bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to novelty induced by change in size and complexity of familiar objects in Lister-Hooded rats, a follow-up of 2019 study
Authors: Pisula Wojciech , Modlinska Klaudia , Chrzanowska Anna , Goncikowska Katarzyna
Published: May 2021

This study examines the relationship between the change in size and change in complexity of well-known/familiarized objects and exploratory activity regulation in rats. In our experiment, the rats were exposed to three types of environmental novelty in a well-familiarized chamber: (1) addition of new tunnels to the chamber, (2) increased size of a familiarized tunnel, and (3) increased complexity of the existing tunnels. The animals responded to the addition of new tunnels with a significant behavioural shift involving increased exploration of the newly installed tunnels. This effect was stable across all three test trials. The rats exposed to a change in size of the familiar object initially reacted with a behavioural shift towards the enlarged tunnel but then re-focused on the unchanged one. There was also a significant increase in the frequency of moving between the zones of the chamber. The experimental group exposed to an increased complexity of familiar objects responded with a pronounced behavioural shift towards the complex tunnel and then slightly intensified their exploration of the unchanged one. A decrease was also observed in the frequency of moving between the zones of the chamber in the first and second test trials. In the effect size analysis, no differences were found in any of the three groups, which suggests that all manipulations had similar impact. The data obtained in this study supports the view that in rats, curiosity is at least two-dimensional: activational and cognitive. The activational aspect of curiosity may be explained by novelty-related arousal processes, while the cognitive processes are activated at longer time intervals in response to more complex stimulation. The validation of this hypothesis requires further research involving manipulations with a recently standardized protocol for measuring free exploration.
Comparing physiological responses during cognitive tests in virtual environments vs. in identical real-world environments
Authors: Kalantari Saleh , Rounds James D. , Kan Julia , Tripathi Vidushi , Cruz-Garza Jesus G.
Published: May 2021

Immersive virtual environments (VEs) are increasingly used to evaluate human responses to design variables. VEs provide a tremendous capacity to isolate and readily adjust specific features of an architectural or product design. They also allow researchers to safely and effectively measure performance factors and physiological responses. However, the success of this form of design-testing depends on the generalizability of response measurements between VEs and real-world contexts. At the current time, there is very limited research evaluating the consistency of human response data across identical real and virtual environments. Rendering tools were used to precisely replicate a real-world classroom in virtual space. Participants were recruited and asked to complete a series of cognitive tests in the real classroom and in the virtual classroom. Physiological data were collected during these tests, including electroencephalography (EEG), electrocardiography (ECG), electrooculography (EOG), galvanic skin response (GSR), and head acceleration. Participants’ accuracy on the cognitive tests did not significantly differ between the real classroom and the identical VE. However, the participants answered the tests more rapidly in the VE. No significant differences were found in eye blink rate and heart rate between the real and VR settings. Head acceleration and GSR variance were lower in the VE setting. Overall, EEG frequency band-power was not significantly altered between the real-world classroom and the VE. Analysis of EEG event-related potentials likewise indicated strong similarity between the real-world classroom and the VE, with a single exception related to executive functioning in a color-mismatch task.
On local intrinsic dimensionality of deformation in complex materials
Authors: Zhou Shuo , Tordesillas Antoinette , Pouragha Mehdi , Bailey James , Bondell Howard
Published: May 2021

We propose a new metric calleds-LID based on the concept ofLocal Intrinsic Dimensionalityto identify and quantify hierarchies of kinematic patterns in heterogeneous media.s-LID measures how outlying a grain’s motion is relative to itssnearest neighbors in displacement state space. To demonstrate the merits ofs-LID over the conventional measure of strain, we apply it to data on individual grain motions in a set of deforming granular materials. Several new insights into the evolution of failure are uncovered.First,s-LID reveals a hierarchy of concurrent deformation bands that prevails throughout loading history. These structures vary not only in relative dominance but also spatial and kinematic scales.Second,in the nascent stages of the pre-failure regime,s-LID uncovers a set of system-spanning, criss-crossing bands: microbands for smallsand embryonic-shearbands at larges, with the former being dominant. At the opposite extreme, in the failure regime, fully formed shearbands at largesdominate over the microbands. The novel patterns uncovered froms-LID contradict the common belief of a causal sequence where a subset of microbands coalesce and/or grow to form shearbands. Instead,s-LID suggests that the deformation of the sample in the lead-up to failure is governed by a complex symbiosis among these different coexisting structures, which amplifies and promotes the progressive dominance of the embryonic-shearbands over microbands.Third,we probed this transition from the microband-dominated regime to the shearband-dominated regime by systematically suppressing grain rotations. We found particle rotation to be an essential enabler of the transition to the shearband-dominated regime. When grain rotations are completely suppressed, this transition is prevented: microbands and shearbands coexist in relative parity.
Strong variations in urban allergenicity riskscapes due to poor knowledge of tree pollen allergenic potential
Authors: Sousa-Silva Rita , Smargiassi Audrey , Kneeshaw Daniel , Dupras Jérôme , Zinszer Kate , Paquette Alain
Published: May 2021

Exposure to allergenic tree pollen is an increasing environmental health issue in urban areas. However, reliable, well-documented, peer-reviewed data on the allergenicity of pollen from common tree species in urban environments are lacking. Using the concept of ‘riskscape’, we present and discuss evidence on how different tree pollen allergenicity datasets shape the risk for pollen-allergy sufferers in five cities with different urban forests and population densities: Barcelona, Montreal, New York City, Paris, and Vancouver. We also evaluate how tree diversity can modify the allergenic risk of urban forests. We show that estimates of pollen exposure risk range from 1 to 74% for trees considered to be highly allergenic in the same city. This variation results from differences in the pollen allergenicity datasets, which become more pronounced when a city’s canopy is dominated by only a few species and genera. In an increasingly urbanized world, diverse urban forests offer a potentially safer strategy aimed at diluting sources of allergenic pollen until better allergenicity data is developed. Our findings highlight an urgent need for a science-based approach to guide public health and urban forest planning.
In vitro performance of free and encapsulated bromelain
Authors: Ataide Janaína Artem , Cefali Letícia Caramori , Figueiredo Mariana Cecchetto , Braga Lúcia Elaine de Oliveira , Ruiz Ana Lúcia Tasca Gois , Foglio Mary Ann , Oliveira-Nascimento Laura , Mazzola Priscila Gava
Published: May 2021

For centuries, bromelain has been used to treat a range of ailments, even though its mechanism of action is not fully understood. Its therapeutic benefits include enzymatic debridement of the necrotic tissues of ulcers and burn wounds, besides anti-inflammatory, anti-tumor, and antioxidant properties. However, the protease is unstable and susceptible to self-hydrolysis over time. To overcome the stability issues of bromelain, a previous study formulated chitosan-bromelain nanoparticles (C-B-NP). We evaluated the optimized nanoformulation for in vitro antioxidant, cell antiproliferative activities and cell migration/proliferation in the scratch assay, comparing it with free bromelain. The antioxidant activity of free bromelain was concentration and time-dependent; after encapsulation, the activity level dropped, probably due to the slow release of protein from the nanoparticles. In vitro antiproliferative activity was observed in six tumor cell lines for free protein after 48 h of treatment (glioma, breast, ovarian, prostate, colon adenocarcinoma and chronic myeloid leukemia), but not for keratinocyte cells, enabling its use as an active topical treatment. In turn, C-B-NP only inhibited one cell line (chronic myeloid leukemia) and required higher concentrations for inhibition. After 144 h treatment of glioma cells with C-B-NP, growth inhibition was equivalent to that promoted by the free protein. This last result confirmed the delayed-release kinetics of the optimized formulation and bromelain integrity. Finally, a scratch assay with keratinocyte cells showed that C-B-NP achieved more than 90% wound retraction after 24 h, compared to no retraction with the free bromelain. Therefore, nanoencapsulation of bromelain with chitosan conferred physical protection, delayed release, and wound retraction activity to the formulation, properties that favor topical formulations with a modified release. In addition, the promising results with the glioma cell line point to further studies of C-B-NP for anti-tumor treatments.
Biochemical and structural insights into Rab12 interactions with RILP and its family members
Authors: Omar Jana , Rosenbaum Efrat , Efergan Adi , Sneineh Bayan Abu , Yeheskel Adva , Maruta Yuto , Fukuda Mitsunori , Sagi-Eisenberg Ronit
Published: May 2021

Alongside its biosynthetic functions, the small GTPase Rab12 negatively regulates mast cell (MC) exocytosis by its interaction with RILP to promote retrograde transport of the MC secretory granules. Given the role of Rab effectors in mediating Rab functions, in this study we used biochemical and in silico tools to decipher Rab12 interactions with its RILP family effectors. We show that Rab12 interacts with RILP, RILP-L1 and RILP-L2 independently of each other, whereby lysine-71, in mouse Rab12, is critical for Rab12 interactions with RILP-L1 or RILP-L2, but is dispensable for the binding of RILP. Focusing on RILP, and relying on molecular dynamics simulations, functional mutational analyses and peptide inhibition assays, we propose a model for the Rab12-RILP complex, consisting of a RILP homodimer and a single molecule of active Rab12, that interacts with the RILP homology domain (RHD) of one RILP monomer and a C-terminal threonine in the other monomer via its switch I and switch II regions. Mutational analyses of RILP RHD also demonstrate its involvement in the regulation of MC secretory granule transport. Jointly, our results provide structural and functional insights into the Rab12-RILP complex on the basis of which new tools could be generated for decoding Rab12 functions.
Caesarean delivery is associated with increased blood pressure in young adult offspring
Authors: Rerkasem Amaraporn , Maessen Sarah E. , Wongthanee Antika , Pruenglampoo Sakda , Mangklabruks Ampica , Sripan Patumrat , Derraik José G. B. , Rerkasem Kittipan
Published: May 2021

We examined the associations between caesarean section (CS) delivery and cardiovascular risk factors in young adults in Thailand. Participants were 632 offspring from a birth cohort in Chiang Mai (Northern Thailand), born in 1989–1990 and assessed in 2010 at a mean age of 20.6 years, including 57 individuals (9.0%) born by CS and 575 born vaginally. Clinical assessments included anthropometry, blood pressure (BP), carotid intima-media thickness, and fasting blood glucose, insulin, and lipid profile. Young adults born by CS had systolic BP (SBP) 6.2 mmHg higher (p < 0.001), diastolic BP 3.2 mmHg higher (p = 0.029), and mean arterial pressure (MAP) 4.1 mmHg higher (p = 0.003) than those born vaginally. After covariate adjustments, SBP and MAP remained 4.1 mmHg (p = 0.006) and 2.9 mmHg (p = 0.021) higher, respectively, in the CS group. The prevalence of abnormal SBP (i.e., pre-hypertension or hypertension) in the CS group was 2.5 times that of those born vaginally (25.0% vs 10.3%; p = 0.003), with an adjusted relative risk of abnormal SBP 1.9 times higher (95% CI 1.15, 2.98; p = 0.011). There were no differences in anthropometry (including obesity risk) or other metabolic parameters. In this birth cohort in Thailand, CS delivery was associated with increased blood pressure in young adulthood.
Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1
Authors: Choudhury Arunabh , Mohammad Taj , Samarth Nikhil , Hussain Afzal , Rehman Md. Tabish , Islam Asimul , Alajmi Mohamed F. , Singh Shailza , Hassan Md. Imtaiyaz
Published: May 2021

Conserved telomere maintenance component 1 (CTC1) is an important component of the CST (CTC1-STN1-TEN1) complex, involved in maintaining the stability of telomeric DNA. Several non-synonymous single-nucleotide polymorphisms (nsSNPs) in CTC1 have been reported to cause Coats plus syndrome and Dyskeratosis congenital diseases. Here, we have performed sequence and structure analyses of nsSNPs of CTC1 using state-of-the-art computational methods. The structure-based study focuses on the C-terminal OB-fold region of CTC1. There are 11 pathogenic mutations identified, and detailed structural analyses were performed. These mutations cause a significant disruption of noncovalent interactions, which may be a possible reason for CTC1 instability and consequent diseases. To see the impact of such mutations on the protein conformation, all-atom molecular dynamics (MD) simulations of CTC1-wild-type (WT) and two of the selected mutations, R806C and R806L for 200 ns, were carried out. A significant conformational change in the structure of the R806C mutant was observed. This study provides a valuable direction to understand the molecular basis of CTC1 dysfunction in disease progression, including Coats plus syndrome.
An SIR-type epidemiological model that integrates social distancing as a dynamic law based on point prevalence and socio-behavioral factors
Authors: Cabrera Maritza , Córdova-Lepe Fernando , Gutiérrez-Jara Juan Pablo , Vogt-Geisse Katia
Published: May 2021

Modeling human behavior within mathematical models of infectious diseases is a key component to understand and control disease spread. We present a mathematical compartmental model of Susceptible–Infectious–Removed to compare the infected curves given by four different functional forms describing the transmission rate. These depend on the distance that individuals keep on average to others in their daily lives. We assume that this distance varies according to the balance between two opposite thrives: the self-protecting reaction of individuals upon the presence of disease to increase social distancing and their necessity to return to a culturally dependent natural social distance that occurs in the absence of disease. We present simulations to compare results for different society types on point prevalence, the peak size of a first epidemic outbreak and the time of occurrence of that peak, for four different transmission rate functional forms and parameters of interest related to distancing behavior, such as: the reaction velocity of a society to change social distance during an epidemic. We observe the vulnerability to disease spread of close contact societies, and also show that certain social distancing behavior may provoke a small peak of a first epidemic outbreak, but at the expense of it occurring early after the epidemic onset, observing differences in this regard between society types. We also discuss the appearance of temporal oscillations of the four different transmission rates, their differences, and how this oscillatory behavior is impacted through social distancing; breaking the unimodality of the actives-curve produced by the classical SIR-model.
Cues to gender and racial identity reduce creativity in diverse social networks
Authors: Baten Raiyan Abdul , Aslin Richard N. , Ghoshal Gourab , Hoque Ehsan
Published: May 2021

The characteristics of social partners have long been hypothesized as influential in guiding group interactions. Understanding how demographic cues impact networks of creative collaborators is critical for elevating creative performances therein. We conducted a randomized experiment to investigate how the knowledge of peers’ gender and racial identities distorts people’s connection patterns and the resulting creative outcomes in a dynamic social network. Consistent with prior work, we found that creative inspiration links are primarily formed with top idea-generators. However, when gender and racial identities are known, not only is there (1) an increase of $$82.03\%$$

82.03
%

in the odds of same-gender connections to persist (but not for same-race connections), but (2) the semantic similarity of idea-sets stimulated by these connections also increase significantly compared to demography-agnostic networks, negatively impacting the outcomes of divergent creativity. We found that ideas tend to be significantly more homogeneous within demographic groups than between, taking away diversity-bonuses from similarity-based links and partly explaining the results. These insights can inform intelligent interventions to enhance network-wide creative performances.
Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies
Authors: Rawat Puneet , Sharma Divya , Srivastava Ambuj , Janakiraman Vani , Gromiha M. Michael
Published: May 2021

The urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications.
A generative adversarial network-based abnormality detection using only normal images for model training with application to digital breast tomosynthesis
Authors: Swiecicki Albert , Konz Nicholas , Buda Mateusz , Mazurowski Maciej A.
Published: May 2021

Deep learning has shown tremendous potential in the task of object detection in images. However, a common challenge with this task is when only a limited number of images containing the object of interest are available. This is a particular issue in cancer screening, such as digital breast tomosynthesis (DBT), where less than 1% of cases contain cancer. In this study, we propose a method to train an inpainting generative adversarial network to be used for cancer detection using only images that do not contain cancer. During inference, we removed a part of the image and used the network to complete the removed part. A significant error in completing an image part was considered an indication that such location is unexpected and thus abnormal. A large dataset of DBT images used in this study was collected at Duke University. It consisted of 19,230 reconstructed volumes from 4348 patients. Cancerous masses and architectural distortions were marked with bounding boxes by radiologists. Our experiments showed that the locations containing cancer were associated with a notably higher completion error than the non-cancer locations (mean error ratio of 2.77). All data used in this study has been made publicly available by the authors.
Drug repurposing for ligand-induced rearrangement of Sirt2 active site-based inhibitors via molecular modeling and quantum mechanics calculations
Authors: Bharadwaj Shiv , Dubey Amit , Kamboj Nitin Kumar , Sahoo Amaresh Kumar , Kang Sang Gu , Yadava Umesh
Published: May 2021

Sirtuin 2 (Sirt2) nicotinamide adenine dinucleotide-dependent deacetylase enzyme has been reported to alter diverse biological functions in the cells and onset of diseases, including cancer, aging, and neurodegenerative diseases, which implicate the regulation of Sirt2 function as a potential drug target. Available Sirt2 inhibitors or modulators exhibit insufficient specificity and potency, and even partially contradictory Sirt2 effects were described for the available inhibitors. Herein, we applied computational screening and evaluation of FDA-approved drugs for highly selective modulation of Sirt2 activity via a unique inhibitory mechanism as reported earlier for SirReal2 inhibitor. Application of stringent molecular docking results in the identification of 48 FDA-approved drugs as selective putative inhibitors of Sirt2, but only top 10 drugs with docking scores > − 11 kcal/mol were considered in reference to SirReal2 inhibitor for computational analysis. The molecular dynamics simulations and post-simulation analysis of Sirt2-drug complexes revealed substantial stability for Fluphenazine and Nintedanib with Sirt2. Additionally, developed 3D-QSAR-models also support the inhibitory potential of drugs, which exclusively revealed highest activities for Nintedanib (pIC50 ≥ 5.90 µM). Conclusively, screened FDA-approved drugs were advocated as promising agents for Sirt2 inhibition and required in vitro investigation for Sirt2 targeted drug development.
Validation of reference genes for use in untreated bovine fibroblasts
Authors: Toorani T. , Mackie P. M. , Mastromonaco G. F.
Published: May 2021

Proper normalization of RT-qPCR data is pivotal to the interpretation of results and accuracy of scientific conclusions. Though different approaches may be taken, normalization against multiple reference genes is now standard practice. Genes traditionally used and deemed constitutively expressed have demonstrated variability in expression under different experimental conditions, necessitating the proper validation of reference genes prior to utilization. Considering the wide use of fibroblasts in research and scientific applications, it is imperative that suitable reference genes for fibroblasts of different animal origins and conditions be elucidated. Previous studies on bovine fibroblasts have tested limited genes and/or samples. Herein, we present an extensive study investigating the expression stability of 16 candidate reference genes across 7 untreated bovine fibroblast cell lines subjected to controlled conditions. Data were analysed using various statistical tools and algorithms, including geNorm, NormFinder, BestKeeper, and RefFinder. A combined use ofGUSBandRPL13Awas determined to be the best approach for data normalization in untreated bovine fibroblasts.
Refinery wastewater treatment via a multistage enhanced biochemical process
Authors: Wang Chunhua , Chen Zijian , Li Yuanhua , Feng Kejun , Peng Zhongli , Zhu Yongjuan , Yang Xiaofang
Published: May 2021

Petroleum refinery wastewater (PRWW) that contains recalcitrant components as the major portion of constituents is difficult to treat by conventional biological processes. An effective and economical biological treatment process was established to treat industrial PRWW with an influent COD of over 2500 mg L−1 in this research. This process is mainly composed of internal circulation biological aerated filter (ICBAF), hydrolysis acidfication (HA), two anaerobic–aerobic (A/O) units, a membrane biological reactor (MBR), and ozone-activated carbon (O3-AC) units. The results showed that, overall, this system removed over 94% of the COD, BOD5, ammonia nitrogen (NH4+-N) and phosphorus in the influent, with the ICBAF unit accounting for 54.6% of COD removal and 83.6% of BOD5 removal, and the two A/O units accounting for 33.3% of COD removal and 9.4% of BOD5 removal. The degradation processes of eight organic pollutants and their removal via treatment were also analyzed. Furthermore, 26 bacteria were identified in this system, with Proteobacteria and Acidobacteria being the most dominant. Ultimately, the treatment process exhibited good performance in degrading complex organic pollutants in the PRWW.
Off-training physical activity and training responses as determinants of sleep quality in young soccer players
Authors: Mateus Nuno , Exel Juliana , Gonçalves Bruno , Weldon Anthony , Sampaio Jaime
Published: May 2021

This study aimed to quantify and assess the relationship of young soccer players' off-training physical activity (PA) and training responses on sleep quality. Eleven adolescent soccer players (13 ± 0.5 years old) were monitored during weekdays for four consecutive weeks, throughout soccer practice days. Off-training PA and sleep quality were assessed using 100 Hz tri-axial accelerometers and training responses analyzed using 20 Hz global positioning measurement units. A cluster analysis classified all cases into three different dimensions, (1) off-training PA, (2) training responses and (3) sleep quality. For each dimension, the most important variables for classifying the cases into clusters were sedentary PA and moderate-to-vigorous PA; total distance covered and impacts; and sleep onset latency and sleep fragmentation index, respectively. Afterwards, a correspondence analysis was used to identify whether off-training PA and training responses affected sleep quality. Results exposed that high to medium off-training PA combined with medium to high training responses may have decreased sleep quality. Conversely, no correspondence was observed between off-training PA and training responses, with higher sleep quality. This study emphasizes the importance of sports organizations adopting a holistic approach to youth soccer players’ development, that appropriately considers the inter-relationship between lifestyle, performance and health-related information.
Ratio of venous-to-arterial PCO2 to arteriovenous oxygen content difference during regional ischemic or hypoxic hypoxia
Authors: Mallat Jihad , Vallet Benoit
Published: May 2021

The purpose of the study was to evaluate the behavior of the venous-to-arterial CO2 tension difference (ΔPCO2) over the arterial-to-venous oxygen content difference (ΔO2) ratio (ΔPCO2/ΔO2) and the difference between venous-to-arterial CO2 content calculated with the Douglas’ equation (ΔCCO2D) over ΔO2 ratio (ΔCCO2D/ΔO2) and their abilities to reflect the occurrence of anaerobic metabolism in two experimental models of tissue hypoxia: ischemic hypoxia (IH) and hypoxic hypoxia (HH). We also aimed to assess the influence of metabolic acidosis and Haldane effects on the PCO2/CO2 content relationship. In a vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system, the oxygen delivery (DO2) was lowered in a stepwise manner to decrease it beyond critical DO2 (DO2crit) by lowering either arterial PO2 (HH-model) or flow (IH-model). Twelve anesthetized and mechanically ventilated dogs were studied, 6 in each model. Limb DO2, oxygen consumption ($${\dot{\text{V}}\text{O}}_{2}$$

V
˙

O

2

), ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 were obtained every 15 min. Beyond DO2crit, $${\dot{\text{V}}\text{O}}_{2}$$

V
˙

O

2

decreased, indicating dysoxia. ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 increased significantly only after reaching DO2crit in both models. At DO2crit, ΔPCO2/ΔO2 was significantly higher in the HH-model than in the IH-model (1.82 ± 0.09 vs. 1.39 ± 0.06, p = 0.002). At DO2crit, ΔCCO2D/ΔO2 was not significantly different between the two groups (0.87 ± 0.05 for IH vs. 1.01 ± 0.06 for HH, p = 0.09). Below DO2crit, we observed a discrepancy between the behavior of the two indices. In both models, ΔPCO2/ΔO2 continued to increase significantly (higher in the HH-model), whereas ΔCCO2D/ΔO2 tended to decrease to become not significantly different from its baseline in the IH-model. Metabolic acidosis significantly influenced the PCO2/CO2 content relationship, but not the Haldane effect. ΔPCO2/ΔO2 was able to depict the occurrence of anaerobic metabolism in both tissue hypoxia models. However, at very low DO2 values, ΔPCO2/ΔO2 did not only reflect the ongoing anaerobic metabolism; it was confounded by the effects of metabolic acidosis on the CO2–hemoglobin dissociation curve, and then it should be interpreted with caution.
Detection of Plasmodium falciparum in laboratory-reared and naturally infected wild mosquitoes using near-infrared spectroscopy
Authors: Da Dari F. , McCabe Ruth , Somé Bernard M. , Esperança Pedro M. , Sala Katarzyna A. , Blight Josua , Blagborough Andrew M. , Dowell Floyd , Yerbanga Serge R. , Lefèvre Thierry , Mouline Karine , Dabiré Roch K. , Churcher Thomas S.
Published: May 2021

There is an urgent need for high throughput, affordable methods of detecting pathogens inside insect vectors to facilitate surveillance. Near-infrared spectroscopy (NIRS) has shown promise to detect arbovirus and malaria in the laboratory but has not been evaluated in field conditions. Here we investigate the ability of NIRS to identify Plasmodium falciparum in Anopheles coluzzii mosquitoes. NIRS models trained on laboratory-reared mosquitoes infected with wild malaria parasites can detect the parasite in comparable mosquitoes with moderate accuracy though fails to detect oocysts or sporozoites in naturally infected field caught mosquitoes. Models trained on field mosquitoes were unable to predict the infection status of other field mosquitoes. Restricting analyses to mosquitoes of uninfectious and highly-infectious status did improve predictions suggesting sensitivity and specificity may be better in mosquitoes with higher numbers of parasites. Detection of infection appears restricted to homogenous groups of mosquitoes diminishing NIRS utility for detecting malaria within mosquitoes.
LSD1-mediated demethylation of OCT4 safeguards pluripotent stem cells by maintaining the transcription of PORE-motif-containing genes
Authors: Dan Songsong , Song Yuelin , Duan Xiaotao , Pan Xiao , Chen Cheng , She Shiqi , Su Tong , Li Jingchao , Chen Xinyu , Zhou Yanwen , Chen Wenjie , Zhang Xiaobing , Pan Xiaoyun , Wang Ying-Jie , Kang Bo
Published: May 2021

Reversible lysine methylation is essential for regulating histones and emerges to critically regulate non-histone proteins as well. Here we show that the master transcription factor OCT4 in pluripotent stem cells (PSCs) was methylated at multiple lysine residues. LSD1 that is highly expressed in PSCs can directly interact with and demethylate OCT4 at lysine 222 (K222) in the flexible linker region. Reduced LSD1 activity led to the methylation of OCT4-K222 that diminished the differentiation potential of PSCs while facilitating proteasome-independent degradation of OCT4 proteins. Furthermore, site-specifically replacing K222 with phenylalanine to mimic the constitutively methylated lysine promoted the ‘locked-in’ mode engagement of the OCT4 PORE-homodimers that tightly bind to and block the transcription of multiple PORE-motif-containing target genes regulating cell fate determination and cell junction organization, and thereby reducing the pluripotency of PSCs. Thus, LSD1-mediated demethylation of OCT4 plays a crucial role in restricting the ‘locked-in’ mode binding of OCT4 PORE-homodimers to the PORE-motif-containing genes and thereby maintaining their transcription to safeguard the pluripotency of PSCs.
Divergent nucleic acid allocation in juvenile insects of different metamorphosis modes
Authors: Villar-Argaiz Manuel , López-Rodríguez Manuel J. , Tierno de Figueroa J. Manuel
Published: May 2021

Nucleic acids help clarify variation in species richness of insects having different metamorphosis modes, a biological conundrum. Here we analyse nucleic acid contents of 639 specimens of aquatic insects collected from four high mountain streams of Sierra Nevada in southern Spain to test whether the allocation to RNA or DNA content differs during ontogeny between juvenile insects undergoing direct (hemimetabolous) or indirect (holometabolous) metamorphosis. The results show that RNA content as a function of body mass was negatively correlated to insect body length in four out of six and three out of six of the holometabolan and hemimetabolan taxa, respectively. Although no significant differences in RNA content were found between holometabolans and hemimetabolans, the significant interaction between body length and metamorphosis mode for RNA and RNA:DNA indicates a strong ontogenetic component to RNA allocation. In addition, our finding of lower DNA content in holometabolans relative to hemimetabolans agree with the analysis of empirical genome data in aquatic and terrestrial insects, and extend to this class of arthropods the “growth rate-genome size-nutrient limitation” hypothesis that differences in allocation between RNA and DNA may reflect fundamental evolutionary trade-off of life-history strategies associated with high growth rates (and RNA content) in holometabolans at the expense of diminished genome sizes.
Predicting sex from retinal fundus photographs using automated deep learning
Authors: Korot Edward , Pontikos Nikolas , Liu Xiaoxuan , Wagner Siegfried K. , Faes Livia , Huemer Josef , Balaskas Konstantinos , Denniston Alastair K. , Khawaja Anthony , Keane Pearse A.
Published: May 2021

Deep learning may transform health care, but model development has largely been dependent on availability of advanced technical expertise. Herein we present the development of a deep learning model by clinicians without coding, which predicts reported sex from retinal fundus photographs. A model was trained on 84,743 retinal fundus photos from the UK Biobank dataset. External validation was performed on 252 fundus photos from a tertiary ophthalmic referral center. For internal validation, the area under the receiver operating characteristic curve (AUROC) of the code free deep learning (CFDL) model was 0.93. Sensitivity, specificity, positive predictive value (PPV) and accuracy (ACC) were 88.8%, 83.6%, 87.3% and 86.5%, and for external validation were 83.9%, 72.2%, 78.2% and 78.6% respectively. Clinicians are currently unaware of distinct retinal feature variations between males and females, highlighting the importance of model explainability for this task. The model performed significantly worse when foveal pathology was present in the external validation dataset, ACC: 69.4%, compared to 85.4% in healthy eyes, suggesting the fovea is a salient region for model performance OR (95% CI): 0.36 (0.19, 0.70) p = 0.0022. Automated machine learning (AutoML) may enable clinician-driven automated discovery of novel insights and disease biomarkers.
Novel computational analysis of large transcriptome datasets identifies sets of genes distinguishing chronic obstructive pulmonary disease from healthy lung samples
Authors: Roessler Fabienne K. , Benedikter Birke J. , Schmeck Bernd , Bar Nadav
Published: May 2021

Chronic obstructive pulmonary disease (COPD) kills over three million people worldwide every year. Despite its high global impact, the knowledge about the underlying molecular mechanisms is still limited. In this study, we aimed to extend the available knowledge by identifying a small set of COPD-associated genes. We analysed different publicly available gene expression datasets containing whole lung tissue (WLT) and airway epithelium (AE) samples from over 400 human subjects for differentially expressed genes (DEGs). We reduced the resulting sets of 436 and 663 DEGs using a novel computational approach that utilises a random depth-first search to identify genes which improve the distinction between COPD patients and controls along the first principle component of the data. Our method identified small sets of 10 and 15 genes in the WLT and AE, respectively. These sets of genes significantly (p < 10–20) distinguish COPD patients from controls with high fidelity. The final sets revealed novel genes like cysteine rich protein 1 (CRIP1) or secretoglobin family 3A member 2 (SCGB3A2) that may underlie fundamental molecular mechanisms of COPD in these tissues.
Comparison of different techniques for the management of venous steno-occlusive lesions during placement of peripherally inserted central catheter
Authors: Yang Woo Jin , Kang Danbee , Shin Ji Hoon , Jang Eun Ho , Noh Seung Yeon , Park Suyoung , Chu Hee Ho , Kim Jong Woo
Published: May 2021

The purpose of this study is to investigate strategies for peripherally inserted central catheter (PICC) placement in patients with venous steno-occlusive lesion (VSOL). We performed a retrospective cohort study in adults with central or peripheral VSOL who underwent PICC placement procedures from January 2015 to December 2018. Four different strategies [selecting alternative pathway/over the wire (SAP/OTW), percutaneous transluminal angioplasty (PTA), re-puncture in ipsilateral arm (RIA), and catheter placement in the contralateral arm (CICA)] were analyzed and we compared the clinical outcomes by strategy and compared the strategy between central and peripheral VSOLs. During 4 years, 258 PICC procedures performed in patients with VSOLs, 100 PICC were included in the analysis. The overall technical success rate of initial attempt with SAP/OTW was 32.2%. As a second-line technique, PTA was most frequently used in both central (100%) and peripheral (68.2%) VSOL groups. The clinical success rates within 2 months of SAP/OTW, PTA, RIA, CICA were 55.2%, 43.2%, 14.3%, and 33.3%, respectively (P = 0.24). In conclusion, when the SAP/OTW failed, the PTA can be preferred as a second-line technique for both central and peripheral VSOLs. When guidewire passage fails, the operator could adopt the RIA or CICA technique as an alternative method.
Detection and quantification of bovine papillomavirus DNA by digital droplet PCR in sheep blood
Authors: Roperto Sante , Cutarelli Anna , Corrado Federica , De Falco Francesca , Buonavoglia Canio
Published: May 2021

Highly pathogenic bovine papillomaviruses (BPVs) were detected and quantified for the first time using digital droplet polymerase chain reaction (ddPCR) by liquid biopsy in 103 clinically healthy sheep. Overall, ddPCR detected BPVs in 68 blood samples (66%). BPV infection by a single genotype was revealed in 61.8% of the blood samples, and BPV coinfection by double, triple or quadruple genotypes was observed in 38.2% of liquid biopsies. The BPV-2 genotype was most frequently seen in sheep, whereas BPV-1 was the least common. Furthermore, ddPCR was very useful for detection and quantification; the BPV-14 genotype was observed for the first time in ovine species, displaying the highest prevalence in some geographical areas (Apulia). In 42 of the positive samples (61.8%), a single BPV infection was observed, 26 of which were caused by BPV-2 (61.9%) and 7 by BPV-13 (16.7%). BPV-14 was responsible for 7 single infections (16.7%) and BPV-1 for 2 single infections (4.7%). Multiple BPV coinfections were observed in the remaining 26 positive samples (38.2%), with dual BPV-2/BPV-13 infection being the most prevalent (84.6%). BPV infection by triple and quadruple genotypes was also observed in 11.5% and 3.8% of cases, respectively. The present study showed that ddPCR, a biotechnological refinement of conventional PCR, is by far the most sensitive and accurate assay for BPV detection compared to conventional qPCR. Therefore, ddPCR displayed an essential diagnostic and epidemiological value very useful for the identification of otherwise undetectable BPV genotypes as well as their geographical distributions and suggesting that animal husbandry practices contribute to cross-species transmission of BPVs.
Quantitative trait locus mapping identifies the Gpnmb gene as a modifier of mouse macrophage lysosome function
Authors: Robinet Peggy , Ritchey Brian , Lorkowski Shuhui Wang , Alzayed Alexander M. , DeGeorgia Sophia , Schodowski Eve , Traughber C. Alicia , Smith Jonathan D.
Published: May 2021

We have previously shown that the DBA/2J versus AKR/J mouse strain is associated with decreased autophagy-mediated lysosomal hydrolysis of cholesterol esters. Our objective was to determine differences in lysosome function in AKR/J and DBA/2J macrophages, and identify the responsible genes. Using a novel dual-labeled indicator of lysosome function, DBA/2J versus AKR/J bone marrow derived macrophages had significantly decreased lysosome function. We performed quantitative trait loci mapping of lysosome function in bone marrow macrophages from an AKR/J × DBA/2J strain intercross. Four distinct lysosome function loci were identified, which we named macrophage lysosome function modifier (Mlfm) Mlfm1 through Mlfm4. The strongest locus Mlfm1 harbors the Gpnmb gene, which has been shown to recruit autophagy protein light chain 3 to autophagosomes for lysosome fusion. The parental DBA/2J strain has a nonsense variant in Gpnmb. siRNA knockdown of Gpnmb in AKR/J macrophages decreased lysosome function, and Gpnmb deletion through CRISP/Cas9 editing in RAW 264.7 mouse macrophages also demonstrated a similar result. Furthermore, a DBA/2 substrain, called DBA/2J-Gpnmb+/SjJ, contains the wildtype Gpnmb gene, and macrophages from this Gpnmb-preserved DBA/2 substrain exhibited recovered lysosome function. In conclusion, we identified Gpnmb as a causal modifier gene of lysosome function in this strain pair.
Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
Authors: Bando Silvia Yumi , Bertonha Fernanda Bernardi , Pimentel-Silva Luciana Ramalho , de Oliveira João Gabriel Mansano , Carneiro Marco Antonio Duarte , Oku Mariana Hiromi Manoel , Wen Hung-Tzu , Castro Luiz Henrique Martins , Moreira-Filho Carlos Alberto
Published: May 2021

In about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules’ main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.
An intact complement system dampens cornea inflammation during acute primary HSV-1 infection
Authors: Filiberti Adrian , Gmyrek Grzegorz B. , Berube Amanda N. , Royer Derek J. , Carr Daniel J. J.
Published: May 2021

Corneal transparency is an essential characteristic necessary for normal vision. In response to microbial infection, the integrity of the cornea can become compromised as a result of the inflammatory response and the ensuing tissue pathology including neovascularization (NV) and collagen lamellae destruction. We have previously found complement activation contributes to cornea pathology-specifically, denervation in response to HSV-1 infection. Therefore, we investigated whether the complement system also played a role in HSV-1-mediated neovascularization. Using wild type (WT) and complement component 3 deficient (C3 KO) mice infected with HSV-1, we found corneal NV was accelerated associated with an increase in inflammatory monocytes (CD11b+CCR2+CD115+/−Ly6G−Ly6Chigh), macrophages (CD11b+CCR2+CD115+Ly6G−Ly6Chigh) and a subpopulation of granulocytes/neutrophils (CD11b+CCR2−CD115+Ly6G+Ly6Clow). There were also increases in select pro-inflammatory and pro-angiogenic factors including IL-1α, matrix metalloproteinases (MMP)-2, MMP-3, MMP-8, CXCL1, CCL2, and VEGF-A that coincided with increased inflammation, neovascularization, and corneal opacity in the C3 KO mice. The difference in inflammation between WT and C3 KO mice was not driven by changes in virus titer. However, viral antigen clearance was hindered in C3 KO mouse corneas suggesting the complement system has a dynamic regulatory role within the cornea once an inflammatory cascade is initiated by HSV-1.
Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit α2δ-1 but not α2δ-3
Authors: Meyer James O. , Dolphin Annette C.
Published: May 2021

N-type voltage-gated calcium channels (CaV2.2) are predominantly expressed at presynaptic terminals, and their function is regulated by auxiliary α2δ and β subunits. All four mammalian α2δ subunits enhance calcium currents through CaV1 and CaV2 channels, and this increase is attributed, in part, to increased CaV expression at the plasma membrane. In the present study we provide evidence that α2δ-1, like α2δ-2, is recycled to the plasma membrane through a Rab11a-dependent endosomal recycling pathway. Using a dominant-negative Rab11a mutant, Rab11a(S25N), we show that α2δ-1 increases plasma membrane CaV2.2 expression by increasing the rate and extent of net forward CaV2.2 trafficking in a Rab11a-dependent manner. Dominant-negative Rab11a also reduces the ability of α2δ-1 to increase CaV2.2 expression on the cell-surface of hippocampal neurites. In contrast, α2δ-3 does not enhance rapid forward CaV2.2 trafficking, regardless of whether Rab11a(S25N) is present. In addition, whole-cell CaV2.2 currents are reduced by co-expression of Rab11a(S25N) in the presence of α2δ-1, but not α2δ-3. Taken together these data suggest that α2δ subtypes participate in distinct trafficking pathways which in turn influence the localisation and function of CaV2.2.
Quantum entanglement and statistics of photons on a beam splitter in the form of coupled waveguides
Authors: Makarov D. N. , Gusarevich E. S. , Goshev A. A. , Makarova K. A. , Kapustin S. N. , Kharlamova A. A. , Tsykareva Yu. V.
Published: May 2021

It is well known that a beam splitter (BS) can be used as a source of photon quantum entanglement. This is due to the fact that the statistics of photons changes at the output ports of the BS. Usually, quantum entanglement and photon statistics take into account the constancy of the reflection coefficient R or the transmission coefficient T of the BS, where $$R + T = 1$$

R
+
T
=
1

. It has recently been shown that if BS is used in the form of coupled waveguides, the coefficients R and T will depend on the photon frequencies. In this paper, it is shown that the quantum entanglement and statistics of photons at the output ports of a BS can change significantly if a BS is used in the form of coupled waveguides, where the coefficients R and T are frequency-dependent.