bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint ambient noise autocorrelation and receiver function analysis of the Moho
Authors: Mroczek Stefan , Tilmann Frederik
Published: February 2021

In the field of seismic interferometry, cross-correlations are used to extract Green’s function from ambient noise data. By applying a single station variation of the method, using autocorrelations, we are in principle able to retrieve zero-offset reflections in a stratified Earth. These reflections are valuable as they do not require an active seismic source and, being zero-offset, are better constrained in space than passive earthquake based measurements. However, studies that target Moho signals with ambient noise autocorrelations often give ambiguous results with unclear Moho reflections. Using a modified processing scheme and phase-weighted stacking, we determine the Moho P-wave reflection time from vertical autocorrelation traces for a test station with a known simple crustal structure (HYB in Hyderabad, India). However, in spite of the simplicity of the structure, the autocorrelation traces show several phases not related to direct reflections. Although we are able to match some of these additional phases in a qualitative way with synthetic modelling, their presence makes it hard to identify the reflection phases without prior knowledge. This prior knowledge can be provided by receiver functions. Receiver functions (arising from mode conversions) are sensitive to the same boundaries as autocorrelations, so should have a high degree of comparability and opportunity for combined analysis but in themselves are not able to independently resolve VP, VS and Moho depth. Using the timing suggested by the receiver functions as a guide, we observe the Moho S-wave reflection on the horizontal autocorrelation of the north component but not on the east component. The timing of the S reflection is consistent with the timing of the PpSs–PsPs receiver function multiple, which also depends only on the S velocity and Moho depth. Finally, we combine P receiver functions and autocorrelations from HYB in a depth–velocity stacking scheme that gives us independent estimates for VP, VS and Moho depth. These are found to be in good agreement with several studies that also supplement receiver functions to obtain unique crustal parameters. By applying the autocorrelation method to a portion of the EASI transect crossing the Bohemian Massif in central Europe, we find approximate consistency with Moho depths determined from receiver functions and spatial coherence between stations, thereby demonstrating that the method is also applicable for temporary deployments. Although application of the autocorrelation method requires great care in phase identification, it has the potential to resolve both average crustal P and S velocities alongside Moho depth in conjunction with receiver functions.
A retrospective ‘real-world’ cohort study of azole therapeutic drug monitoring and evolution of antifungal resistance in cystic fibrosis
Authors: Di Paolo M , Hewitt L , Nwankwo E , Ni M , Vidal-Diaz A , Fisher M C , Armstrong-James D , Shah A
Published: February 2021

Background

Individuals with cystic fibrosis (CF) have an increased susceptibility to fungal infection/allergy, with triazoles often used as first-line therapy. Therapeutic drug monitoring (TDM) is essential due to significant pharmacokinetic variability and the recent emergence of triazole resistance worldwide.

Objectives

In this retrospective study we analysed the ‘real-world’ TDM of azole therapy in a large CF cohort, risk factors for subtherapeutic dosing, and the emergence of azole resistance.

Methods

All adults with CF on azole therapy in a large single UK centre were included. Clinical demographics, TDM and microbiology were analysed over a 2 year study period (2015–17) with multivariate logistic regression used to identify risk factors for subtherapeutic dosing.

Results

91 adults were treated with azole medication during the study period. A high prevalence of chronic subtherapeutic azole dosing was seen with voriconazole (60.8%) and itraconazole capsule (59.6%) use, representing significant risk factors for subtherapeutic levels. Rapid emergence of azole resistance was additionally seen over the follow-up period with a 21.4% probability of CF patients developing a resistant fungal isolate after 2 years. No significant relationship was found however between subtherapeutic azole dosing and azole resistance emergence.

Conclusions

Our study demonstrates a high prevalence of subtherapeutic azole levels in CF adults with increased risk using itraconazole capsules and voriconazole therapy. We show rapid emergence of azole resistance highlighting the need for effective antifungal stewardship. Further large longitudinal studies are needed to understand the effects of antifungal resistance on outcome in CF and the implications of subtherapeutic dosing on resistance evolution.
Antimicrobial stewardship of antiseptics that are pertinent to wounds: the need for a united approach
Authors: Maillard Jean-Yves , Kampf Günter , Cooper Rose
Published: February 2021

Long before the nature of infection was recognized, or the significance of biofilms in delayed healing was understood, antimicrobial agents were being used in wound care. In the last 70 years, antibiotics have provided an effective means to control wound infection, but the continued emergence of antibiotic-resistant strains and the documented antibiotic tolerance of biofilms has reduced their effectiveness. A range of wound dressings containing an antimicrobial (antibiotic or non-antibiotic compound) has been developed. Whereas standardized methods for determining the efficacy of non-antibiotic antimicrobials in bacterial suspension tests were developed in the early twentieth century, standardized ways of evaluating the efficacy of antimicrobial dressings against microbial suspensions and biofilms are not available. Resistance to non-antibiotic antimicrobials and cross-resistance with antibiotics has been reported, but consensus on breakpoints is absent and surveillance is impossible. Antimicrobial stewardship is therefore in jeopardy. This review highlights these difficulties and in particular the efficacy of current non-antibiotic antimicrobials used in dressings, their efficacy, and the challenges of translating in vitro efficacy data to the efficacy of dressings in patients. This review calls for a unified approach to developing standardized methods of evaluating antimicrobial dressings that will provide an improved basis for practitioners to make informed choices in wound care.
Clinical data sharing improves quality measurement and patient safety
Authors: D’Amore John D , McCrary Laura K , Denson Jody , Li Chun , Vitale Christopher J , Tokachichu Priyaranjan , Sittig Dean F , McCoy Allison B , Wright Adam
Published: February 2021

Objective

Accurate and robust quality measurement is critical to the future of value-based care. Having incomplete information when calculating quality measures can cause inaccuracies in reported patient outcomes. This research examines how quality calculations vary when using data from an individual electronic health record (EHR) and longitudinal data from a health information exchange (HIE) operating as a multisource registry for quality measurement.

Materials and Methods

Data were sampled from 53 healthcare organizations in 2018. Organizations represented both ambulatory care practices and health systems participating in the state of Kansas HIE. Fourteen ambulatory quality measures for 5300 patients were calculated using the data from an individual EHR source and contrasted to calculations when HIE data were added to locally recorded data.

Results

A total of 79% of patients received care at more than 1 facility during the 2018 calendar year. A total of 12 994 applicable quality measure calculations were compared using data from the originating organization vs longitudinal data from the HIE. A total of 15% of all quality measure calculations changed (P < .001) when including HIE data sources, affecting 19% of patients. Changes in quality measure calculations were observed across measures and organizations.

Discussion

These results demonstrate that quality measures calculated using single-site EHR data may be limited by incomplete information. Effective data sharing significantly changes quality calculations, which affect healthcare payments, patient safety, and care quality.

Conclusions

Federal, state, and commercial programs that use quality measurement as part of reimbursement could promote more accurate and representative quality measurement through methods that increase clinical data sharing.
Effects of administering exogenous bovine somatotropin to beef heifers during the first trimester on conceptus development as well as steroid- and eicosanoid-metabolizing enzymes
Authors: Sanford Carla D , Owen Megan P T , Oosthuizen Nicola , Fontes Pedro L P , Vonnahme Kimberly A , Nelson Megan , Reyaz Arshi , Lemley Caleb O , DiLorenzo Nicolas , Cliff Lamb Graham
Published: February 2021

The aim of this study was to evaluate the effect of bovine somatotropin (bST) on fetal and placental development during the first third of gestation in beef heifers. Angus heifers (n = 97) were randomly assigned to either receive a 500-mg injection of bST (BST) biweekly on days 0, 15, 29, 43, and 57 of gestation or not receive bST (CTL) throughout the experiment. Body weight (BW) was assessed on days −9, −3, 0, 15, 22, 29, 43, 50, 57, 64, and 77, while blood samples were collected on days 0, 22, 50, and 64. Pregnancy status was determined via transrectal ultrasonography on days 29 and 64. A subset of pregnant heifers (BST, n = 7; CTL, n = 5) were harvested on day 84, and complete gravid reproductive tracts and liver tissue were collected for analysis. Cytochrome P450 1A (CYP1A), 2C (CYP2C), 3A (CYP3A), and uridine 5′-diphospho-glucuronosyltransferase (UGT) activities were determined. Mean change in BW and average daily gain of heifers between fixed-time artificial insemination (day 0) and day 77 did not differ between treatments (P ≥ 0.05). Mean concentrations of insulin-like growth factor 1 (IGF-1) were greater (P < 0.001) in BST (347 ± 27.7 ng/mL) compared with CTL (135 ± 32.8 ng/mL) heifers. Mean placental weight, fetal membrane weight, uterine weight, and ovarian and corpus luteum (CL) weights, as well as fetal morphometric data, did not differ (P ≥ 0.05) between treatments. However, BST heifers had greater (P = 0.03) quantities of combined fetal fluid compared with CTL (521.6 ± 22.9 vs. 429.6 ± 27.14 g, respectively). Tendencies were observed for BST heifers to have reproductive tracts with fewer placentomes (P = 0.08) and fetuses with greater umbilical diameters (P = 0.09) compared with CTL. The activity of CYP1A did not differ (P ≥ 0.05) within the maternal and fetal liver, caruncle, cotyledon, or CL tissue samples between treatments. Furthermore, CYP3A activity was only observed in maternal liver samples and was not different between treatments (P ≥ 0.05). Interestingly, CYP2C activity was greater (P = 0.01) in the liver of BST vs. CTL heifers, and UGT activity was greater (P = 0.02) in the CL from BST heifers compared with CTL. In conclusion, the administration of bST during the first third of gestation increased plasma concentrations of IGF-1, which resulted in an increase in fetal fluid, decrease in placentome number, and greater umbilical diameter, but failed to alter fetal development.
Economic and environmental assessments of combined genetics and nutrition optimization strategies to improve the efficiency of sustainable pork production
Authors: Soleimani Tara , Hermesch Susanne , Gilbert Hélène
Published: February 2021

We evaluated the economic and environmental impacts of strategies that incorporated selection for pig feed efficiency and dietary optimization based on a single or multiple objectives tailored to meet the population nutritional requirements, with the goal to optimize sustainable farm feed efficiency. The economic and environmental features of the strategy were evaluated using life cycle assessment (LCA) and bio-economic models. An individual trait-based LCA model was applied to evaluate global warming potential, terrestrial acidification potential, freshwater eutrophication potential (EP), and land occupation of the combined genetics and nutrition optimization to produce 1 kg of live pig weighing 120 kg at the farm gate. A parametric individual trait-based bio-economic model was developed and applied to determine the cost breakdown, revenue, and profit to be gained from a 120-kg live pig at the farm gate. Data from two genetic lines with contrasted levels of feed efficiency were used to apply the combined genetics and nutrition optimization: accounting for the average nutritional requirements for each line, the individual pig responses to diets formulated for least cost, least environmental impacts, or minimum combination of costs and environmental impacts objectives were predicted with INRAPorc. Significant differences in the environmental impacts (P < 0.0001) and profit (P < 0.05) between lines predicted with the same reference diet showed that selection for feed efficiency (residual feed intake) in pigs improves pig production sustainability. When pig responses were simulated with their line-optimized diets, except for EP, all the line environmental impacts were lower (P < 0.05) than with the reference diet. The high correlations of feed conversion ratio with the environmental impacts (> 0.82) and the profit (< −0.88) in both lines underlined the importance of feed efficiency as a lever for the sustainability of pig production systems. Implementing combined genetics and nutrition optimization, the inherent profit and environmental differences between the genetic lines were predicted to be reduced from 23.4% with the reference diet to 7.6% with the diet optimized jointly for economic and environmental objectives (joint diet). Consequently, for increased pig sustainability, diet optimization for sustainability objectives should be applied to cover the specific nutritional requirements arising in the herd from the pigs genetic level.
Validating the effectiveness of alternative euthanasia techniques using penetrating captive bolt guns in mature swine (Sus scrofa domesticus)
Authors: Kramer Scott A , Wagner Brooklyn K , Robles Ivelisse , Moeller Steve J , Bowman Andrew S , Kieffer Justin D , Arruda Andréia Gonçalves , Cressman Michael D , Pairis-Garcia Monique D
Published: February 2021

Euthanasia of mature swine is challenging. Temporal and behind-the-ear locations are two sites that have been identified as alternatives to the more commonly used frontal placement. In stage one, the effectiveness of two penetrating captive bolt gun styles (cylinder or pistol) was evaluated using frontal, temporal, and behind-the-ear placement in anesthetized mature swine (n = 36; weight: 267 ± 41 kg). For stage one, when evaluating treatment efficacy by sex, the cylinder-style equipment was 100% effective in achieving death when applied to all cranial locations (frontal, temporal, and behind-the-ear) for sows; however, the pistol-style equipment was only 100% effective when applied at the behind-the-ear location for sows. For boars, the cylinder-style equipment was 100% effective when applied to the frontal and behind-the-ear location, but the pistol-style equipment was not effective for any cranial location in boars. Therefore, the pistol–frontal, pistol–temporal, pistol–behind-the-ear, and cylinder–temporal were not included for boars, and pistol–frontal and pistol–temporal were not included for sows in stage two. In stage two, commercial, mixed-breed, mature swine (n = 42; weight: 292 +/− 56 kg) were randomly assigned to one of four treatments based on the inclusion criteria described in stage one. A three-point traumatic brain injury (TBI) score (0 = normal; 1 = some abnormalities; 2 = grossly abnormal, unrecognizable) was used to evaluate six neuroanatomical structures (cerebral cortex, cerebellum, hypothalamus, thalamus, pons, and brain stem), and the presence of hemorrhage was also noted. All treatments were 100% effective in stage two. A significant interaction between gun style and placement was determined on predicting total TBI as the cylinder style produced a higher total TBI score compared with the pistol type of the magnitude of +2.8 (P < 0.01). The cylinder style tended to produce a greater TBI score than the pistol in the temporal location (+1.2; P = 0.08). No difference was noted for TBI score behind-the-ear between the cylinder- and pistol-style gun (P > 0.05). TBI tended to be less in boars compared with sows (−0.6; P = 0.08). Hemorrhage was observed in frontal, parietal, occipital, and temporal lobes. This study demonstrated that the cylinder-style captive bolt gun more effectively resulted in brain trauma and death compared with a pistol-style gun and the behind-the-ear and temporal placement showed promise as an alternative placement site for euthanizing mature pigs on-farm.
Frozen in the dark: interplay of night-time activity of xanthophyll cycle, xylem attributes, and desiccation tolerance in fern resistance to winter
Authors: Fernández-Marín Beatriz , Arzac Miren Irati , López-Pozo Marina , Laza José Manuel , Roach Thomas , Stegner Matthias , Neuner Gilbert , García-Plazaola José I
Published: February 2021

While most ferns avoid freezing as they have a tropical distribution or shed their fronds, wintergreen species in temperate and boreoalpine ecosystems have to deal with sub-zero temperatures. Increasing evidence has revealed overlapping mechanisms of desiccation and freezing tolerance in angiosperms, but the physiological mechanisms behind freezing tolerance in ferns are far from clear. We evaluated photochemical and hydraulic parameters in five wintergreen fern species differing in their ability to tolerate desiccation. We assessed frond freezing tolerance, ice nucleation temperature and propagation pattern, and xylem anatomical traits. Dynamics of photochemical performance and xanthophyll cycle were evaluated during freeze–thaw events under controlled conditions and, in selected species, in the field. Only desiccation-tolerant species, which possessed a greater fraction of narrow tracheids (<18 μm) than sensitive species, tolerated freezing. Frond freezing occurred in the field at –3.4 ± 0.9 °C (SD) irrespective of freezing tolerance, freezable water content, or tracheid properties. Even in complete darkness, maximal photochemical efficiency of photosystem II was down-regulated concomitantly with zeaxanthin accumulation in response to freezing. This was reversible upon re-warming only in tolerant species. Our results suggest that adaptation for freezing tolerance is associated with desiccation tolerance through complementary xylem properties (which may prevent risk of irreversible cavitation) and effective photoprotection mechanisms. The latter includes de-epoxidation of xanthophylls in darkness, a process evidenced for the first time directly in the field.
A temperature regime that disrupts clock-controlled starch mobilization induces transient carbohydrate starvation, resulting in compact growth
Authors: van Hoogdalem Mark , Shapulatov Umidjon , Sergeeva Lidiya , Busscher-Lange Jacqueline , Schreuder Mariëlle , Jamar Diaan , van der Krol Alexander R
Published: February 2021

In nature, plants are usually subjected to a light/temperature regime of warm days and cold nights (referred to as +DIF). Compared with growth under +DIF, Arabidopsis plants show compact growth under the same photoperiod, but with an inverse temperature regime (cold days and warm nights: –DIF). Here we show that –DIF differentially affects the phase and amplitude of core clock gene expression. Under –DIF, the phase of the morning clock gene CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) is delayed, similar to that of plants grown on low sucrose. Indeed, under –DIF, carbohydrate (CHO) starvation marker genes are specifically up-regulated at the end of the night (EN) in Arabidopsis rosettes. However, only in inner rosette tissue (small sink leaves and petioles of older leaves) are sucrose levels lower under –DIF compared with under +DIF, suggesting that sucrose in source leaf blades is not sensed for CHO status and that sucrose transport from source to sink may be impaired at EN. CHO starvation under –DIF correlated with increased starch breakdown during the night and decreased starch accumulation during the day. Moreover, we demonstrate that different ways of inducing CHO starvation all link to reduced growth of sink leaves. Practical implications for control of plant growth in horticulture are discussed.
Characterizing outflows in the Cygnus X region
Authors: Deb Soumen , Kothes Roland , Rosolowsky Erik
Published: February 2021

In this paper, we perform an analysis of 13 outflows in the Cygnus X star-forming region. We use the James Clerk Maxwell Telescope observations of 13CO(3–2) and C18O(3–2) molecular emission lines combined with archival 12CO(3–2) data. Using these new observations, we measure the mechanical properties of the outflows, and identify the associated protostars, finding their properties consistent with previous surveys of outflows throughout the Milky Way. Finally, we develop and test a method to measure the same properties using the existing 12CO(3–2) line data alone, finding the properties agree to within a factor of 2.
Limits on the presence of planets in systems with debris discs: HD 92945 and HD 107146
Authors: Mesa D , Marino S , Bonavita M , Lazzoni C , Fontanive C , Pérez S , D’Orazi V , Desidera S , Gratton R , Engler N , Henning T , Janson M , Kral Q , Langlois M , Messina S , Milli J , Pawellek N , Perrot C , Rigliaco E , Rickman E , Squicciarini V , Vigan A , Wahhaj Z , Zurlo A , Boccaletti A , Bonnefoy M , Chauvin G , De Caprio V , Feldt M , Gluck L , Hagelberg J , Keppler M , Lagrange A-M , Launhardt R , Maire A-L , Meyer M , Moeller-Nilsson O , Pavlov A , Samland M , Schmidt T , Weber L
Published: February 2021

Recent observations of resolved cold debris discs at tens of au have revealed that gaps could be a common feature in these Kuiper-belt analogues. Such gaps could be evidence for the presence of planets within the gaps or closer in near the edges of the disc. We present SPHERE observations of HD 92945 and HD 107146, two systems with detected gaps. We constrained the mass of possible companions responsible for the gap to 1–2 MJup for planets located inside the gap and to less than 5 MJup for separations down to 20 au from the host star. These limits allow us to exclude some of the possible configurations of the planetary systems proposed to explain the shape of the discs around these two stars. In order to put tighter limits on the mass at very short separations from the star, where direct-imaging data are less effective, we also combined our data with astrometric measurements from Hipparcos and Gaia and radial-velocity measurements. We were able to limit the separation and the mass of the companion potentially responsible for the proper-motion anomaly of HD 107146 to values of 2–7 au and 2–5 MJup, respectively.
The Impact of Purifying and Background Selection on the Inference of Population History: Problems and Prospects
Authors: Johri Parul , Riall Kellen , Becher Hannes , Excoffier Laurent , Charlesworth Brian , Jensen Jeffrey D.
Published: February 2021

Current procedures for inferring population history generally assume complete neutrality—that is, they neglect both direct selection and the effects of selection on linked sites. We here examine how the presence of direct purifying selection and background selection may bias demographic inference by evaluating two commonly-used methods (MSMC and fastsimcoal2), specifically studying how the underlying shape of the distribution of fitness effects and the fraction of directly selected sites interact with demographic parameter estimation. The results show that, even after masking functional genomic regions, background selection may cause the mis-inference of population growth under models of both constant population size and decline. This effect is amplified as the strength of purifying selection and the density of directly selected sites increases, as indicated by the distortion of the site frequency spectrum and levels of nucleotide diversity at linked neutral sites. We also show how simulated changes in background selection effects caused by population size changes can be predicted analytically. We propose a potential method for correcting for the mis-inference of population growth caused by selection. By treating the distribution of fitness effect as a nuisance parameter and averaging across all potential realizations, we demonstrate that even directly selected sites can be used to infer demographic histories with reasonable accuracy.
Pulmonary findings on high-resolution computed tomography in Takayasu arteritis
Authors: Kong Xiufang , Zhang Jing , Lin Jiang , Lv Peng , Chen Huiyong , Ji Zongfei , Dai Xiaomin , Jin Xuejuan , Ma Lili , Jiang Lindi
Published: February 2021

Objective

This study aimed to describe pulmonary high-resolution CT (HRCT) findings in Takayasu arteritis (TA) and to determine possible causes.

Methods

A total of 243 TA patients were enrolled from a prospective cohort after excluding patients with other pulmonary disorders or incomplete data. Patients were divided into two groups: those with normal lung HRCT and those with abnormal lung HRCT. Clinical characteristics were compared between groups and binary logistic regression analysis was applied to identify possible causes of the lung lesions. Follow-up HRCT (obtained in 64 patients) was analysed to study changes in pulmonary lesions after treatment.

Results

Of the 243 patients, 107 (44.0%) had normal lung HRCT while 136 (56.0%) had abnormal lung HRCT, including stripe opacity (60.3%), nodules (44.9%), patchy opacity (25.0%), pleural thickening (15.4%), pleural effusion (10.3%), ground-glass opacity (8.1%), pulmonary infarction (6.6%), mosaic attenuation (4.4%), bronchiectasis (3.7%) and pulmonary oedema (2.2%). Patients with abnormal HRCT were significantly more likely to have type II arterial involvement (25% vs 12.2%, P = 0.04), pulmonary arterial involvement (PAI; 21.3% vs 5.6%, P < 0.001), pulmonary hypertension (20.6% vs 8.4%, P = 0.01) and abnormal heart function (27.9% vs 7.6%, P < 0.001). Logistic regression analysis demonstrated that PAI, worsened heart function and age were associated with presence of pulmonary lesions. Pulmonary infarction, pleural effusion and patchy opacities improved partially after treatment.

Conclusion

Pulmonary lesions are not rare in patients with TA. Age, PAI and worsened heart function are potential risk factors for presence of pulmonary lesions in TA.
CO2 refixation is higher in leaves of woody species with high mesophyll and stomatal resistances to CO2 diffusion
Authors: Eckert Diana , Martens Helle Juel , Gu Lianhong , Jensen Anna Monrad
Published: February 2021

The percentage of respiratory and photorespiratory CO2 refixed in leaves (Pr) represents part of the CO2 used in photosynthesis. The importance of Pr as well as differences between species and functional types are still not well investigated. In this study, we examine how Pr differs between six temperate and boreal woody species: Betula pendula, Quercus robur, Larix decidua, Pinus sylvestris, Picea abies and Vaccinium vitis-idaea. The study covers early and late successional species, deciduous broadleaves, deciduous conifers, evergreen conifers and evergreen broadleaves. We investigated whether some species or functional types had higher refixation percentages than others, whether leaf traits could predict higher Pr and whether these traits and their impact on Pr changed during growing seasons. Photosynthesis CO2 response (A/Ci)-curves, measured early, mid and late season, were used to estimate and compare Pr, mesophyll resistance (rm) and stomatal resistance (rs) to CO2 diffusion. Additionally, light images and transmission electron microscope images were used to approximate the fraction of intercellular airspace and cell wall thickness. We found that evergreens, especially late successional species, refixed a significantly higher amount of CO2 than the other species throughout the entire growing season. In addition, rm, rs and leaf mass per area, traits that typically are higher in evergreen species, were also significantly, positively correlated with Pr. We suggest that this is due to higher rm decreasing diffusion of (photo) respiratory CO2 out of the leaf. Cell wall thickness had a positive effect on Pr and rm, while the fraction of intercellular airspace had no effect. Both were significantly different between evergreen conifers and other types. Our findings suggest that species with a higher rm use a greater fraction of mitochondria-derived CO2, especially when stomatal conductance is low. This should be taken into account when modeling the overall CO2 fertilization effect for terrestrial ecosystems dominated by high rm species.
A comprehensive profile of genomic variations in the SARS-CoV-2 isolates from the state of Telangana, India
Authors: Gupta Asmita , Sabarinathan Radhakrishnan , Bala Pratyusha , Donipadi Vinay , Vashisht Divya , Katika Madhumohan Rao , Kandakatla Manohar , Mitra Debashis , Dalal Ashwin , Bashyam Murali Dharan
Published: February 2021

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has rapidly turned into a pandemic, infecting millions and causing 1 157 509 (as of 27 October 2020) deaths across the globe. In addition to studying the mode of transmission and evasion of host immune system, analysing the viral mutational landscape constitutes an area under active research. The latter is expected to impart knowledge on the emergence of different clades, subclades, viral protein functions and protein–protein and protein–RNA interactions during replication/transcription cycle of virus and response to host immune checkpoints. In this study, we have attempted to bring forth the viral genomic variants defining the major clade(s) as identified from samples collected from the state of Telangana, India. We further report a comprehensive draft of all genomic variations (including unique mutations) present in SARS-CoV-2 strain in the state of Telangana. Our results reveal the presence of two mutually exclusive subgroups defined by specific variants within the dominant clade present in the population. This work attempts to bridge the critical gap regarding the genomic landscape and associate mutations in SARS-CoV-2 from a highly infected southern region of India, which was lacking to date.
Effect of ozone exposure on Amyotrophic Lateral Sclerosis (ALS) pathology using a mice model of TDP-43 proteinopathy
Authors: Rodriguez Ana , Ferrer-Donato Agueda , Cabrera-Pinto Marta , Seseña Susana , Fernández Paloma , Aranda Alfonso , Fernandez-Martos Carmen M.
Published: February 2021

Background

Ozone (O3), one of the main photochemical pollutants in the atmosphere today, is a serious health risk factor. Although the effects of O3exposure have been documented on many diseases, they have not yet been examined on Amyotrophic Lateral Sclerosis (ALS)- a fatal progressive and neurodegenerative disease.

Objectives

To investigate the effect of the O3exposure in a mice model of TDP-43 proteinopathy, exploring a possible association between the O3exposure and the ALS pathogenesis.

Methods

TDP-43A315Tand wild-type (WT) mice were exposed to O3(0.25 ppm) or filtered air (FA) for 15 days (4 hours/day). We assessed (1) weight loss (2) motor performance (3) plasma glucose content and (4) metabolic markers from plasma samples of the animals.

Results

Throughout the experiment, we observed a progressive decline in body weight and the motor coordination in TDP-43A315Tmice compared to WT controls. Although there was a trend, there were no significant differences in the decline of body weight of TDP-43A315Tmice when exposed to either FA or O3. In O3-TDP-43A315Tmice, the disease duration lasted longer. In addition, O3-TDP-43A315Tmice showed improvements in motor performance as well TDP-43A315Tmice were hypoglycemic compared to WT mice. However, FA-TDP-43A315Tmice showed lower plasma glucose levels at the disease end-stage. We found altered levels of adipokines and metabolic proteins in TDP-43A315Tmice compared to WT controls. A positive correlation was found among GIP and glucagon compared to insulin concentrations in control mice. Interestingly, resistin, Gastric Inhibitory Peptide (GIP), Glucagon Like Peptide 1 (GIP-1) and insulin levels were higher in O3-TDP-43A315Tmice.

Discussion

We provide new evidence about a mechanistic link between O3exposure and the improvement of the metabolic disturbances present in TDP-43A315Tmice. Further studies are needed to corroborate the obtained results as they warrant to understanding the underlying mechanisms.
DLAB - Deep learning methods for structure-based virtual screening of antibodies
Authors: Schneider Constantin , Buchanan Andrew , Taddese Bruck , Deane Charlotte M.
Published: February 2021

Antibodies are one of the most important classes of pharmaceuticals, with over 80 approved molecules currently in use against a wide variety of diseases. The drug discovery process for antibody therapeutic candidates however is time-and cost-intensive and heavily reliant onin-vivoandin-vitrohigh throughput screens. Here, we introduce a framework for structure-based deep learning for antibodies (DLAB) which can virtually screen putative binding antibodies against antigen targets of interest. DLAB is built to be able to predict antibody-antigen binding for antigens with no known antibody binders.

We demonstrate that DLAB can be used both to improve antibody-antigen docking and structure-based virtual screening of antibody drug candidates. DLAB enables improved pose ranking for antibody docking experiments as well as selection of antibody-antigen pairings for which accurate poses are generated and correctly ranked. We also show that DLAB can identify binding antibodies against specific antigens in a case study. Our results demonstrate the promise of deep learning methods for structure-based virtual screening of antibodies.
Integument transcriptome profile of the European sea cucumberHolothuria forskali (Holothuroidea, Echinodermata)
Authors: Delroisse Jérôme , Bonneel Marie , Demeuldre Mélanie , Eeckhaut Igor , Flammang Patrick
Published: February 2021

In non-model organisms, Next Generation Sequencing (NGS) technology improve our ability to analyze gene expression and identify new genes or transcripts of interest. In this research, paired-end Illumina HiSeq sequencing has been used to describe a composite transcriptome based on two libraries generated from dorsal and ventral integuments of the European sea cucumberHolothuria forskali (Holothuroidea, Echinodermata). A total of 43,044,977 million HQ reads were initially generated. Afterde novoassembly, a total of 111,194 unigenes were predicted. On all predicted unigenes, 32,569 show significant matches with genes/proteins present in the reference databases. Around 50% of annotated unigenes were significantly similar to sequences from the purple sea urchinStrongylocentrotus purpuratusgenome. Annotation analyses were performed on predicted unigenes using public reference databases. These RNA-seq data provide an interesting resource for researchers with a broad interest in sea cucumber biology.
Penalized Logistic Regression Analysis for Genetic Association Studies of Binary Phenotypes
Authors: Yu Ying , Chen Siyuan , Jones Samantha J. , Hoque Rawnak , Vishnyakova Olga , Brooks-Wilson Angela , McNeney Brad
Published: February 2021

Introduction

Increasingly, logistic regression methods for genetic association studies of binary phenotypes must be able to accommodate data sparsity, which arises from unbalanced case-control ratios and/or rare genetic variants. Sparseness leads to maximum likelihood estimators (MLEs) of log-OR parameters that are biased away from their null value of zero and tests with inflated type 1 errors. Different penalized-likelihood methods have been developed to mitigate sparse-data bias. We study penalized logistic regression using a class of log-Fpriors indexed by a shrinkage parametermto shrink the biased MLE towards zero.

Methods

We propose a two-step approach to the analysis of a genetic association study: first, a set of variants that show evidence of association with the trait is used to estimatem; and second, the estimatedmis used for log-F-penalized logistic regression analyses of all variants using data augmentation with standard software. Our estimate ofmis the maximizer of a marginal likelihood obtained by integrating the latent log-ORs out of the joint distribution of the parameters and observed data. We consider two approximate approaches to maximizing the marginal likelihood: (i) a Monte Carlo EM algorithm (MCEM) and (ii) a Laplace approximation (LA) to each integral, followed by derivative-free optimization of the approximation.

Results

We evaluate the statistical properties of our proposed two-step method and compared its performance to other shrinkage methods by a simulation study. Our simulation studies suggest that the proposed log-F-penalized approach has lower bias and mean squared error than other methods considered. We also illustrate the approach on data from a study of genetic associations with “super senior” cases and middle aged controls.

Discussion/Conclusion

We have proposed a method for single rare variant analysis with binary phenotypes by logistic regression penalized by log-Fpriors. Our method has the advantage of being easily extended to correct for confounding due to population structure and genetic relatedness through a data augmentation approach.
Epigenetic modulation in the pathogenesis and treatment of inherited aortic aneurysm conditions
Authors: Kang Benjamin E. , Bagirzadeh Rustam , Bedja Djahida , Doyle Jefferson J. , MacFarlane Elena G. , Dietz Harry C.
Published: February 2021

Shprintzen-Goldberg syndrome (SGS) is a rare systemic connective tissue disorder characterized by craniofacial, skeletal, neurodevelopmental, cutaneous, and cardiovascular manifestations, including aortic root aneurysm. It has significant phenotypic overlap with both Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). We previously reported that SGS is caused by heterozygous mutations in the Sloan-Kettering Institute proto-oncogene (SKI), which encodes a potent suppressor of transforming growth factor beta (TGFβ) target gene expression. Herein, we show that mouse lines harboring orthologous amino acid substitutions inSkirecapitulate multiple human SGS phenotypic manifestations, including skin collagen deposition, skeletal kyphosis, behavioral hypoactivity, and aortic root aneurysm. Furthermore, aortic root aneurysm in SGS mice is associated with both increased acetylation of histone H3 at lysine-27 (H3K27) and TGFβ target gene expression, all of which can be ameliorated by pharmacological CBP/P300 inhibition in vivo; similar findings were seen in cultured dermal fibroblast from SGS patients. Aortic root growth is also abrogated in a mouse model of MFS by selective CBP/P300 inhibition in association with blunted expression of TGFβ target genes. These data document excessive H3K27 acetylation and hence TGFβ target gene expression in the pathogenesis of inherited presentations of aortic root aneurysm and the therapeutic potential of pharmacological epigenetic modulation.
Hydrogels Containing Gradients in Vascular Density Reveal Dose-Dependent Role of Angiocrine Cues on Stem Cell Behavior
Authors: Ngo Mai T. , Barnhouse Victoria R. , Gilchrist Aidan E. , Hunter Christine J. , Hensold Joy N. , Harley Brendan A.C.
Published: February 2021

Biomaterials that replicate patterns of microenvironmental signals from the stem cell niche offer the potential to refine platforms to regulate stem cell behavior. While significant emphasis has been placed on understanding the effects of biophysical and biochemical cues on stem cell fate, vascular-derived or angiocrine cues offer an important alternative signaling axis for biomaterial-based stem cell platforms. Elucidating dose-dependent relationships between angiocrine cues and stem cell fate are largely intractable in animal models and two-dimensional cell culture. In this study, we leverage microfluidic mixing devices to generate three-dimensional hydrogels containing lateral gradients in vascular density alongside murine hematopoietic stem cells (HSCs). Regional differences in vascular density can be generated via embossed gradients in cell, matrix, or growth factor density. HSCs co-cultured alongside vascular gradients reveal spatial patterns of HSC phenotype in response to angiocrine signals. Notably, decreased Akt signaling in high vessel density regions led to increased expansion of lineage-positive hematopoietic cells. This approach offers a combinatorial tool to rapidly screen a continuum of microenvironments with varying vascular, biophysical, and biochemical cues to reveal the influence of local angiocrine signals on HSC fate.
CompMap: an allele-specific expression read-counter based on competitive mapping
Authors: Sánchez-Ramírez S. , Cutter A. D.
Published: February 2021

Changes to regulatory sequences account for important phenotypic differences between species and populations. In heterozygote individuals, regulatory polymorphism typically manifests as allele-specific expression (ASE) of transcripts. ASE data from inter-species and inter-population hybrids, in conjunction with expression data from the parents, can be used to infer regulatory changes incisandtransthroughout the genome. Improper data handling, however, can create problems of mapping bias and excessive loss of information, which are prone to arise unintentionally from the cumbersome pipelines with multiple dependencies that are common among current methods. Here, we introduce a new, selfcontained method implemented in Python that generates allele-specific expression counts from genotype-specific map alignments. Rather than assessing individual SNPs, our approach sorts and counts reads within a given homologous region by comparing individual read-mapping statistics from each parental alignment. Reads that are aligned ambiguously to both references are resolved proportionally to the allele-specific matching read counts or statistically using a binomial distribution. Using simulations, we showCompMaphas low error rates in assessing regulatory divergence.

Availability

The Python code with examples and installation instructions is available on the GitHub repositoryhttps://github.com/santiagosnchez/CompMap

Contact

santiago.snchez@gmail.com

Supplementary information
Tooth chipping patterns inParanthropusdo not support regular hard food mastication
Authors: Towle Ian , Irish Joel D. , Loch Carolina
Published: February 2021

The paranthropines, includingParanthropus boiseiandParanthropus robustus, have often been considered hard-food specialists. The large post-canine teeth, thick enamel, and robust craniofacial features are often suggested to have evolved to cope with habitual mastication of hard foods. Yet, direct evidence for Paranthropus feeding behaviour often challenges these morphological interpretations. The main exception being antemortem tooth chipping which is still regularly used as evidence of habitual mastication of hard foods in this genus. In this study, data were compiled from the literature for six hominin species (includingP. boiseiandP. robustus) and 17 extant primate species, to analyse Paranthropus chipping patterns in a broad comparative framework. Severity of fractures, position on the dentition, and overall prevalence were compared among species. The results indicate that both Paranthropus species had a lower prevalence of tooth fractures compared to other fossil hominin species (P. boisei: 4%;P. robustus: 11%;Homo naledi: 37%;Australopithecus africanus: 17%;Homo neanderthalensis: 45%; EpipalaeolithicHomo sapiens: 29%); instead, their frequencies are similar to apes that masticate hard items in a non-regular frequency, including chimpanzees, gibbons, and gorillas (4%, 7% and 9% respectively). The prevalence is several times lower than in extant primates known to habitually consume hard items, such as sakis, mandrills, and sooty mangabeys (ranging from 28% to 48%). Comparative chipping analysis suggests that both Paranthropus species were unlikely habitual hard object eaters, at least compared to living durophage analogues.
Pulsed broad-spectrum UV light effectively inactivates SARS-CoV-2 on multiple surfaces
Authors: Jureka Alexander S. , Williams Caroline G. , Basler Christopher F.
Published: February 2021

The ongoing SARS-CoV-2 pandemic has resulted in an increased need for technologies capable of efficiently disinfecting public spaces as well as personal protective equipment. UV light disinfection is a well-established method for inactivating respiratory viruses. Here, we have determined that broad-spectrum, pulsed UV light is effective at inactivating SARS-CoV-2 on multiple surfaces. For hard, non-porous surfaces we observed that SARS-CoV-2 was inactivated to undetectable levels on plastic and glass with a UV dose of 34.9 mJ/cm2and stainless steel with a dose of 52.5 mJ/cm2. We also observed that broad-spectrum, pulsed UV light is effective at reducing SARS-CoV-2 on N95 respirator material to undetectable levels with a dose of 103 mJ/cm2. We included UV dosimeter cards that provide a colorimetric readout of UV dose and demonstrated their utility as a means to confirm desired levels of exposure were reached. Together, the results present here demonstrate that broad-spectrum, pulsed UV light is an effective technology for the inactivation of SARS-CoV-2 on multiple surfaces.
VisVariant: A java program to visualise genetic variants in next-generation sequencing data
Authors: Lau King Wai , Kleeman Michelle , Reuter Caroline , Lorincz Attila
Published: February 2021

Extremely large datasets are impossible or very difficult for humans to comprehend by standard mental approaches. Intuitive visualization of genetic variants in genomic sequencing data could help in the review and confirmation process of variants called by automated variant calling programs. To help facilitate interpretation of genetic variant next-generation sequencing (NGS) data we developed VisVariant, a customizable visualization tool that creates a figure showing the overlapping sequence information of thousands of individual reads including the variant and flanking regions.

Availability and implementation

Detailed information on how to download, install and run VisVariant together with an example is available on our github website [https://github.com/hugging-biorxiv/visvariant].
Dynamic Representation of the Subjective Value of Information
Authors: Kobayashi Kenji , Lee Sangil , Filipowicz Alexandre L. S. , McGaughey Kara D. , Kable Joseph W. , Nassar Matthew R.
Published: February 2021

To improve future decisions, people should seek information based on the value of information (VOI), which depends on the current evidence and the reward structure of the upcoming decision. When additional evidence is supplied, people should updateVOIto adjust subsequent information seeking, but the neurocognitive mechanisms of this updating process remain unknown. We used a modified beads task to examine how theVOIis represented and updated in the human brain. We theoretically derived, and empirically verified, a normative prediction that theVOIdepends on decision evidence and is biased by reward asymmetry. Using fMRI, we found that the subjectiveVOIis represented in right dorsolateral prefrontal cortex (DLPFC). Critically, thisVOIrepresentation was updated when additional evidence was supplied, showing that DLPFC dynamically tracks the up-to-dateVOIover time. These results provide new insights into how humans adaptively seek information in the service of decision making.