One of the challenges of the QCW radar is the IQ-imbalance and DC-offset estimation by using curve fitting algorithms. Many algorithms have been proposed and have shown that the fitting error increases when the displacement length is small, in which case sufficient data is not provided to the algorithms. This paper presents a quadrature frequency-group (QFG) radar which utilizes a group of frequencies to enhance the fitting performance even with the small displacement. The grouped-frequencies in the QFG radar gives more data than the single-tone of the QCW radar under the same displacement condition. This paper presents the framework and properties of the QFG radar. Some fitting algorithms for the QFG radar are presented and the most adequate algorithm is suggested by simulation and experiments. Simulation and experimental results shows that the QFG radar outperforms the QCW radar. Specifically, it is shown that the fitting accuracy of the QFG radar is up to 100 times better than the QCW radar in the experiment.
Transcription Factor HOXA9 is Linked to the Calcification and Invasion of Papillary Thyroid Carcinoma
Authors: Jin Yilan , Kim Hyeung Kyoo , Lee Jeonghun , Soh Euy Young , Kim Jang-Hee , Song Insun , Chung Yoon-Sok , Choi Yong Jun
Published: May 2019

Calcification is important for the diagnosis of papillary thyroid carcinoma (PTC). Runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteogenic differentiation, is reportedly related to PTC calcification and invasiveness. However, its regulatory role in this process is somewhat uncharacterized. Here, we attempted to identify genes that regulate RUNX2 and clarify its function in PTC carcinogenesis and calcification. The expression of RUNX2-upstream genes was evaluated by real-time PCR in Nthy-Ori 3-1 normal thyroid cells and TPC1 and BHP10-3 PTC cell lines. Luciferase and chromatin immunoprecipitation assays were performed with candidate genes after cloning the RUNX2 promoter. We found that RUNX2 promoter activity was enhanced by homeobox family A9 (HOXA9). Over-expression of HOXA9 was found to enhance alkaline phosphatase activity, mineralization, and in vitro tumour cell migration and invasion, whereas downregulation had the opposite effects. These results indicate that HOXA9, a positive regulator of RUNX2, can enhance calcification, migration, and invasion in PTC. Our data improve the understanding of the molecular mechanisms of microcalcification in PTC as well as tumorigenesis.
Virally-vectored vaccine candidates against white-nose syndrome induce anti-fungal immune response in little brown bats (Myotis lucifugus)
Authors: Rocke Tonie E. , Kingstad-Bakke Brock , Wüthrich Marcel , Stading Ben , Abbott Rachel C. , Isidoro-Ayza Marcos , Dobson Hannah E. , dos Santos Dias Lucas , Galles Kevin , Lankton Julia S. , Falendysz Elizabeth A. , Lorch Jeffrey M. , Fites J. Scott , Lopera-Madrid Jaime , White J. Paul , Klein Bruce , Osorio Jorge E.
Published: May 2019

White-nose syndrome (WNS) caused by the fungus, Pseudogymnoascus destructans (Pd) has killed millions of North American hibernating bats. Currently, methods to prevent the disease are limited. We conducted two trials to assess potential WNS vaccine candidates in wild-caught Myotis lucifugus. In a pilot study, we immunized bats with one of four vaccine treatments or phosphate-buffered saline (PBS) as a control and challenged them with Pd upon transfer into hibernation chambers. Bats in one vaccine-treated group, that received raccoon poxviruses (RCN) expressing Pd calnexin (CAL) and serine protease (SP), developed WNS at a lower rate (1/10) than other treatments combined (14/23), although samples sizes were small. The results of a second similar trial provided additional support for this observation. Bats vaccinated orally or by injection with RCN-CAL and RCN-SP survived Pd challenge at a significantly higher rate (P = 0.01) than controls. Using RT-PCR and flow cytometry, combined with fluorescent in situ hybridization, we determined that expression of IFN-γ transcripts and the number of CD4 + T-helper cells transcribing this gene were elevated (P < 0.10) in stimulated lymphocytes from surviving vaccinees (n = 15) compared to controls (n = 3). We conclude that vaccination with virally-vectored Pd antigens induced antifungal immunity that could potentially protect bats against WNS.
8.2 ka event North Sea hydrography determined by bivalve shell stable isotope geochemistry
Authors: Estrella-Martínez Juan , Ascough Philippa L. , Schöne Bernd R. , Scourse James D. , Butler Paul G.
Published: May 2019

The abrupt 8.2 ka cold event has been widely described from Greenland and North Atlantic records. However, its expression in shelf seas is poorly documented, and the temporal resolution of most marine records is inadequate to precisely determine the chronology of major events. A robust hydrographical reconstruction can provide an insight on climatic reaction times to perturbations to the Atlantic Meridional Overturning Circulation. Here we present an annually-resolved temperature and water column stratification reconstruction based on stable isotope geochemistry of Arctica islandica shells from the Fladen Ground (northern North Sea) temporally coherent with Greenland ice core records. Our age model is based on a growth increment chronology obtained from four radiometrically-dated shells covering the 8290–8100 cal BP interval. Our results indicate that a sudden sea level rise (SSLR) event-driven column stratification occurred between ages 8320–8220 cal BP. Thirty years later, cold conditions inhibited water column stratification but an eventual incursion of sub-Arctic waters into the North Sea re-established density-driven stratification. The water temperatures reached their minimum of ~3.7 °C 55 years after the SSLR. Intermittently-mixed conditions were later established when the sub-Arctic waters receded.
HDAC Regulates Transcription at the Outset of Axolotl Tail Regeneration
Authors: Voss S. Randal , Ponomareva Larissa V. , Dwaraka Varun B. , Pardue Kaitlin E. , Baddar Nour W. Al Haj , Rodgers A. Katherine , Woodcock M. Ryan , Qiu Qingchao , Crowner Anne , Blichmann Dana , Khatri Shivam , Thorson Jon S.
Published: May 2019

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited regeneration through the first 7 days, however after this time, regeneration commenced with variable outgrowth of tailfin tissue and abnormal patterning. Microarray analysis showed that romidepsin altered early, transcriptional responses at 3 and 6-hour post-amputation, especially targeting genes that are implicated in tumor cell death, as well as genes that function in the regulation of transcription, cell differentiation, cell proliferation, pattern specification, and tissue morphogenesis. Our results show that HDAC activity is required at the time of tail amputation to regulate the initial transcriptional response to injury and regeneration.
Effects of Burdock tea on recurrence of colonic diverticulitis and diverticular bleeding: An open-labelled randomized clinical trial
Authors: Mizuki Akira , Tatemichi Masayuki , Nakazawa Atsushi , Tsukada Nobuhiro , Nagata Hiroshi , Kinoshita Yoshikazu
Published: May 2019

Colonic diverticular bleeding (CDB) and acute colonic diverticulitis (ACD) show high recurrence rates. The establishment of optimal strategies that prevent the recurrence of CDB and ACD is a major concern among gastroenterologists. This study aimed to assess the efficacy of burdock tea for preventing CDB and ACD recurrences. Newly diagnosed patients with CDB (n = 91) or ACD (n = 70) were randomly assigned into two groups. The experimental group received 1.5 g of burdock tea three times a day, whereas the control group did not receive any treatment. The median (interquartile range) of observation for recurrence of CDB or ACD was 22.0 (14.1) months and 30.3 (18.6), respectively. The burdock tea treatment showed significant preventive effects on recurrence of ACD. A lower ACD recurrence rate (5/47 [10.6%] vs. 14/44 [31.8%]) and longer recurrence-free duration was observed in the burdock tea group (59.3 months [95% CI: 54.0–64.7] vs. 45.1 months [95% CI: 37.1–53.0] by the Kaplan-Meier analysis; p = 0.012 by log rank test) than in the control group, although there was no significant preventive effects on the CDB recurrence. This randomized clinical trial demonstrated that daily intake of burdock tea could be an effective strategy for prevention of ACD recurrence, but not for CDB recurrence.
Dopamine blockade impairs the exploration-exploitation trade-off in rats
Authors: Cinotti François , Fresno Virginie , Aklil Nassim , Coutureau Etienne , Girard Benoît , Marchand Alain R. , Khamassi Mehdi
Published: May 2019

In a volatile environment where rewards are uncertain, successful performance requires a delicate balance between exploitation of the best option and exploration of alternative choices. It has theoretically been proposed that dopamine contributes to the control of this exploration-exploitation trade-off, specifically that the higher the level of tonic dopamine, the more exploitation is favored. We demonstrate here that there is a formal relationship between the rescaling of dopamine positive reward prediction errors and the exploration-exploitation trade-off in simple non-stationary multi-armed bandit tasks. We further show in rats performing such a task that systemically antagonizing dopamine receptors greatly increases the number of random choices without affecting learning capacities. Simulations and comparison of a set of different computational models (an extended Q-learning model, a directed exploration model, and a meta-learning model) fitted on each individual confirm that, independently of the model, decreasing dopaminergic activity does not affect learning rate but is equivalent to an increase in random exploration rate. This study shows that dopamine could adapt the exploration-exploitation trade-off in decision-making when facing changing environmental contingencies.
Structure and stability of the coral microbiome in space and time
Authors: Dunphy Courtney M. , Gouhier Tarik C. , Chu Nathaniel D. , Vollmer Steven V.
Published: May 2019

Although it is well established that the microbial communities inhabiting corals perform key functions that promote the health and persistence of their hosts, little is known about their spatial structure and temporal stability. We examined the natural variability of microbial communities associated with six Caribbean coral species from three genera at four reef sites over one year. We identified differences in microbial community composition between coral genera and species that persisted across space and time, suggesting that local host identity likely plays a dominant role in structuring the microbiome. However, we found that microbial community dissimilarity increased with geographical distance, which indicates that regional processes such as dispersal limitation and spatiotemporal environmental heterogeneity also influence microbial community composition. In addition, network analysis revealed that the strength of host identity varied across coral host genera, with species from the genus Acropora having the most influence over their microbial community. Overall, our results demonstrate that despite high levels of microbial diversity, coral species are characterized by signature microbiomes that are stable in both space and time.