bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitroscreening of temperate climate forages from a variety of woody plants for their potential to mitigate ruminal methane and ammonia formation
Authors: Terranova M. , Kreuzer M. , Braun U. , Schwarm A.
Published: November 2018

Feeding phenol-containing plants to ruminants has the potential to mitigate both methane and ammonia formation. In the present study, mostly woody plants, such as the leaves of trees and shrubs, were tested for their influence onin vitrofermentation. The plants selected grow naturally under temperate climatic conditions, are usually available in bulk and do not directly compete with human food production. The detailed screening included whole plants or parts of different plant species reporting their effects on methane and/or ammonia formation. The plant materials were added at 167 mg/g of total dry matter (DM) to a common total mixed ration and incubated for 24 h with the Hohenheim gas test method. The results fromin vitrofermentation were also used to determine the net energy of lactation and utilizable crude protein in the complete diets. Thirteen out of 18 test materials did not impair the organic matter (OM) digestibility of the diet. Ammonia concentrations decreased up to 35% when adding any of the test materials. Methane formation per unit of feed DM and per unit of digestible OM was lowered by 13 of the 18 test materials from 12 to 28% and 5 to 20%, respectively. In conclusion, a number of plant materials tested have the potential to mitigate ruminal ammonia and methane formation without adversely affecting digestibility. The leaves ofBetula pendula,Corylus avellana,Ribes nigrum,Vitis viniferaand the aerial part ofGeum urbanumwere particularly promising in this respect.
Top Management Human Capital, Inventor Mobility, and Corporate Innovation
Authors: Chemmanur Thomas J. , Kong Lei , Krishnan Karthik , Yu Qianqian
Published: November 2018

Using panel data on top management characteristics and a management quality factor constructed using common factor analysis on individual management quality measures, we analyze the relation between top firm management quality and corporate innovation input and output. We show that top management quality is an important determinant of corporate innovation, with individual aspects of management quality affecting innovation in younger and older firms differently. Further, firms with higher top management quality engage in more risky (“explorative”) innovation strategies. Finally, hiring more and higher-quality inventors is an important channel through which firms with higher management quality achieve greater innovation output.
Model systems for investigating disease processes in neurocysticercosis
Authors: de Lange Anja , Mahanty Siddhartha , Raimondo Joseph V.
Published: November 2018

Neurocysticercosis (NCC) occurs following brain infection by larvae of the cestodeTaenia solium. It is the leading cause of preventable epilepsy worldwide and therefore constitutes a critical health challenge with significant global relevance. Despite this, much is still unknown about many key pathogenic aspects of the disease, including how cerebral infection withT. soliumresults in the development of seizures. Over the past century, valuable mechanistic insights have been generated using both clinical studies and animal models. In this review, we critically assess model systems for investigating disease processes in NCC. We explore the respective strengths and weaknesses of each model and summarize how they have contributed to current knowledge of the disease. We call for the continued development of animal models of NCC, with a focus on novel strategies for understanding this debilitating but often neglected disorder.
Species and site contributions toβ-diversity in fleas parasitic on the Palearctic small mammals: ecology, geography and host species composition matter the most
Authors: Krasnov Boris R. , Shenbrot Georgy I. , Warburton Elizabeth M. , van der Mescht Luther , Surkova Elena N. , Medvedev Sergei G. , Pechnikova Nadezhda , Ermolova Natalia , Kotti Boris K. , Khokhlova Irina S.
Published: November 2018

Theβ-diversity of fleas parasitic on small mammals in 45 regions of the Palearctic was partitioned into species [species contributions toβ-diversity (SCBD)] and site ( = assemblage) contributions [local contributions toβ-diversity (LCBD)]. We asked what are the factors affecting SCBD and LCBD and tested whether (a) variation in ecological, morphological, life history and geographic traits of fleas can predict SCBD and (b) variation in flea and host community metrics, off-host environmental factors, host species composition of flea assemblages can predict LCBD. We used spatial variables to describe geographic distribution of flea assemblages with various LCBD values. SCBD significantly increased with an increase in abundance and a decrease in phylogenetic host specificity of a flea as well as with size and latitude of its geographic range, but was not associated with any morphological/life history trait. LCBD of flea assemblages did not depend on either flea or host species richness or environmental predictors, but was significantly affected by compositional uniqueness ( = LCBD) of regional host assemblages and variables describing their species composition. In addition, variation in LCBD was also explained by broad-to-moderate-scale spatial variables. We conclude that SCBD of fleas could be predictedviatheir ecological and geographic traits, whereas LCBD of their assemblages could be predictedviahost composition.
Relevance in Undergraduate Neurological Teaching
Authors: Murray T. J.
Published: November 2018

About 10% of patients consulting a family practitioner have neurological complaints, and about 2% ultimately receive a neurological diagnosis As it is not possible to train enough neurologists for these patients, graduating medical students must be competent and confident in assessing neurological problems, particularly those that are common, treatable or require emergency management.

An evaluation was made of the neurological problems commonly seen in family practice, the difficulties in managing neurological problems by the family practitioner and the criteria for referral to a neurologist. To evaluate the teaching of medical students and house staff, the types of problems seen in a teaching hospital neurology service were examined.

As a result of this study an approach to the training of physicians is outlined to assist them to handle confidently and competently the neurological problems they will see in daily practice.
Does early maternal responsiveness buffer prenatal tobacco exposure effects on young children's behavioral disinhibition?
Authors: Clark Caron A. C. , Massey Suena H. , Wiebe Sandra A. , Espy Kimberly Andrews , Wakschlag Lauren S.
Published: November 2018

Children with prenatal tobacco exposure (PTE) exhibit early self-regulatory impairments, reflecting a life-course persistent propensity toward behavioral disinhibition. Previously, we demonstrated the protective role of parental responsiveness for reducing the risk of exposure-related disruptive behavior in adolescence. Here, we expanded this line of inquiry, examining whether responsiveness moderates the relation of PTE to a broader set of behavioral disinhibition features in early childhood and testing alternative diathesis-stress versus differential susceptibility explanatory models. PTE was assessed prospectively using interviews and bioassays in the Midwestern Infant Development Study (MIDS). Mother-child dyads (N = 276) were re-assessed at approximately 5 years of age in a preschool follow-up. We quantified maternal responsiveness and child behavioral disinhibition using a combination of directly observed activities in the lab and developmentally sensitive questionnaires. Results supported a diathesis-stress pattern. Children with PTE and less responsive mothers showed increased disruptive behavior and lower effortful control compared with children without PTE. In contrast, exposed children with more responsive mothers had self-regulatory profiles similar to their non-exposed peers. We did not observe sex differences. Findings provide greater specification of the protective role of maternal responsiveness for self-regulation in children with PTE and help clarify mechanisms that may underscore trajectories of exposure-related behavioral disinhibition.
Evaluation of Health Care Services Provided in Political Public Meetings in Turkey: A Forgotten Detail in Politics
Authors: Ceyhan Mehmet Ali , Demir Gültekin Günhan , Güler Gamze Babur
Published: November 2018

Background

Political parties in Turkey execute political public meetings (PPMs) during their election campaign for members of the parliament (MoP). A great number of people attend these meetings. No guidelines exist regarding preparation and organization of health care services provided during these meetings. Furthermore, there is no study evaluating health care problems encountered in previous PPMs.

Objective

Political parties arranged PPMs in 2015 during the election campaign for general election of MoP. The present study aimed to investigate the context of health care services, the distribution of assigned health staff, as well as the number and the symptoms of patients admitted in health care tents in these PPMs.

Methods

Two general elections for MoP were done in Turkey on June 7, 2015 and November 1, 2015. Health care services were provided by the City Emergency Medical Services Department (CEMSD) in the cities. Demographic characteristics, symptoms, comorbid conditions, treatment, discharge, and hospital transfer of the patients were obtained from patient medical registration records. Information about the distribution and the number of the assigned staff was received from local CEMSDs. The impact of variables such as the number of attendees, heat index, humidity, and the day of the week on the number of patients and the patient presentation rate (PPR) were analyzed.

Results

A total of 97 PPMs were analyzed. The number of total attendees was 5,265,450 people. The number of patients seeking medical help was 1,991. The PPR was 0.5 (0.23-0.91) patients per 1,000 attendees. Mean age of the patients was 40 (SD=19) years old while 1,174 (58.9%) of the patients were female. A total of 1,579 patients were treated in the tents and returned to the PPM following treatment. Two-hundred and three patients were transferred to a hospital by ambulance. Transfer-to-hospital ratio (TTHR) was 0.05 (0.0-0.13) patients per 1,000 attendees. None of the patients suffered sudden cardiac death (SCD) or cardiac arrest. Medical conditions were the main cause for admission. The most common symptoms were dizziness, low blood pressure, fatigue, and hypertension, respectively. The most commonly used medical agents included pain killers and myorelaxants. The number of attendees, heat index, and weekend days were positively correlated with the number of the patients.

Conclusion

: The majority of medical conditions encountered in PPMs are easily treatable in health care tents settled in the meeting area. The number of attendees, heat index, and weekend days are factors associated with the number of patients.

CeyhanMA, DemirGG, GülerGB. Evaluation of health care services provided in political public meetings in Turkey: a forgotten detail in politics. Prehosp Disaster Med. 2018;33(6):607–613.
Neuroanatomical features and its usefulness in classification of patients with PANDAS
Authors: Cabrera Brenda , Romero-Rebollar César , Jiménez-Ángeles Luis , Genis-Mendoza Alma D. , Flores Julio , Lanzagorta Nuria , Arroyo María , de la Fuente-Sandoval Camilo , Santana Daniel , Medina-Bañuelos Verónica , Sacristán Emilio , Nicolini Humberto
Published: November 2018

Objective

An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype.

Methods

Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA.

Results

The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls.

Conclusion

The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.
Clinical experience using Delta 4 phantom for pretreatment patient-specific quality assurance in modern radiotherapy
Authors: Srivastava R. P. , De Wagter C.
Published: November 2018

Purpose

In advanced radiotherapy techniques such as intensity-modulated radiation therapy (IMRT), the quality assurance (QA) process is essential. The aim of the study was to assure the treatment planning dose delivered during delivery of complex treatment plans. The QA standard is to perform patient-specific comparisons between planned doses and doses measured in a phantom.

Materials and method

The Delta 4 phantom (Scandidos, Uppsala, Sweden) has been used in this study. This device consists of diode matrices in two orthogonal planes inserted in a cylindrical acrylic phantom. Each diode is sampled per beam pulse so that the dose distribution can be evaluated on segment-by-segment, beam-by-beam, or as a composite plan from a single set of measurements. Ninety-five simple and complex radiotherapy treatment plans for different pathologies, planned using a treatment planning system (TPS) were delivered to the QA device. The planned and measured dose distributions were then compared and analysed. The gamma index was determined for different pathologies.

Results

The evaluation was performed in terms of dose deviation, distance to agreement and gamma index passing rate. The measurements were in excellent agreement between with the calculated dose of the TPS and the QA device. Overall, good agreement was observed between measured and calculated doses in most cases with gamma values above 1 in >95% of measured points. Plan results for each test met the recommended dose goals.

Conclusion

The delivery of IMRT and volumetric-modulated arc therapy (VMAT) plans was verified to correspond well with calculated dose distributions for different pathologies. We found the Delta 4 device is accurate and reproducible. Although Delta4 appears to be a straightforward device for measuring dose and allows measure in real-time dosimetry QA, it is a complex device and careful quality control is required before its use.
Okay to Stay? A new plan to help people with long-term conditions remain in their own homes
Authors: Chapman Helen , Farndon Lisa , Matthews Rebekah , Stephenson John
Published: November 2018

Aims

To assess the ‘Okay to Stay’ plan to investigate if this reduces visits to emergency departments, unplanned admissions and elective admission to hospital in elderly patients with long-term health conditions.

Background

The incidence of long-term conditions is rising as the elderly population increases, resulting in more people from this group attending emergency departments and being admitted to hospital. Okay to Stay is a simple plan for people with long-term conditions to help them remain in their own home if they suffer an acute exacerbation in their health. It was co-designed with professional and patient representatives with the aim of empowering patients and their carers to more effectively manage their long-term conditions.

Methods

Data from 50 patients (20 males, 30 females, mean baseline age 77.5 years) were compared 12 months before implementation of the plan and in the subsequent 12 months, with the significance of effects assessed at the 5 per cent significance level using t-tests.

Findings

Visits to emergency departments were reduced by 1.86; unplanned emergency admissions were reduced by 1.28 and planned elective admissions were raised by 0.22 admissions per annum. The reduction in visits to the emergency department was significant (p = 0.009) and the reduction in emergency admissions was significant (p = 0.015). The change in elective admissions was not significant (p = 0.855). The Okay to Stay plan is effective in reducing visits to the emergency department and unplanned hospital admissions in people with long-term conditions. This is a positive step to supporting vulnerable and complex patients who are cared for at home, and facilitates the recognition by the individual of the possibility to stay at home with the support of health professionals. There are potential cost benefits to the investment of initiating an Okay to Stay plan through the avoidance of visits to the emergency department and non-elective admissions to hospital.
Combining formal and informal contract enforcement in a developed legal system: a latent class approach
Authors: Mike Károly , Kiss Gábor
Published: November 2018

How do firms combine a broad range of contract enforcement mechanisms into coherent governance structures? How often are distinct structures used in an economy? We develop a new empirical approach, based on latent class analysis, to answer these questions. Economy-level data from Hungary are used to derive a data-driven typology of contractual governance between firms. The joint use of law, morality, self-enforcing contracts, reputation and community norms is examined. They are shown to be combined into bilateral, third-party or comprehensive governance structures. The crucial governance choice is whether to move beyond bilateralism and, if yes, whether to use a mixture of (formal and informal) third-party mechanisms as a substitute or a complement. Complementarity is much more common. We find no instances of ‘impersonal exchange’; the law never stands alone. By implication, economic development may be best understood as a process from a narrower towards a broader set of enforcement mechanisms.
Improved Simulation of Frozen‐Thawing Process in Land Surface Model (CLM4.5)
Authors: Yang Kai , Wang Chenghai , Li Shiyue
Published: November 2018

Soil freezing‐thawing cycle is a hallmark feature of the land surface over cold regions. Variations in soil moisture and temperature during frozen‐thawing (FT) process are important for water and energy exchange between land and atmosphere. Results of regional simulations by Community Land Model version 4.5 (CLM4.5) over the Tibetan Plateau show that error of daily soil temperature is within 3 °C and error of daily soil moisture is with 0.10 mm3/mm3 in FT process, averaged at 10 sites of whole Tibetan Plateau. Single‐point simulations show that model biases partly attribute to uncertainties of initial condition and soil category data; excluding impacts of model setting, large biases of soil moisture still exist during soil thawing, and CLM4.5 fails to simulate the diurnal cycle of soil moisture in this period. Modifications of the FT parameterizations in CLM4.5 are proposed, which include (1) use of virtual temperature (Tv) instead of constant freezing point to determine occurring of phase change, (2) introduction of phase change efficiency (ε) to optimize variation rate of soil temperature and moisture in FT process, and (3) consideration of inferred impacts of phase change on soil heat conduction. Single‐point and global simulations show that compared to original parameterizations in CLM4.5, these modifications can reproduce the features of daily and diurnal variations in soil moisture and make simulation in FT process closer to the observations.
Neogene Modifications of Circulation in the Northeastern African‐Southern Ocean Gateway
Authors: Fischer Maximilian D. , Uenzelmann‐Neben Gabriele
Published: November 2018

In the African‐Southern Ocean gateway, several water masses originating in the Atlantic, Indian, and Southern oceans meet and mix. As a consequence, the gateway is crucial for the maintenance of the global thermohaline circulation. Newly acquired multichannel seismic reflection data collected across the southern Mozambique Ridge are used to reconstruct the impact of paleoceanographic modifications on the Neogene and Quaternary circulation in the northeastern African‐Southern Ocean gateway. The data show the occurrence of mid‐Miocene (~15 Ma) to early Pliocene (~5 Ma) contourite drifts and erosional features interpreted as evidence for the onset of current‐controlled sedimentation in the late Neogene resulting from mid‐Miocene cooling and closure of the Indonesian gateway. The Quaternary is characterized by a relocation of Antarctic Bottom Water inflow and the inception of two branches of the North Atlantic Deep Water circulation subsequent to the final closure of the Central American Seaway and the Northern Hemisphere Glaciation. Therefore, the two events triggered the onset of unhindered deep and bottom water circulation from the Atlantic into the Indian Ocean, whereas the Antarctic Intermediate Water circulation decreased due to the final closure of the Indonesian gateway. Our results show that tectonic and climatic events, which themselves may be linked, continuously modified the Cenozoic paleoceanic circulation in the African‐Southern Ocean gateway, and indicate that ocean gateways governing the global water mass exchange act as an excellent location to reconstruct such modifications based on the interpretation of contourite drifts and erosional features.
Crack Models of Repeating Earthquakes Predict Observed Moment‐Recurrence Scaling
Authors: Cattania C. , Segall P.
Published: November 2018

Small repeating earthquakes are thought to represent rupture of isolated asperities loaded by surrounding creep. The observed scaling between recurrence interval and seismic moment, Tr∼M1/6, contrasts with expectation assuming constant stress drop and no aseismic slip (Tr∼M1/3). Here we demonstrate that simple crack models of velocity‐weakening asperities in a velocity‐strengthening fault predict the M1/6 scaling; however, the mechanism depends on asperity radius, R. For small asperities (
, where
is the nucleation radius) numerical simulations with rate‐state friction show interseismic creep penetrating inward from the edge, and earthquakes nucleate in the center and rupture the entire asperity. Creep penetration accounts for ∼25% of the slip budget, the nucleation phase takes up a larger fraction of slip. Stress drop increases with increasing R; the lack of self‐similarity being due to the finite nucleation dimension. For
simulations exhibit simple cycles with ruptures nucleating from the edge. Asperities with
exhibit complex cycles of partial and full ruptures. Here Tr is explained by an energy criterion: full rupture requires that the energy release rate everywhere on the asperity at least equals the fracture energy, leading to the scaling Tr∼M1/6. Remarkably, in spite of the variability in behavior with source dimension, the scaling of Tr with stress drop Δτ, nucleation length and creep rate vpl is the same across all regimes:
. This supports the use of repeating earthquakes as creepmeters and provides a physical interpretation for the scaling observed in nature.
Modeling High Stress Drops, Scaling, Interaction, and Irregularity of Repeating Earthquake Sequences Near Parkfield
Authors: Lui Semechah K. Y. , Lapusta Nadia
Published: November 2018

Repeating earthquake sequences have been actively investigated to clarify many aspects of earthquake physics. The two particularly well‐studied sequences, known as the Los Angeles and San Francisco repeaters, have several intriguing observations, including their long (for the seismic moment) recurrence times that would suggest stress drops of 300 MPa based on typical assumptions, near‐syncronized timing prior to 2004, and higher than typical inferred stress drops (of 25 to 65 MPa, up to 90 MPa locally), but not as high as the recurrence times suggest. Here we show that all these observations are self‐consistent, in the sense that they can be reproduced in a single fault model. The suitable models build on the standard rate‐and‐state fault models, with velocity‐weakening patches imbedded into a velocity‐strengthening region, by adding either enhanced dynamic weakening during seismic slip or elevated normal stress on the patches, or both, to allow for the higher stress drops. Such models are able to match the observed average properties of the San Francisco and Los Angeles repeaters, as well as the overall nontrivial scaling between the recurrence time and seismic moment exhibited by many repeating sequences as a whole, for reasonable parameter choices based on experiments and theoretical studies. These models are characterized by the occurrence of substantial and variable aseismic slip at the locations of the repeating sources, which explains their atypical relation between recurrence interval and seismic moment, induces variability in the repeating source properties as observed, and results in their neither slip‐ nor time‐predictable behavior.
On the Formation Mechanism for Wintertime Extreme Precipitation Events Over the Southeastern Tibetan Plateau
Authors: Huang Wenyu , Qiu Tianpei , Yang Zifan , Lin Daiyu , Wright Jonathon S. , Wang Bin , He Xinsheng
Published: November 2018

The formation mechanism for wintertime extreme precipitation events over the southeastern Tibetan Plateau (SETP) is explored. The crucial step in the development of these events was the emergence of a cyclonic anomaly above the Tibetan Plateau. Wave activity fluxes along a Rossby wave train embedded in the subtropical jet stream (i.e., the circumglobal teleconnection) played the dominant role in producing this cyclonic anomaly, supported by weaker wave activity fluxes along a second Rossby wave train originating over Scandinavia. The cyclonic anomaly then moved over the SETP, favored strong updrafts, large‐scale moisture convergence, and intense precipitation. Extreme precipitation was more likely to ensue when the arrival of the cyclonic anomaly was preceded by persistent warm anomalies over the SETP, which favored moisture accumulation there. Temperatures above the SETP dropped sharply around the onset of the extreme precipitation. A heat budget analysis indicates that adiabatic cooling associated with convective ascent along the downstream edge of the cyclone played a leading role in this temperature drop, while a cold air intrusion associated with an anticyclonic anomaly over western Siberia (one center of action along the second wave train) played a complementary role. An Eulerian moisture budget analysis shows that variations in precipitable water delayed the onset and enhanced the intensity of these events, with moisture for precipitation delivered to the SETP mainly through the western and southern boundaries. A companion Lagrangian moisture source analysis reveals that the land areas south of the Tibetan Plateau typically contributed 78.7% of the moisture supply for these events.
Assessment of the Radiation Environment at Commercial Jet‐Flight Altitudes During GLE 72 on 10 September 2017 Using Neutron Monitor Data
Authors: Mishev A. L. , Usoskin I. G.
Published: November 2018

As a result of intense solar activity during the first 10 days of September, a ground level enhancement occurred on 10 September 2017. Here we computed the effective dose rates in the polar region at several altitudes during the event using the derived rigidity spectra of the energetic solar protons. The contribution of different populations of energetic particles, namely, galactic cosmic rays and solar protons, to the exposure is explicitly considered and compared. We also assessed the exposure of a crew members/passengers to radiation at different locations and at several cruise flight altitudes and calculated the received doses for two typical intercontinental flights. The estimated received dose during a high latitude, 40 kft, ∼10‐hr flight is ∼100 μSv.
Selective colonization ability of human fecal microbes in different mouse gut environments
Authors: Zhou Wei , Chow Kin-hoe , Fleming Elizabeth , Oh Julia
Published: November 2018

Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.
Prevention of radiation-induced bystander effects by agents that inactivate cell-free chromatin released from irradiated dying cells
Authors: Kirolikar Saurabh , Prasannan Preeti , Raghuram Gorantla V. , Pancholi Namrata , Saha Tannishtha , Tidke Pritishkumar , Chaudhari Pradip , Shaikh Alfina , Rane Bhagyeshri , Pandey Richa , Wani Harshada , Khare Naveen K. , Siddiqui Sophiya , D’souza Jenevieve , Prasad Ratnam , Shinde Sushma , Parab Sailee , Nair Naveen K. , Pal Kavita , Mittra Indraneel
Published: November 2018

Radiation-induced bystander effect (RIBE) is a poorly understood phenomenon wherein non-targeted cells exhibit effects of radiation. We have reported that cell-free chromatin (cfCh) particles that are released from dying cells can integrate into genomes of surrounding healthy cells to induce DNA damage and inflammation. This raised the possibility that RIBE might be induced by cfCh released from irradiated dying cells. When conditioned media from BrdU-labeled irradiated cells were passed through filters of pore size 0.22 µm and incubated with unexposed cells, BrdU-labeled cfCh particles could be seen to readily enter their nuclei to activate H2AX, active Caspase-3, NFκB, and IL-6. A direct relationship was observed with respect to activation of RIBE biomarkers and radiation dose in the range of 0.1–50 Gy. We confirmed by FISH and cytogenetic analysis that cfCh had stably integrated into chromosomes of bystander cells and had led to extensive chromosomal instability. The above RIBE effects could be abrogated when conditioned media were pre-treated with agents that inactivate cfCh, namely, anti-histone antibody complexed nanoparticles (CNPs), DNase I and a novel DNA degrading agent Resveratrol-copper (R-Cu). Lower hemi-body irradiation with γ-rays (0.1–50 Gy) led to activation of H2AX, active Caspase-3, NFκB, and IL-6 in brain cells in a dose-dependent manner. Activation of these RIBE biomarkers could be abrogated by concurrent treatment with CNPs, DNase I and R-Cu indicating that activation of RIBE was not due to radiation scatter to the brain. RIBE activation was seen even when mini-beam radiation was delivered to the umbilical region of mice wherein radiation scatter to brain was negligible and could be abrogated by cfCh inactivating agents. These results indicate that cfCh released from radiation-induced dying cells are activators of RIBE and that it can be prevented by treatment with appropriate cfCh inactivating agents.
PLOD3 promotes lung metastasis via regulation of STAT3
Authors: Baek Jeong-Hwa , Yun Hong Shik , Kwon Gyoo Taik , Kim Ju-Young , Lee Chang-Woo , Song Jie-Young , Um Hong-Duck , Kang Chang-Mo , Park Jong Kuk , Kim Jae-Sung , Kim Eun Ho , Hwang Sang-Gu
Published: November 2018

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3), a membrane-bound homodimeric enzyme, hydroxylates lysyl residues in collagen-like peptides; however, its role in lung cancer is unknown. This study aimed to investigate the role of PLOD3 as a pro-metastatic factor and to elucidate the underlying mechanism. First, we experimentally confirmed the release of PLOD3 in circulation in animal models, rendering it a potential serum biomarker for lung cancer in humans. Thereafter, we investigated the effects of PLOD3 overexpression and downregulation on cancer cell invasion and migration in vitro and in vivo, using human lung cancer cell lines and a mouse tumor xenograft model, respectively. Further, PLOD3 levels were determined in lung tissue samples from lung cancer patients. Functional analyses revealed that PLOD3 interacts with STAT3, thereby expressing matrix metalloproteinases (MMP-2 and MMP-9) and with urokinase plasminogen activator (uPA) to enhance tumor metastasis. PLOD3 and the STAT3 pathway were significantly correlated in the metastatic foci of lung cancer patients; PLOD3–STAT3 levels were highly correlated with a poor prognosis. These results indicate that PLOD3 promotes lung cancer metastasis in a RAS-MAP kinase pathway-independent manner. Therefore, secreted PLOD3 serves as a potent inducer of lung cancer metastasis and a potential therapeutic target to enhance survival in lung cancer.
Detecting heritable phenotypes without a model using fast permutation testing for heritability and set-tests
Authors: Schweiger Regev , Fisher Eyal , Weissbrod Omer , Rahmani Elior , Müller-Nurasyid Martina , Kunze Sonja , Gieger Christian , Waldenberger Melanie , Rosset Saharon , Halperin Eran
Published: November 2018

Testing for association between a set of genetic markers and a phenotype is a fundamental task in genetic studies. Standard approaches for heritability and set testing strongly rely on parametric models that make specific assumptions regarding phenotypic variability. Here, we show that resulting p-values may be inflated by up to 15 orders of magnitude, in a heritability study of methylation measurements, and in a heritability and expression quantitative trait loci analysis of gene expression profiles. We propose FEATHER, a method for fast permutation-based testing of marker sets and of heritability, which properly controls for false-positive results. FEATHER eliminated 47% of methylation sites found to be heritable by the parametric test, suggesting a substantial inflation of false-positive findings by alternative methods. Our approach can rapidly identify heritable phenotypes out of millions of phenotypes acquired via high-throughput technologies, does not suffer from model misspecification and is highly efficient.
Tuning the balance between dispersion and entropy to design temperature-responsive flexible metal-organic frameworks
Authors: Wieme J. , Lejaeghere K. , Kresse G. , Van Speybroeck V.
Published: November 2018

Temperature-responsive flexibility in metal-organic frameworks (MOFs) appeals to the imagination. The ability to transform upon thermal stimuli while retaining a given crystalline topology is desired for specialized sensors and actuators. However, rational design of such shape-memory nanopores is hampered by a lack of knowledge on the nanoscopic interactions governing the observed behavior. Using the prototypical MIL-53(Al) as a starting point, we show that the phase transformation between a narrow-pore and large-pore phase is determined by a delicate balance between dispersion stabilization at low temperatures and entropic effects at higher ones. We present an accurate theoretical framework that allows designing breathing thermo-responsive MOFs, based on many-electron data for the dispersion interactions and density-functional theory entropy contributions. Within an isoreticular series of materials, MIL-53(Al), MIL-53(Al)-FA, DUT-4, DUT-5 and MIL-53(Ga), only MIL-53(Al) and MIL-53(Ga) are proven to switch phases within a realistic temperature range.
Determination of the two-dimensional distributions of gold nanorods by multiwavelength analytical ultracentrifugation
Authors: Wawra Simon E. , Pflug Lukas , Thajudeen Thaseem , Kryschi Carola , Stingl Michael , Peukert Wolfgang
Published: November 2018

Properties of nanoparticles are influenced by various parameters like size, shape or composition. Comprehensive high throughput characterization techniques are urgently needed to improve synthesis, scale up to production and make way for new applications of multidimensional particulate systems. In this study, we present a method for measuring two-dimensional size distributions of plasmonic nanorods in a single experiment. Analytical ultracentrifuge equipped with a multiwavelength extinction detector is used to record the optical and sedimentation properties of gold nanorods simultaneously. A combination of sedimentation and extinction properties, both depending on diameter and length of the dispersed nanorods, is used to measure two-dimensional distributions of gold nanorod samples. The length, diameter, aspect ratio, volume, surface and cross-sectional distributions can be readily obtained from these results. As the technique can be extended to other non-spherical plasmonic particles and can be used for determining relative amounts of particles of different shapes it provides complete and quantitative insights into particulate systems.
Graphene controlled Brewster angle device for ultra broadband terahertz modulation
Authors: Chen Zefeng , Chen Xuequan , Tao Li , Chen Kun , Long Mingzhu , Liu Xudong , Yan Keyou , Stantchev Rayko I. , Pickwell-MacPherson Emma , Xu Jian-Bin
Published: November 2018

Terahertz modulators with high tunability of both intensity and phase are essential for effective control of electromagnetic properties. Due to the underlying physics behind existing approaches there is still a lack of broadband devices able to achieve deep modulation. Here, we demonstrate the effect of tunable Brewster angle controlled by graphene, and develop a highly-tunable solid-state graphene/quartz modulator based on this mechanism. The Brewster angle of the device can be tuned by varying the conductivity of the graphene through an electrical gate. In this way, we achieve near perfect intensity modulation with spectrally flat modulation depth of 99.3 to 99.9 percent and phase tunability of up to 140 degree in the frequency range from 0.5 to 1.6 THz. Different from using electromagnetic resonance effects (for example, metamaterials), this principle ensures that our device can operate in ultra-broadband. Thus it is an effective principle for terahertz modulation.
The Trans Golgi Region is a Labile Intracellular Ca2+ Store Sensitive to Emetine
Authors: Gallegos-Gómez Martín-Leonardo , Greotti Elisa , López-Méndez María-Cristina , Sánchez-Vázquez Víctor-Hugo , Arias Juan-Manuel , Guerrero-Hernández Agustín
Published: November 2018

The Golgi apparatus (GA) is a bona fide Ca2+ store; however, there is a lack of GA-specific Ca2+ mobilizing agents. Here, we report that emetine specifically releases Ca2+ from GA in HeLa and HL-1 atrial myocytes. Additionally, it has become evident that the trans-Golgi is a labile Ca2+ store that requires a continuous source of Ca2+ from either the external milieu or from the ER, to enable it to produce a detectable transient increase in cytosolic Ca2+. Our data indicates that the emetine-sensitive Ca2+ mobilizing mechanism is different from the two classical Ca2+ release mechanisms, i.e. IP3 and ryanodine receptors. This newly discovered ability of emetine to release Ca2+ from the GA may explain why chronic consumption of ipecac syrup has muscle side effects.
Deterioration of willow seeds during storage
Authors: López-Fernández María Paula , Moyano Laura , Correa María Daniela , Vasile Franco , Burrieza Hernán Pablo , Maldonado Sara
Published: November 2018

Willow (Salix spp.) seeds are able to tolerate desiccation, but differ from typical orthodox seeds in that they lose viability in a few days at room temperature, and in that the chloroplasts in embryo tissues do not dedifferentiate during maturation drying, thus retaining chlorophyll and maintaining intact their thylakoid membranes. In the present study, we investigated the damage generated in willow seeds during storage under appropriate conditions to exclude the eventual generation of reactive oxygen species by photooxidation. To this end, we measured different indicators of molecular damage, such as changes in the fatty acid profile, protein degradation, nuclease activities, and DNA damage, and evaluated normal germination and total germination in seeds stored for one, ten and sixteen years. We found: (i) a decrease in the fraction of unsaturated fatty acids; (ii) changes in the protein profile due to a decrease in protein solubility; (iii) activation of nucleases; and (iv) DNA fragmentation. Taken together, our findings identified programmed cell death as a key mechanism in seed deterioration during storage. We also found that, although the seeds maintained high percentages of total germination, the death program had already started in the seeds stored for ten years and was more advanced in those stored for sixteen years.
Optical coherence tomography angiography analysis of changes in the retina and the choroid after haemodialysis
Authors: Shin Yong Un , Lee Dong Eik , Kang Min Ho , Seong Mincheol , Yi Joo-Hark , Han Sang-Woong , Cho Heeyoon
Published: November 2018

The purpose of this study is to evaluate the effect of haemodialysis on perfused vessel density, choroidal thickness (CT), and retinal thickness in end-stage renal disease (ESRD) using swept-source optical coherence tomography angiography (SS-OCTA). We studied twenty-nine eyes of 29 ESRD patients by ophthalmologic examination and SS-OCTA before and after haemodialysis. The colour-coded perfusion density maps were generated and perfused vessel density was calculated. Changes in systemic and other ocular parameters such as retinal and choroidal thickness were measured and analysed. Total perfused vessel density decreased significantly after haemodialysis in the choriocapillaris; it was not significantly different in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Total CT decreased significantly, but total retinal thickness was not significantly different. There was no significant correlation between choriocapillaris perfused vessel density and CT. The reduction in choriocapillaris perfused vessel density correlated with the decrease in systolic and mean arterial blood pressures. The decrease in CT correlated with the ultrafiltration volume. There were no significant systemic and ocular factors affecting change in retinal thickness and perfused vessel density of SCP and DCP. This is the first study to assess the effect of haemodialysis on blood flow changes using SS-OCTA; changes may be more prominent in the choroidal compared to the retinal layer.
Author Correction: Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages
Authors: Hu Lulu , Hu Xiaomin , Long Kai , Gao Chenhui , Dong Hong-Liang , Zhong Qiao , Gao Xiao-Ming , Gong Fang-Yuan
Published: November 2018

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 split luciferase-based probe for quantitative proximal determination of Gαq signalling in live cells
Authors: Littmann Timo , Ozawa Takeaki , Hoffmann Carsten , Buschauer Armin , Bernhardt Günther
Published: November 2018

The earlier an activation of a G protein-dependent signalling cascade at a G protein-coupled receptor (GPCR) is probed, the less amplificatory effects contribute to the measured signal. This is especially useful in case of a precise quantification of agonist efficacies, and is of paramount importance, when determining agonist bias in relation to the β-arrestin pathway. As most canonical assays with medium to high throughput rely on the quantification of second messengers, and assays affording more proximal readouts are often limited in throughput, we developed a technique with a proximal readout and sufficiently high throughput that can be used in live cells. Split luciferase complementation (SLC) was applied to assess the interaction of Gαqwith its effector phospholipase C-β3. The resulting probe yielded an excellent Z’ value of 0.7 and offers a broad and easy applicability to various Gαq-coupling GPCRs (hH1R, hM1,3,5R, hNTS1R), expressed in HEK293T cells, allowing the functional characterisation of agonists and antagonists. Furthermore, the developed sensor enabled imaging of live cells by luminescence microscopy, as demonstrated for the hM3R. The versatile SLC-based probe is broadly applicable e.g. to the screening and the pharmacological characterisation of GPCR ligands as well as to molecular imaging.
Digital mapping and spatial characteristics analyses of heavy metal content in reclaimed soil of industrial and mining abandoned land
Authors: Zhang Shiwen , Liu Huilin , Luo Ming , Zhou Xu , Lei Mei , Huang Yuanfang , Zhou Yan , Ge Chang
Published: November 2018

The reclaimed soil properties of industrial and mining wasteland have strong spatial specificity. The paper aimed to screen out a hybrid multifractal and kriging (Named as Mkriging) method for digital mapping and scientifically reveal the spatial distribution characteristics in view of heavy metal in reclaimed soil of industrial and mining abandoned land. The results of the study showed that for reasons of history and reclamation, the original samples of heavy metals in reclaimed soil of industrial and mining abandoned land showed a very large range and variation degree, theC0/(C0 + C1) values of different heavy metals basically were all greater than 50%, random factors played a dominant role. The five kinds of heavy metals in reclaimed soil were in the following descending order in terms of homogeneity: Cd, As, Hg, Ni and Cr. Compared with ordinary Kriging method, the relative improvement of root mean squared errors of elements Cd, Hg, As, Cr and Ni based on Mkriging were 95.28%, 61.74%, 78.54%, 82.51% and 83.58% respectively. The higher the fractal degree of heavy metals in reclaimed soil was, the higher the prediction accuracy will be. Mkriging method is more suitable for spatial prediction of heavy metals in reclaimed soil of industrial and mining abandoned land.