bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing the charge carrier kinetics in perovskite solar cells affected by mesoscopic structures and defect states from simple transient photovoltage measurements
Authors: Hidayat Rahmat , Nurunnizar Adhita Asma , Fariz Alvin , Herman  , Rosa Erlyta Septa , Shobih  , Oizumi Tomohisa , Fujii Akihiko , Ozaki Masanori
Published: November 2020

This report shows that, by using simple transient photovoltage (TPV) measurements, we can reveal a significant correlation between the TPV decay characteristics and the performance of these perovskite solar cells. TPV decay seems to be composed of a rising part in a short interval after photoexcitation and a long decaying part that extends up to tens of milliseconds. These decay behaviors look different depending on the mesoscopic structures and the perovskite morphology formed therein, as seen from their Scanning Electron Microcopy images and X-ray diffraction patterns. The decay part can be fitted with a three-exponential decay, which reflects different kinetics of electrons in the perovskite/TiO2 layer. On the other hand, the rising part must be fit by a decay equation derived by employing the convolution theorem, where the rising part can be assigned to the electron transport process inside the perovskite layer and the decaying part can be assigned to electron back-transfer. The characteristics can be then understood by considering the effect of crystal defects and trap states in the perovskite grains and perovskite interface with its transport layer, which is TiO2 in this study. Although the TPV decay occurs in a time range much longer than the primary process of photoexcitation as commonly observed in transient photoluminescence spectroscopy, the processes involved in this TPV strongly correlates with the performance of these perovskite solar cells.
Transcriptomic and life history responses of the mayfly Neocloeon triangulifer to chronic diel thermal challenge
Authors: Chou Hsuan , Jima Dereje D. , Funk David H. , Jackson John K. , Sweeney Bernard W. , Buchwalter David B.
Published: November 2020

To better understand the effects of transient thermal stress in an aquatic insect, we first identified static temperatures associated with fitness deficits, and then reared larvae from egg hatch to adulthood under diurnally variable regimens including daily forays into deleterious temperatures. We sampled mature larvae at the coolest and warmest portions of their respective regimens for RNA-seq analysis. Few transcripts (28) were differentially expressed when larvae oscillated between favorable temperatures, while 614 transcripts were differentially expressed when experiencing daily transient thermal stress. Transcripts associated withN-glycan processing were downregulated while those associated with lipid catabolism and chitin turnover were significantly upregulated in heat stressed larvae. An across-regimen comparison of differentially expressed transcripts among organisms sampled at comparable temperatures demonstrated that the effects of daily thermal stress persisted even when larvae were sampled at a more optimal temperature (806 differentially expressed transcripts). The chronically stressed population had reduced expression of transcripts related to ATP synthesis, mitochondrial electron chain functions, gluconeogenesis and glycolytic processes while transcripts associated with cell adhesion, synaptic vesicle transport, regulation of membrane potential and lipid biosynthesis increased. Comparisons of constant vs. variable temperatures revealed that the negative consequences of time spent at stressful temperatures were not offset by more time spent at optimal temperatures.
Repeatability of the 6-min walk test in non-cystic fibrosis bronchiectasis
Authors: Rovedder Paula Maria Eidt , Fernandes Rafael Oliveira , Jacques Patrícia Santos , Ziegler Bruna , Andrade Francini Porcher , de Tarso Roth Dalcin Paulo
Published: November 2020

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic lung disease characterized by progressive and irreversible changes of the bronchial tree. The evaluation of exercise capacity is essential to manage this disease. This study aims to determine the within-subject repeatability of two Six Minute Walk Test (6MWT) in adults with NCFB. NCFB. This cross-sectional observational study included 66 NCFB subjects above 18 years-old (mean of 55 ± 17 years old, 68% women). 73% of the participants presented moderate to severe clinical condition classified by Bronchiectasis Severity Index. It showed that these participants walked 16.6 m less (95%CI 3.8 to 29.4; p < 0.01) in the second 6MWT when compared to the first test, with a within-subject coefficient variation of 9.4% (95%CI 7.2–11.2%) and an intra-test reliability with a high intraclass correlation coefficient of 0.88 (95%CI 0.80–0.93). Bland–Altman plot showed an agreement regarding test repeatability, besides presented a large limit of agreement (− 85 to 116 m). Respiratory rate and systolic blood pressure were significantly higher before starting the second test. In conclusion, 6MWT seems to be reproducible in NCFB subjects and vital sign verification should be attentively checked to assess if the patient is fully recovered to perform a second test, as well as the disease severity score. Other studies on this matter should be conducted with a larger number of participants to confirm the findings of the present study.
The influence of breeding history, origin and growth type on population structure of barley as revealed by SSR markers
Authors: Mohammadi Seyyed Abolghasem , Abdollahi Sisi Nayyer , Sadeghzadeh Behzad
Published: November 2020

Natural and mass selection during domestication and cultivation favored particular traits of interest in barley. In the present study, population structure, and genetic relationships among 144 accessions of barley landraces and breeding materials from various countries were studied using a set of 77 and 72 EST-SSR and gSSR markers, respectively distributed on seven chromosomes of barley. In total, 262 and 429 alleles were amplified in 77 EST-SSRs and 72 gSSR loci, respectively. Out of which, 185 private/group-specific alleles were identified in the landraces compared with 14 in "cultivar and advanced breeding lines", indicating the possibility to introgress favorite alleles from landraces into breeding materials. Comparative analysis of genetic variation among breeding materials, Iranian landraces, and exotic landraces revealed higher genetic diversity in Iranian landraces compared with others. A total of 37, 15, and 14 private/group-specific alleles were identified in Iranian landraces, exotic landraces, and breeding materials, respectively. The most likely groups for 144 barley genotypes were three as inferred using model- and distance-based clustering as well as principal coordinate analysis which assigned the landraces and breeding materials into separate groups. The distribution of alleles was found to be correlated with population structure, domestication history and eco-geographical factors. The high allelic richness in the studied set of barley genotype provides insights into the available diversity and allows the construction of core groups based on maximizing allelic diversity for use in barley breeding programs.
‘Barcode fishing’ for archival DNA from historical type material overcomes taxonomic hurdles, enabling the description of a new frog species
Authors: Scherz Mark D. , Rasolonjatovo Safidy M. , Köhler Jörn , Rancilhac Loïs , Rakotoarison Andolalao , Raselimanana Achille P. , Ohler Annemarie , Preick Michaela , Hofreiter Michael , Glaw Frank , Vences Miguel
Published: November 2020

Taxonomic progress is often hindered by intrinsic factors, such as morphologically cryptic species that require a broad suite of methods to distinguish, and extrinsic factors, such as uncertainties in the allocation of scientific names to species. These uncertainties can be due to a wide variety of factors, including old and poorly preserved type specimens (which contain only heavily degraded DNA or have lost important diagnostic characters), inappropriately chosen type specimens (e.g. juveniles without diagnostic characters) or poorly documented type specimens (with unprecise, incorrect, or missing locality data). Thanks to modern sequencing technologies it is now possible to overcome many such extrinsic factors by sequencing DNA from name-bearing type specimens of uncertain assignment and assigning these to known genetic lineages. Here, we apply this approach to frogs of theMantidactylus ambreensiscomplex, which was recently shown to consist of two genetic lineages supported by concordant differentiation in mitochondrial and nuclear genes. These lineages co-occur on the Montagne dʼAmbre Massif in northern Madagascar but appear to have diverged in allopatry. We use a recently published bait set based on three mitochondrial markers from all known Malagasy frog lineages to capture DNA sequences from the 127-year-old holotype ofMantidactylus ambreensisMocquard, 1895. With the obtained sequences we are able to assign the nameM. ambreensisto the lowland lineage, which is rather widespread in the rainforests of northern Madagascar, leaving the microendemic high-elevation lineage on Montagne d’Ambre in north Madagascar in need of description. We describe this species asMantidactylus ambonysp. nov., differing fromM. ambreensisin call parameters and a smaller body size. Thus, using target enrichment to obtain DNA sequence data from this old specimen, we were able to resolve the extrinsic (nomenclatural) hindrances to taxonomic resolution of this complex. We discuss the broad-scale versatility of this ‘barcode fishing’ approach, which can draw on the enormous success of global DNA barcoding initiatives to quickly and efficiently assign type specimens to lineages.
Gene expression of the heat stress response in bovine peripheral white blood cells and milk somatic cells in vivo
Authors: Garner J. B. , Chamberlain A. J. , Vander Jagt C. , Nguyen T. T. T. , Mason B. A. , Marett L. C. , Leury B. J. , Wales W. J. , Hayes B. J.
Published: November 2020

Heat stress in dairy cattle leads to reduction in feed intake and milk production as well as the induction of many physiological stress responses. The genes implicated in the response to heat stress in vivo are not well characterised. With the aim of identifying such genes, an experiment was conducted to perform differential gene expression in peripheral white blood cells and milk somatic cells in vivo in 6 Holstein Friesian cows in thermoneutral conditions and in 6 Holstein Friesian cows exposed to a short-term moderate heat challenge. RNA sequences from peripheral white blood cells and milk somatic cells were used to quantify full transcriptome gene expression. Genes commonly differentially expressed (DE) in both the peripheral white blood cells and in milk somatic cells were associated with the cellular stress response, apoptosis, oxidative stress and glucose metabolism. Genes DE in peripheral white blood cells of cows exposed to the heat challenge compared to the thermoneutral control were related to inflammation, lipid metabolism, carbohydrate metabolism and the cardiovascular system. Genes DE in milk somatic cells compared to the thermoneutral control were involved in the response to stress, thermoregulation and vasodilation. These findings provide new insights into the cellular adaptations induced during the response to short term moderate heat stress in dairy cattle and identify potential candidate genes (BDKRB1andSNORA19) for future research.
Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition
Authors: Han Bin , Chen Huashuai , Yao Yao , Liu Xiaomin , Nie Chao , Min Junxia , Zeng Yi , Lutz Michael W.
Published: November 2020

In this study, we split 2156 individuals from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data into two groups, establishing a phenotype of exceptional longevity & normal cognition versus cognitive impairment. We conducted a genome-wide association study (GWAS) to identify significant genetic variants and biological pathways that are associated with cognitive impairment and used these results to construct polygenic risk scores. We elucidated the important and robust factors, both genetic and non-genetic, in predicting the phenotype, using several machine learning models. The GWAS identified 28 significant SNPs at p-value $$< 3 \times 10^{-5}$$

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3
×

10

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5

significance level and we pinpointed four genes, ESR1, PHB, RYR3, GRIK2, that are associated with the phenotype though immunological systems, brain function, metabolic pathways, inflammation and diet in the CLHLS cohort. Using both genetic and non-genetic factors, four machine learning models have close prediction results for the phenotype measured in Area Under the Curve: random forest (0.782), XGBoost (0.781), support vector machine with linear kernel (0.780), and $$\ell _2$$

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2

penalized logistic regression (0.780). The top four important and congruent features in predicting the phenotype identified by these four models are: polygenic risk score, sex, age, and education.
Soil quality parameters vis-a-vis growth and yield attributes of sugarcane as influenced by integration of microbial consortium with NPK fertilizers
Authors: Shukla S. K. , Sharma Lalan , Jaiswal V. P. , Pathak A. D. , Tiwari Raghvendra , Awasthi S. K. , Gaur Asha
Published: November 2020

Intensive agriculture involving high crop intensity, unavailability of organics, and higher use of straight fertilizers causes imbalanced use and deficiencies of several other macro and micronutrients. Nutrients supply through the integration of microbial consortium containing Gluconacetobater diazotrophicus, Trichoderma harzianum, and Pseudomonas fluorescens can reduce the requirements on the one hand and can also increase the response of chemical fertilizers. Thus we had planned the present experiment with the objectives (i) to determine the effect of integrated application of microbial consortium (MC) and NPK fertilizer on soil quality parameters and crop growth and yield attributes and (ii) to assess the effect of integration on agronomic efficiency of N, P and K and find out the possibilities for reduction in applied doses of NPK, if any. Five treatments viz., T1; N0P0K0; T2: N75P13K25; T3: N150P26K50; T4: N75P13K25 + microbial consortium and T5: N150P26K50 + microbial consortium containing new strains of Trichoderma harzianum, Gluconcetobacter diazotrophicus, and Pseudomonas fluorescens (CFU 109–10 per ml liquid culture) were evaluated under four replications in a randomized block design (RBD). Experimental results indicated that integrating microbial consortium and NPK fertilizers' application proved effective in improving soil organic carbon, soil microbial population, microbial biomass carbon, microbial biomass nitrogen, and soil respiration. Integrated use of microbial consortium with NPK also improved the cation exchange capacity of soil and roots. However, the growth and yield attributes, nutrients uptake, sugarcane, and sugar yields also revealed a positive effect of microbial consortium's integrated application with NPK. The integration of MC and NPK also improved the agronomic efficiency of applied nutrients (NPK). Reduction of 50% NPK with these microbial consortia (Trichoderma harzianum, Gluconcetobacter diazotrophicus, and Pseudomonas fluorescens) was found better than the application of full NPK through chemical fertilizers. Thus application of N150P26K50 with microbial consortium can sustain soil fertility besides improving sugarcane and sugar yields in subtropical Indian conditions.
Influenza virus infection augments susceptibility to respiratory Yersinia pestis exposure and impacts the efficacy of antiplague antibiotic treatments
Authors: Vagima Yaron , Gur David , Erez Noam , Achdout Hagit , Aftalion Moshe , Levy Yinon , Zauberman Ayelet , Tidhar Avital , Gutman Hila , Lazar Shlomi , Israely Tomer , Paran Nir , Melamed Sharon , Brosh-Nissimov Tal , Chitlaru Theodor , Sagi Irit , Mamroud Emanuelle
Published: November 2020

Various respiratory viral infections in general and seasonal influenza in particular may increase the susceptibility to bacterial infections. Plague caused by Yersinia pestis endangers large populations during outbreaks or bioterrorism attacks. Recommended antibiotic countermeasures include well-established protocols based on animal studies and corroborated by effective treatment of human cases. Until now, prior exposure to viral respiratory infections was not taken into consideration when selecting the appropriate treatment for plague. Here, we show that as late as 25 days after exposure to influenza virus, convalescent mice still exhibited an increased susceptibility to sublethal doses of Y. pestis, presented with aberrant cytokine expression, and impaired neutrophil infiltration in the lungs. Increased levels of M2 alveolar macrophages and type II epithelial cells, as well as induction in metalloproteases expression and collagen and laminin degradation, suggested that the previous viral infection was under resolution, correlating with enhanced susceptibility to plague. Surprisingly, postexposure prophylaxis treatment with the recommended drugs revealed that ciprofloxacin was superior to doxycycline in mice recovering from influenza infection. These results suggest that after an influenza infection, the consequences, such as impaired immunity and lung tissue remodeling and damage, should be considered when treating subsequent Y. pestis exposure.
A rational experimental approach to identify correctly the working voltage window of aqueous-based supercapacitors
Authors: Nunes Willian G. , Freitas Bruno G. A. , Beraldo Renato M. , Filho Rubens Maciel , Da Silva Leonardo M. , Zanin Hudson
Published: November 2020

It is common to find in the literature different values for the working voltage window (WVW) range for aqueous-based supercapacitors. In many cases, even with the best intentions of the widening the operating voltage window, the measured current using the cyclic voltammetry (CV) technique includes a significant contribution from the irreversible Faradaic reactions involved in the water-splitting process, masked by fast scan rates. Sometimes even using low scan rates is hard to determine precisely the correct WVW of the aqueous-based electrochemical capacitor. In this sense, we discuss here the best practices to determine the WVW for capacitive current in an absence of water splitting using complementary techniques such as CV, chronoamperometry (CA), and the electrochemical impedance spectroscopy (EIS). To accomplish this end, we prepare and present a model system composed of multiwalled carbon nanotubes buckypaper electrodes housed in the symmetric coin cell and soaked with an aqueous-based electrolyte. The system electrochemical characteristics are carefully evaluated during the progressive enlargement of the cell voltage window. The presence of residual Faradaic current is verified in the transients from the CA study, as well as the impedance changes revealed by EIS as a function of the applied voltage, is discussed. We verify that an apparent voltage window of 2.0 V determined using the CV technique is drastically decreased to 1.2 V after a close inspection of the CA findings used to discriminate the presence of a parasitic Faradaic process. Some orientations are presented to instigate the establishment in the literature of some good scientific practices concerned with the reliable characterization of supercapacitors.
Historically unprecedented Northern Gulf of Mexico hurricane activity from 650 to 1250 CE
Authors: Rodysill Jessica R. , Donnelly Jeffrey P. , Sullivan Richard , Lane Philip D. , Toomey Michael , Woodruff Jonathan D. , Hawkes Andrea D. , MacDonald Dana , d’Entremont Nicole , McKeon Kelly , Wallace Elizabeth , van Hengstum Peter J.
Published: November 2020

Hurricane Michael (2018) was the first Category 5 storm on record to make landfall on the Florida panhandle since at least 1851 CE (Common Era), and it resulted in the loss of 59 lives and $25 billion in damages across the southeastern U.S. This event placed a spotlight on recent intense (exceeding Category 4 or 5 on the Saffir-Simpson Hurricane Wind Scale) hurricane landfalls, prompting questions about the natural range in variability of hurricane activity that the instrumental record is too short to address. Of particular interest is determining whether the frequency of recent intense hurricane landfalls in the northern Gulf of Mexico (GOM) is within or outside the natural range of intense hurricane activity prior to 1851 CE. In this study, we identify intense hurricane landfalls in northwest Florida during the past 2000 years based on coarse anomaly event detection from two coastal lacustrine sediment archives. We identified a historically unprecedented period of heightened storm activity common to four Florida panhandle localities from 650 to 1250 CE and a shift to a relatively quiescent storm climate in the GOM spanning the past six centuries. Our study provides long-term context for events like Hurricane Michael and suggests that the observational period 1851 CE to present may underrepresent the natural range in landfalling hurricane activity.
Omics approaches for conservation biology research on the bivalve Chamelea gallina
Authors: Carducci Federica , Biscotti Maria Assunta , Trucchi Emiliano , Giuliani Maria Elisa , Gorbi Stefania , Coluccelli Alessandro , Barucca Marco , Canapa Adriana
Published: November 2020

The striped venus (Chamelea gallina) is an important economic resource in the Mediterranean Basin; this species has exhibited a strong quantitative decline in the Adriatic Sea. The aim of this work was to provide a comprehensive view of the biological status ofC. gallinato elucidate the bioecological characteristics and genetic diversity of wild populations. To the best of our knowledge, this investigation is the first to perform a multidisciplinary study onC. gallinabased on two omics approaches integrated with histological, ecotoxicological, and chemical analyses and with the assessment of environmental parameters. The results obtained through RNA sequencing indicated that the striped venus has a notable ability to adapt to different environmental conditions. Moreover, the stock reduction exhibited by this species in the last 2 decades seems not to have negatively affected its genetic diversity. Indeed, the high level of genetic diversity that emerged from our ddRAD dataset analyses is ascribable to the high larval dispersal rate, which might have played a “compensatory role” on local fluctuations, conferring to this species a good adaptive potential to face the environmental perturbations. These findings may facilitate the efforts of conservation biologists to adopt ad hoc management plans for this fishery resource.
Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis
Authors: Ingvarsen Signe Z. , Gårdsvoll Henrik , van Putten Sander , Nørregaard Kirstine S. , Krigslund Oliver , Meilstrup Josephine A. , Tran Collin , Jürgensen Henrik J. , Melander Maria C. , Nielsen Carsten H. , Kjaer Andreas , Bugge Thomas H. , Engelholm Lars H. , Behrendt Niels
Published: November 2020

The membrane-anchored matrix metalloprotease MT1-MMP is a potent collagenolytic enzyme with a well-established role in extracellular matrix turnover and cellular invasion into collagen-rich tissues. MT1-MMP is highly expressed in various types of cancer and has been demonstrated to be directly involved in several stages of tumor progression, including primary tumor growth, angiogenesis, invasion and metastasis. Osteosarcoma is the most common type of primary bone cancer. This disease is characterized by invasive tumor growth, leading to extensive bone destruction, and metastasis to the lungs. The tumor cells in human osteosarcoma display a strong expression of MT1-MMP, but the role of MT1-MMP in osteosarcoma progression is currently unknown. In this study, we investigated the role of MT1-MMP during various stages of osteosarcoma development. We utilized an optimized orthotopic murine osteosarcoma model and human osteosarcoma cells in which the MT1-MMP gene was knocked out using CRISPR/Cas9. We observed a strong expression of MT1-MMP in wildtype cells of both primary tumors and lung metastases, but, surprisingly, MT1-MMP deficiency did not affect primary tumor growth, bone degradation or the formation and growth of lung metastases. We therefore propose that, unlike findings reported in other cancers, tumor-expressed MT1-MMP is dispensable for all stages of osteosarcoma progression.
Minimum and maximum energy for crystals of magnetic dipoles
Authors: Batle Josep , Ciftja Orion
Published: November 2020

Properties of many magnetic materials consisting of dipoles depend crucially on the nature of the dipole–dipole interaction. In the present work, we study systems of magnetic dipoles where the dipoles are arranged on various types of one-dimensional, two-dimensional and three-dimensional lattices. It is assumed that we are in the regime of strong dipole moments where a classical treatment is possible. We combine a new classical numerical approach in conjuncture with an ansatz for an energy decomposition method to study the energy stability of various magnetic configurations at zero temperature for systems of dipoles ranging from small to an infinite number of particles. A careful analysis of the data in the bulk limit allows us to identify very accurate minimum and maximum energy bounds as well as ground state configurations corresponding to various types of lattices. The results suggest stabilization of a particularly interesting ground state configuration consisting of three embedded spirals for the case of a two-dimensional hexagonal lattice.
3-O-sulfated heparan sulfate interactors target synaptic adhesion molecules from neonatal mouse brain and inhibit neural activity and synaptogenesis in vitro
Authors: Maïza Auriane , Sidahmed-Adrar Nazha , Michel Patrick P. , Carpentier Gilles , Habert Damien , Dalle Carine , Redouane Walid , Hamza Magda , van Kuppevelt TH , Ouidja Mohand Ouidir , Courty José , Chantepie Sandrine , Papy-Garcia Dulce , Stettler Olivier
Published: November 2020

Heparan sulfate (HS) chains, covalently linked to heparan sulfate proteoglycans (HSPG), promote synaptic development and functions by connecting various synaptic adhesion proteins (AP). HS binding to AP could vary according to modifications of HS chains by different sulfotransferases. 3-O-sulfotransferases (Hs3sts) produce rare 3-O-sulfated HSs (3S-HSs), of poorly known functions in the nervous system. Here, we showed that a peptide known to block herpes simplex virus by interfering with 3S-HSs in vitro and in vivo (i.e. G2 peptide), specifically inhibited neural activity, reduced evoked glutamate release, and impaired synaptic assembly in hippocampal cell cultures. A role for 3S-HSs in promoting synaptic assembly and neural activity is consistent with the synaptic interactome of G2 peptide, and with the detection of Hs3sts and their products in synapses of cultured neurons and in synaptosomes prepared from developing brains. Our study suggests that 3S-HSs acting as receptors for herpesviruses might be important regulators of neuronal and synaptic development in vertebrates.
Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death
Authors: Brenet Alexandre , Somkhit Julie , Hassan-Abdi Rahma , Yanicostas Constantin , Romain Christiane , Bar Olivier , Igert Alexandre , Saurat Dominique , Taudon Nicolas , Dal-Bo Gregory , Nachon Florian , Dupuis Nina , Soussi-Yanicostas Nadia
Published: November 2020

With millions of intoxications each year and over 200,000 deaths, organophosphorus (OP) compounds are an important public health issue worldwide. OP poisoning induces cholinergic syndrome, with respiratory distress, hypertension, and neuron damage that may lead to epileptic seizures and permanent cognitive deficits. Existing countermeasures are lifesaving but do not prevent long-lasting neuronal comorbidities, emphasizing the urgent need for animal models to better understand OP neurotoxicity and identify novel antidotes. Here, using diisopropylfluorophosphate (DFP), a prototypic and moderately toxic OP, combined with zebrafish larvae, we first showed that DFP poisoning caused major acetylcholinesterase inhibition, resulting in paralysis and CNS neuron hyperactivation, as indicated by increased neuronal calcium transients and overexpression of the immediate early genes fosab, junBa, npas4b, and atf3. In addition to these epileptiform seizure-like events, DFP-exposed larvae showed increased neuronal apoptosis, which were both partially alleviated by diazepam treatment, suggesting a causal link between neuronal hyperexcitation and cell death. Last, DFP poisoning induced an altered balance of glutamatergic/GABAergic synaptic activity with increased NR2B-NMDA receptor accumulation combined with decreased GAD65/67 and gephyrin protein accumulation. The zebrafish DFP model presented here thus provides important novel insights into the pathophysiology of OP intoxication, making it a promising model to identify novel antidotes.
A primer set for the rapid isolation of scFv fragments against cell surface antigens from immunised rats
Authors: Nannini Francesco , Parekh Farhaan , Wawrzyniecka Patrycja , Mekkaoui Leila , Righi Matteo , Dastjerdi Fatemeh V. , Yeung Jenny , Roddie Claire , Bai Yuchen , Ma Biao , Ferrari Mathieu , Onuoha Shimobi , Chester Kerry , Pule Martin
Published: November 2020

Antibody phage display is a powerful platform for discovery of clinically applicable high affinity monoclonal antibodies against a broad range of targets. Libraries generated from immunized animals offer the advantage of in vivo affinity-maturation of V regions prior to library generation. Despite advantages, few studies have described isolation of antibodies from rats using immune phage display. In our study, we describe a novel primer set, covering the full rat heavy chain variable and kappa light chain variable regions repertoire for the generation of an unbiased immune libraries. Since the immune repertoire of rats is poorly understood, we first performed a deep sequencing analysis of the V(D)J regions of VH and VLK genes, demonstrating the high abundance of IGVH2 and IGVH5 families for VH and IGVLK12 and IGVLK22 for VLK. The comparison of gene’s family usage in naïve rats have been used to validate the frequency’s distribution of the primer set, confirming the absence of PCR-based biases. The primers were used to generate and assemble a phage display library from human CD160-vaccinated rats. CD160 represents a valid therapeutic target as it has been shown to be expressed on chronic lymphocytic leukaemia cells and on the surface of newly formed vessels. We utilised a novel phage display panning strategy to isolate a high affinity pool (KD range: 0.399–233 nM) of CD160 targeting monoclonal antibodies. Subsequently, identified binders were tested for function as third generation Chimeric Antigen Receptors (CAR) T cells demonstrating specific cytolytic activity. Our novel primer set coupled with a streamlined strategy for phage display panning enable the rapid isolation and identification of high affinity antibodies from immunised rats. The therapeutic utility of these antibodies was demonstrated in CAR format.
Plasma extracellular vesicle miRNAs as potential biomarkers of superstimulatory response in cattle
Authors: Gad Ahmed , Sánchez José María , Browne John A. , Nemcova Lucie , Laurincik Jozef , Prochazka Radek , Lonergan Pat
Published: November 2020

The ability to predict superstimulatory response would be a beneficial tool in assisted reproduction. Using small RNAseq technology, we profiled extracellular vesicle microRNA (EV-miRNA) abundance in the blood plasma of heifers exhibiting variable responses to superstimulation. Estrous synchronized crossbred beef heifers (n = 25) were superstimulated and blood samples were collected from each heifer on Day 7 of consecutive unstimulated (U) and superstimulated (S) cycles. A subset of high (H) and low (L) responders was selected depending on their response to superstimulation and EV-miRNA profiles were analysed at both time-points in each heifer. Approximately 200 known miRNAs were detected in each sample with 144 commonly detected in all samples. A total of 12 and 14 miRNAs were dysregulated in UH vs. UL and in SH vs. SL heifers, respectively. Interestingly, miR-206 and miR-6517 exhibited the same differential expression pattern in H compared to L heifers both before and after superstimulation. Pathway analysis indicated that circadian rhythm and signaling pathways were among the top pathways enriched with genes targeted by dysregulated miRNAs in H vs. L responding heifers. In conclusion, heifers with divergent ovarian responses exhibited differential expression of plasma EV-miRNAs which may be used as a potential biomarker to predict superstimulation response.
Fabrication of silane-grafted graphene oxide and its effect on the structural, thermal, mechanical, and hysteretic behavior of polyurethane
Authors: Lee Joo Hyung , Kim Seong Hun
Published: November 2020

Incorporation of nanofillers into polyurethane (PU) is a promising technique for enhancing its thermal and mechanical properties. Silane grafting has been used as a surface treatment for the functionalization of graphene oxide (GO) with numerous reactive sites dispersed on its basal plane and edge. In this study, amine-grafted GO was prepared using silanization of GO with (3-aminopropyl)triethoxysilane. The functionalized graphene oxide (fGO) was characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy. Next, it was introduced in PU fabricated using polycaprolactone diol, castor oil, and hexamethylene diisocyanate. The fGO–PU nanocomposites were in turn characterized by FT-IR, X-ray diffraction, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and a universal testing machine. The results obtained from these analyses showed changes in structural thermal properties, as well as improved thermal stability and mechanical properties because of the strong interfacial adhesion between the fGO and the PU matrix.
Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus)
Authors: Samaha Georgina , Wade Claire M. , Beatty Julia , Lyons Leslie A. , Fleeman Linda M. , Haase Bianca
Published: November 2020

Diabetes mellitus, a common endocrinopathy affecting domestic cats, shares many clinical and pathologic features with type 2 diabetes in humans. In Australia and Europe, diabetes mellitus is almost four times more common among Burmese cats than in other breeds. As a genetically isolated population, the diabetic Australian Burmese cat provides a spontaneous genetic model for studying diabetes mellitus in humans. Studying complex diseases in pedigreed breeds facilitates tighter control of confounding factors including population stratification, allelic frequencies and environmental heterogeneity. We used the feline SNV array and whole genome sequence data to undertake a genome wide-association study and runs of homozygosity analysis, of a case–control cohort of Australian and European Burmese cats. Our results identified diabetes-associated haplotypes across chromosomes A3, B1 and E1 and selective sweeps across the Burmese breed on chromosomes B1, B3, D1 and D4. The locus on chromosome B1, common to both analyses, revealed coding and splice region variants in candidate genes,ANK1, EPHX2andLOXL2,implicated in diabetes mellitus and lipid dysregulation. Mapping this condition in Burmese cats has revealed a polygenic spectrum, implicating loci linked to pancreatic beta cell dysfunction, lipid dysregulation and insulin resistance in the pathogenesis of diabetes mellitus in the Burmese cat.
Increase in temperature enriches heat tolerant taxa in Aedes aegypti midguts
Authors: Onyango Gorreti Maria , Bialosuknia M. Sean , Payne F. Anne , Mathias Nicholas , Ciota T. Alexander , Kramer D. Laura
Published: November 2020

Insect midgut microbial symbionts have been considered as an integral component in thermal adaptation due to their differential thermal sensitivity. Altered midgut microbial communities can influence both insect physiology and competence for important vector-borne pathogens. This study sought to gain insights into how Aedes aegypti midgut microbes and life history traits are affected by increase in baseline diurnal temperature. Increase in temperature resulted in the enrichment of specific taxa with Bacillus being the most enriched. Bacillus is known to be heat tolerant. It also resulted in a dissimilar microbial assemblage (Bray–Curtis Index, PERMANOVA, F = 2.2063; R2 = 0.16706; P = 0.002) and reduced survivorship (Log-rank [Mantel-Cox] test, Chi-square = 35.66 df = 5, P < 0.0001). Blood meal intake resulted in proliferation of pathogenic bacteria such as Elizabethkingia in the midgut of the mosquitoes. These results suggest that alteration of temperature within realistic parameters such as 2 °C for Ae. aegypti in nature may impact the midgut microbiome favoring specific taxa that could alter mosquito fitness, adaptation and vector–pathogen interactions.
Genetic and comparative mapping of Lupinus luteus L. highlight syntenic regions with major orthologous genes controlling anthracnose resistance and flowering time
Authors: Lichtin Nicole , Salvo-Garrido Haroldo , Till Bradley , Caligari Peter D. S. , Rupayan Annally , Westermeyer Fernando , Olivos Marcos
Published: November 2020

Anthracnose susceptibility and ill-adapted flowering time severely affect Lupinus luteus yield, which has high seed protein content, is excellent for sustainable agriculture, but requires genetic improvement to fulfil its potential. This study aimed to (1) develop a genetic map; (2) define collinearity and regions of synteny with Lupinus angustifolius; and (3) map QTLs/candidate genes for anthracnose resistant and flowering time. A few linkage groups/genomic regions tended to be associated with segregation distortion, but did not affect the map. The developed map showed collinearity, and syntenic regions with L. angustifolius. Major QTLs were mapped in syntenic regions. Alleles from the wild parent and cultivar, explained 75% of the phenotypic variance for anthracnose resistance and 83% for early flowering, respectively. Marker sequences flanking the QTLs showed high homology with the Lanr1 gene and Flowering-locus-T of L. angustifolius. This suggests orthologous genes for both traits in the L. luteus genome. The findings are remarkable, revealing the potential to combine early flowering/anthracnose resistant in fulfilling yield capacity in L. luteus, and can be a major strategy in the genetic improvement and usage of this species for sustainable protein production. Allele sequences and PCR-marker tagging of these genes are being applied in marker assisted selection.
Deep learning approach for predicting functional Z-DNA regions using omics data
Authors: Beknazarov Nazar , Jin Seungmin , Poptsova Maria
Published: November 2020

Computational methods to predict Z-DNA regions are in high demand to understand the functional role of Z-DNA. The previous state-of-the-art method Z-Hunt is based on statistical mechanical and energy considerations about B- to Z-DNA transition using sequence information. Z-DNA CHiP-seq experiment results showed little overlap with Z-Hunt predictions implying that sequence information only is not sufficient to explain emergence of Z-DNA at different genomic locations. Adding epigenetic and other functional genomic mark-ups to DNA sequence level can help revealing the functional Z-DNA sites. Here we take advantage of the deep learning approach that can analyze and extract information from large volumes of molecular biology data. We developed a machine learning approach DeepZ that aggregates information from genome-wide maps of epigenetic markers, transcription factor and RNA polymerase binding sites, and chromosome accessibility maps. With the developed model we not only verify the experimental Z-DNA predictions, but also generate the whole-genome annotation, introducing new possible Z-DNA regions, which have not yet been found in experiments and can be of interest to the researchers from various fields.
Inhibition of inflammatory signaling in Pax5 mutant cells mitigates B-cell leukemogenesis
Authors: Isidro-Hernández Marta , Mayado Andrea , Casado-García Ana , Martínez-Cano Jorge , Palmi Chiara , Fazio Grazia , Orfao Alberto , Ribera Jordi , Ribera Josep Maria , Zamora Lurdes , Raboso-Gallego Javier , Blanco Oscar , Alonso-López Diego , De Las Rivas Javier , Jiménez Rafael , García Criado Francisco Javier , García Cenador María Begoña , Ramírez-Orellana Manuel , Cazzaniga Giovanni , Cobaleda César , Vicente-Dueñas Carolina , Sánchez-García Isidro
Published: November 2020

PAX5 is one of the most frequently mutated genes in B-cell acute lymphoblastic leukemia (B-ALL), and children with inherited preleukemic PAX5 mutations are at a higher risk of developing the disease. Abnormal profiles of inflammatory markers have been detected in neonatal blood spot samples of children who later developed B-ALL. However, how inflammatory signals contribute to B-ALL development is unclear. Here, we demonstrate that Pax5 heterozygosis, in the presence of infections, results in the enhanced production of the inflammatory cytokine interleukin-6 (IL-6), which appears to act in an autocrine fashion to promote leukemia growth. Furthermore, in vivo genetic downregulation of IL-6 in these Pax5 heterozygous mice retards B-cell leukemogenesis, and in vivo pharmacologic inhibition of IL-6 with a neutralizing antibody in Pax5 mutant mice with B-ALL clears leukemic cells. Additionally, this novel IL–6 signaling paradigm identified in mice was also substantiated in humans. Altogether, our studies establish aberrant IL6 expression caused by Pax5 loss as a hallmark of Pax5-dependent B-ALL and the IL6 as a therapeutic vulnerability for B-ALL characterized by PAX5 loss.
Spatial accessibility of general inpatient care in Germany: an analysis of surgery, internal medicine and neurology
Authors: Bauer Jan , Klingelhöfer Doris , Maier Werner , Schwettmann Lars , Groneberg David A.
Published: November 2020

Improving spatial accessibility to hospitals is a major task for health care systems which can be facilitated using recent methodological improvements of spatial accessibility measures. We used the integrated floating catchment area (iFCA) method to analyze spatial accessibility of general inpatient care (internal medicine, surgery and neurology) on national level in Germany determining an accessibility index (AI) by integrating distances, hospital beds and morbidity data. The analysis of 358 million distances between hospitals and population locations revealed clusters of lower accessibility indices in areas in north east Germany. There was a correlation of urbanity and accessibility up to r = 0.31 (p < 0.001). Furthermore, 10% of the population lived in areas with significant clusters of low spatial accessibility for internal medicine and surgery (neurology: 20%). The analysis revealed the highest accessibility for heart failure (AI = 7.33) and the lowest accessibility for stroke (AI = 0.69). The method applied proofed to reveal important aspects of spatial accessibility i.e. geographic variations that need to be addressed. However, for the majority of the German population, accessibility of general inpatient care was either high or at least not significantly low, which suggests rather adequate allocation of hospital resources for most parts of Germany.
Genetic profiling of Vietnamese population from large-scale genomic analysis of non-invasive prenatal testing data
Authors: Tran Ngoc Hieu , Vo Thanh Binh , Nguyen Van Thong , Tran Nhat-Thang , Trinh Thu-Huong Nhat , Pham Hong-Anh Thi , Dao Thi Hong Thuy , Nguyen Ngoc Mai , Van Yen-Linh Thi , Tran Vu Uyen , Vu Hoang Giang , Bui Quynh-Tram Nguyen , Vo Phuong-Anh Ngoc , Nguyen Huu Nguyen , Nguyen Quynh-Tho Thi , Do Thanh-Thuy Thi , Lam Nien Vinh , Ngoc Phuong Cao Thi , Truong Dinh Kiet , Nguyen Hoai-Nghia , Giang Hoa , Phan Minh-Duy
Published: November 2020

The under-representation of several ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in many populations. Cost and technology limitations remain the challenges in performing large-scale genome sequencing projects in many developing countries, including Vietnam. As one of the most rapidly adopted genetic tests, non-invasive prenatal testing (NIPT) data offers an alternative untapped resource for genetic studies. Here we performed a large-scale genomic analysis of 2683 pregnant Vietnamese women using their NIPT data and identified a comprehensive set of 8,054,515 single-nucleotide polymorphisms, among which 8.2% were new to the Vietnamese population. Our study also revealed 24,487 disease-associated genetic variants and their allele frequency distribution, especially 5 pathogenic variants for prevalent genetic disorders in Vietnam. We also observed major discrepancies in the allele frequency distribution of disease-associated genetic variants between the Vietnamese and other populations, thus highlighting a need for genome-wide association studies dedicated to the Vietnamese population. The resulted database of Vietnamese genetic variants, their allele frequency distribution, and their associated diseases presents a valuable resource for future genetic studies.
Force–velocity profile during vertical jump cannot be assessed using only bodyweight jump and isometric maximal voluntary contraction tasks
Authors: Šarabon Nejc , Kozinc Žiga , Marković Goran
Published: November 2020

Recently, the two-point method of force–velocity (F–V) profiling of multi-joint human movements has been introduced and validated. In this study, we investigated the validity of estimating the jumping F–V profile using only bodyweight jump and isometric maximal voluntary contraction (MVC) task. Participants (n = 30) performed 3 repetitions of squat (SJ) and counter-movement jumps (CMJ), each at loads that were progressively increased by 10 kg increments, with the number of loads depending on the individual’s ability. Then, 3 isometric MVC trials were performed in 3 knee angles (30°, 60° and 90°). F–V profiling of SJ and CMJ were performed using the multiple-point method, the two-point method, and the novel Jump-MVC method. The results showed poor to fair validity of the novel Jump-MVC method for assessing jumping F–V profile (most ICC < 0.5, most CV > 10%, significant systematic bias present, and the presence of proportional bias). The exception was the estimation of theoretical maximal power, which was highly valid for both SJ and CMJ (ICC = 0.91–0.95; CV = 5.0–6.3%). In contrast, validity of the two-point method was excellent (all ICC > 0.90; CV = 2–6%). Although additional studies are needed, present results suggest that the F–V profiling of vertical jumps should be performed using the two-point method with distal loads.