bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide-based vaccine successfully induces protective immunity against canine visceral leishmaniasis
Authors: Petitdidier Elodie , Pagniez Julie , Pissarra Joana , Holzmuller Philippe , Papierok Gérard , Vincendeau Philippe , Lemesre Jean-Loup , Bras-Gonçalves Rachel
Published: November 2019

Dogs are the main reservoir of zoonotic visceral leishmaniasis. Vaccination is a promising approach to help control leishmaniasis and to interrupt transmission of theLeishmaniaparasite. The promastigote surface antigen (PSA) is a highly immunogenic component ofLeishmaniaexcretory/secretory products. A vaccine based on three peptides derived from the carboxy-terminal part ofLeishmania amazonensisPSA and conserved amongLeishmaniaspecies, formulated with QA-21 as adjuvant, was tested on naive Beagle dogs in a preclinical trial. Four months after the full course of vaccination, dogs were experimentally infected withLeishmania infantumpromastigotes. Immunization of dogs with peptide-based vaccine conferred immunity against experimental infection withL. infantum. Evidence for macrophage nitric oxide production and anti-leishmanial activity associated with IFN-γ production by lymphocytes was only found in the vaccinated group. An increase in specific IgG2 antibodies was also measured in vaccinated dogs from 2 months after immunization. Additionally, after challenge withL. infantum, the parasite burden was significantly lower in vaccinated dogs than in the control group. These data strongly suggest that this peptide-based vaccine candidate generated cross-protection against zoonotic leishmaniasis by inducing a Th1-type immune response associated with production of specific IgG2 antibodies. This preclinical trial including a peptide-based vaccine against leishmaniasis clearly demonstrates effective protection in a natural host. This approach deserves further investigation to enhance the immunogenicity of the peptides and to consider the possible engineering of a vaccine targeting severalLeishmaniaspecies.
A manually denoised audio-visual movie watching fMRI dataset for the studyforrest project
Authors: Liu Xingyu , Zhen Zonglei , Yang Anmin , Bai Haohao , Liu Jia
Published: November 2019

The data presented here are related to the studyforrest project that uses the movie ‘Forrest Gump’ to map brain functions in a real-life context using functional magnetic resonance imaging (fMRI). However, neural-related fMRI signals are often small and confounded by various noise sources (i.e., artifacts) that makes searching for the signals induced by specific cognitive processes significantly challenging. To make neural-related signals stand out from the noise, the audio-visual movie watching fMRI dataset from the project was denoised by a combination of spatial independent component analysis and manual identification of signals or noise. Here, both the denoised data and the labeled decomposed components are shared to facilitate further study. Compared with the original data, the denoised data showed a substantial improvement in the temporal signal-to-noise ratio and provided a higher sensitivity in subsequent analyses such as in an inter-subject correlation analysis.
Author Correction: Globe-LFMC, a global plant water status database for vegetation ecophysiology and wildfire applications
Authors: Yebra Marta , Scortechini Gianluca , Badi Abdulbaset , Beget María Eugenia , Boer Matthias M. , Bradstock Ross , Chuvieco Emilio , Danson F. Mark , Dennison Philip , de Dios Victor Resco , Di Bella Carlos M. , Forsyth Greg , Frost Philip , Garcia Mariano , Hamdi Abdelaziz , He Binbin , Jolly Matt , Kraaij Tineke , Martín M. Pilar , Mouillot Florent , Newnham Glenn , Nolan Rachael H. , Pellizzaro Grazia , Qi Yi , Quan Xingwen , Riaño David , Roberts Dar , Sow Momadou , Ustin Susan
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Cerebral ischemia induces TRPC6 via HIF1α/ZEB2 axis in the glomerular podocytes and contributes to proteinuria
Authors: Nakuluri Krishnamurthy , Nishad Rajkishor , Mukhi Dhanunjay , Kumar Sireesh , Nakka Venkata P. , Kolligundla Lakshmi P. , Narne Parimala , Natuva Sai Sampath K. , Phanithi Prakash Babu , Pasupulati Anil K.
Published: November 2019

Podocytes are specialized cells of the glomerulus and key component of the glomerular filtration apparatus (GFA). GFA regulates the permselectivity and ultrafiltration of blood. The mechanism by which the integrity of the GFA is compromised and manifest in proteinuria during ischemic stroke remains enigmatic. We investigated the mechanism of ischemic hypoxia-induced proteinuria in a middle cerebral artery occlusion (MCAO) model. Ischemic hypoxia resulted in the accumulation of HIF1α in the podocytes that resulted in the increased expression of ZEB2 (Zinc finger E-box-binding homeobox 2). ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium. Elevated expression of TRPC6 elicited increased calcium influx and aberrant activation of focal adhesion kinase (FAK) in podocytes. FAK activation resulted in the stress fibers reorganization and podocyte foot process effacement. Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia raises intracellular calcium levels via TRPC6 and consequently altered podocyte structure and function thus contributes to proteinuria.
Sorghum bicolor x S. halepense interspecific hybridization is influenced by the frequency of 2n gametes in S. bicolor
Authors: Hodnett George L. , Ohadi Sara , Pugh N. Ace , Bagavathiannan Muthukumar V. , Rooney William L.
Published: November 2019

Tetraploid johnsongrass [Sorghum halepense (L.) Pers.] is a sexually-compatible weedy relative of diploid sorghum [Sorghum bicolor (L.) Moench]. To determine the extent of interspecific hybridization between male sterile grain sorghum and johnsongrass and the ploidy of their progeny, cytoplasmic (CMS), genetic (GMS) and chemically induced male sterile lines of Tx623 and Tx631 were pollinated with johnsongrass pollen. At maturity 1% and 0.07% of the developing seeds of Tx623 and Tx631 respectively were recovered. Ninety-one percent of recovered hybrids were tetraploid and two percent were triploid, the tetraploids resulting from 2n gametes present in the sorghum female parent. Their formation appears to be genotype dependent as more tetraploids were recovered from Tx623 than Tx631. Because a tetraploid sorghum x johnsongrass hybrid has a balanced genome, they are male and female fertile providing opportunities for gene flow between the two species. Given the differences in 2n gamete formation among Tx623 and Tx631, seed parent selection may be one way of reducing the likelihood of gene flow. These studies were conducted in controlled and optimum conditions; the actual outcrossing rate in natural conditions is expected to be much lower. More studies are needed to assess the rates of hybridization, fitness, and fertility of the progeny under field conditions.
Malaria predictions based on seasonal climate forecasts in South Africa: A time series distributed lag nonlinear model
Authors: Kim Yoonhee , Ratnam J. V. , Doi Takeshi , Morioka Yushi , Behera Swadhin , Tsuzuki Ataru , Minakawa Noboru , Sweijd Neville , Kruger Philip , Maharaj Rajendra , Imai Chisato Chrissy , Ng Chris Fook Sheng , Chung Yeonseung , Hashizume Masahiro
Published: November 2019

Although there have been enormous demands and efforts to develop an early warning system for malaria, no sustainable system has remained. Well-organized malaria surveillance and high-quality climate forecasts are required to sustain a malaria early warning system in conjunction with an effective malaria prediction model. We aimed to develop a weather-based malaria prediction model using a weekly time-series data including temperature, precipitation, and malaria cases from 1998 to 2015 in Vhembe, Limpopo, South Africa and apply it to seasonal climate forecasts. The malaria prediction model performed well for short-term predictions (correlation coefficient, r > 0.8 for 1- and 2-week ahead forecasts). The prediction accuracy decreased as the lead time increased but retained fairly good performance (r > 0.7) up to the 16-week ahead prediction. The demonstration of the malaria prediction process based on the seasonal climate forecasts showed the short-term predictions coincided closely with the observed malaria cases. The weather-based malaria prediction model we developed could be applicable in practice together with skillful seasonal climate forecasts and existing malaria surveillance data. Establishing an automated operating system based on real-time data inputs will be beneficial for the malaria early warning system, and can be an instructive example for other malaria-endemic areas.
Streamflow variations across the Andes (18°–55°S) during the instrumental era
Authors: Masiokas M. H. , Cara L. , Villalba R. , Pitte P. , Luckman B. H. , Toum E. , Christie D. A. , Le Quesne C. , Mauget S.
Published: November 2019

The rivers originating in the southern Andes (18°–55°S) support numerous ecosystems and a large number of human populations and socio-economic activities in the adjacent lowlands of Chile, Argentina and Bolivia. Here we show that ca. 75% of the total variance in the streamflow records from this extensive region can be explained by only eight spatially coherent patterns of variability. Five (three) of these Andean patterns exhibit extreme dry (wet) conditions in recent years, with strong interannual variations in northern Chile; long-term drying trends between 31° and 41°S; a transitional pattern in the central Patagonian Andes; and increasing trends in northwestern Argentina and southern Bolivia, the Fueguian Andes, and the eastern portion of the South Patagonian Icefield. Multivariate regression analyses show that large-scale indices of ENSO variability can predict 20% to 45% of annual runoff variability between 28° and 46°S. The influence of Antarctic and North Pacific indices becomes more relevant south of 43°S and in northwestern Argentina and southern Bolivia, respectively, but their overall skill as predictors of Andean streamflows is weak. The analyses provide relevant new information to improve understanding of the spatial coherence, the main temporal features, and the ocean-atmospheric forcings of surface runoff across the southern Andes.
First complete pterosaur from the Afro-Arabian continent: insight into pterodactyloid diversity
Authors: Kellner Alexander W. A. , Caldwell Michael W. , Holgado Borja , Vecchia Fabio M. Dalla , Nohra Roy , Sayão Juliana M. , Currie Philip J.
Published: November 2019

Despite being known from every continent, the geological record of pterosaurs, the first group of vertebrates to develop powered flight, is very uneven, with only a few deposits accounting for the vast majority of specimens and almost half of the taxonomic diversity. Among the regions that stand out for the greatest gaps of knowledge regarding these flying reptiles, is the Afro-Arabian continent, which has yielded only a small number of very fragmentary and incomplete materials. Here we fill part of that gap and report on the most complete pterosaur recovered from this continent, more specifically from the Late Cretaceous (~95 mya) Hjoûla Lagerstätte of Lebanon. This deposit is known since the Middle Ages for the exquisitely preserved fishes and invertebrates, but not for tetrapods, which are exceedingly rare. Mimodactylus libanensis gen. et sp. nov. differs from the other Afro-Arabian pterosaur species named to date and is closely related to the Chinese species Haopterus gracilis, forming a new clade of derived toothed pterosaurs. Mimodactylidae clade nov. groups species that are related to Istiodactylidae, jointly designated as Istiodactyliformes (clade nov.). Istiodactyliforms were previously documented only in Early Cretaceous sites from Europe and Asia, with Mimodactylus libanensis the first record in Gondwana.
Respiratory syncytial, parainfluenza and influenza virus infection in young children with acute lower respiratory infection in rural Gambia
Authors: Mackenzie Grant A. , Vilane Aminata , Salaudeen Rasheed , Hogerwerf Lenny , van den Brink Sharon , Wijsman Lisa A. , Overduin Pieter , Janssens Thierry K. S. , de Silva Thushan I. , van der Sande Marianne A. B. , Kampmann Beate , Meijer Adam
Published: November 2019

Respiratory viral infections contribute significantly to morbidity and mortality worldwide, but representative data from sub-Saharan Africa are needed to inform vaccination strategies. We conducted population-based surveillance in rural Gambia using standardized criteria to identify and investigate children with acute lower respiratory infection (ALRI). Naso- and oropharyngeal swabs were collected. Each month from February through December 2015, specimens from 50 children aged 2–23 months were randomly selected to test for respiratory syncytial (RSV), parainfluenza (PIV) and influenza viruses. The expected number of viral-associated ALRI cases in the population was estimated using statistical simulation that accounted for the sampling design. RSV G and F proteins and influenza hemagglutinin genes were sequenced. 2385 children with ALRI were enrolled, 519 were randomly selected for viral testing. One or more viruses were detected in 303/519 children (58.4%). RSV-A was detected in 237 and RSV-B in seven. The expected incidence of ALRI associated with RSV, PIV or influenza was 140 cases (95% CI, 131–149) per 1000 person-years; RSV incidence was 112 cases (95% CI, 102–122) per 1000 person-years. Multiple strains of RSV and influenza circulated during the year. RSV circulated throughout most of the year and was associated with eight times the number of ALRI cases compared to PIV or IV. Gambian RSV viruses were closely related to viruses detected in other continents. An effective RSV vaccination strategy could have a major impact on the burden of ALRI in this setting.
The use of biological seed coatings based on bacteriophages and polymers against Clavibacter michiganensis subsp. nebraskensis in maize seeds
Authors: Kimmelshue Chad , Goggi A. Susana , Cademartiri Rebecca
Published: November 2019

Biological control of bacteria with bacteriophages is a viable alternative to antibiotics. To be successful, biological control bacteriophages must be stable when exposed to the environment. Stabilization can be achieved through incorporation of bacteriophages into polymers and stabilizers that will be coated onto the seed. For this study, bacteriophages against Clavibacter michiganensis subsp. nebraskensis (Cmn), the causal agent of Goss’s wilt, were incorporated into polyvinyl polymers with alcohol, ether and pyrrolidone functional groups and coated onto maize (Zea mays L.) seeds. The objectives of this study were to evaluate polymers and stabilizers that can protect Clavibacter michiganensis subsp. nebraskensis (CN8) bacteriophages against dehydration during storage. Bacteriophages stability when coated on seed depended on the glass transition temperature (Tg), functional groups of the polymer, and the presence of stabilizers such as sugars and proteins. Polyvinyl alcohol (PVOH) provided the greatest stability for CN8 bacteriophages on seed when coatings did not contain a stabilizer. A possible reason for the greater stability of this coating is having a glass transition temperature (Tg) very close to ambient temperature. PVOH combined with whey protein isolate (WPI) maintained CN8 bacteriophage activity in storage for four months at 26 °C and seven months at 10 °C. This coating also significantly reduced bacterial loads in seedlings grown from contaminated seeds, without affecting seed germination. Bacteriophage-polymer coatings which are stable during drying and storage, and are compatible with biological systems, not only provide an alternative to traditional antibiotics in agriculture, but also provide options for food, environmental and medical applications.
Comparative study of flocculation and adsorption behaviour of water treatment proteins from Moringa peregrina and Moringa oleifera seeds
Authors: Nouhi Shirin , Kwaambwa Habauka M. , Gutfreund Philipp , Rennie Adrian R.
Published: November 2019

Trees of Moringa oleifera are the most widely exploited species of Moringa and proteins extracted from its seeds have been identified as the most efficient natural coagulant for water purification. Largely for climatic reasons, other Moringa species are more accessible in some regions and this paper presents a comparative study of the adsorption to different materials of the proteins extracted from seeds of Moringa peregrina and Moringa oleifera to explore their use as flocculating agents in regions where each is more readily accessible. Results showed that Moringa peregrina seed proteins had higher adsorption to alumina compared to silica, in contrast to opposite behavior for Moringa oleifera. Both species provide cationic proteins that can act as effective coagulants for the various impurities with different surface potential. Despite the considerable similarity of the amino acid composition, the seed proteins have significantly different adsorption and this presents the opportunity to improve processes by choosing the optimal species or combination of species depending on the type of impurity or possible development of separation processes.
Gender Differences in Familiar Face Recognition and the Influence of Sociocultural Gender Inequality
Authors: Mishra Maruti V. , Likitlersuang Jirapat , B Wilmer Jeremy , Cohan Sarah , Germine Laura , DeGutis Joseph M.
Published: November 2019

Are gender differences in face recognition influenced by familiarity and socio-cultural factors? Previous studies have reported gender differences in processing unfamiliar faces, consistently finding a female advantage and a female own-gender bias. However, researchers have recently highlighted that unfamiliar faces are processed less efficiently than familiar faces, which have more robust, invariant representations. To-date, no study has examined whether gender differences exist for familiar face recognition. The current study addressed this by using a famous faces task in a large, web-based sample of  > 2000 participants across different countries. We also sought to examine if differences varied by socio-cultural gender equality within countries. When examining raw accuracy as well when controlling for fame, the results demonstrated that there were no participant gender differences in overall famous face accuracy, in contrast to studies of unfamiliar faces. There was also a consistent own-gender bias in male but not female participants. In countries with low gender equality, including the USA, females showed significantly better recognition of famous female faces compared to male participants, whereas this difference was abolished in high gender equality countries. Together, this suggests that gender differences in recognizing unfamiliar faces can be attenuated when there is enough face learning and that sociocultural gender equality can drive gender differences in familiar face recognition.
Two Distinct Types of Sweat Profile in Healthy Subjects While Exercising at Constant Power Output Measured by a Wearable Sweat Sensor
Authors: Choi Dong-Hoon , Kitchen Grant , Kim Ji Soo , Li Yi , Kim Kain , Jeong In cheol , Nguyen Jane , Stewart Kerry J. , Zeger Scott L. , Searson Peter C.
Published: November 2019

Wearable sweat sensors have enabled real-time monitoring of sweat profiles (sweat concentration versus time) and could enable monitoring of electrolyte loss during exercise or for individuals working in extreme environments. To assess the feasibility of using a wearable sweat chloride sensor for real-time monitoring of individuals during exercise, we recorded and analyzed the sweat profiles of 50 healthy subjects while spinning at 75 Watts for 1 hour. The measured sweat chloride concentrations were in the range from 2.9–34 mM. The sweat profiles showed two distinct sweat responses: Type 1 (single plateau) and Type 2 (multiple plateaus). Subjects with Type 2 profiles had higher sweat chloride concentration and weight loss, higher maximum heart rate, and larger changes in heart rate and rating of perceived exertion during the trial compared to subjects with Type 1 profiles. To assess the influence of level of effort, we recorded sweat profiles for five subjects at 75 W, 100 W, and 125 W. While all five subjects showed Type 1 sweat profiles at 75 W, four of the subjects had Type 2 profiles at 125 W, showing an increase in sweat chloride with exercise intensity. Finally, we show that sweat profiles along with other physiological parameters can be used to predict fluid loss.
Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix
Authors: Sood Disha , Cairns Dana M. , Dabbi Jayanth M. , Ramakrishnan Charu , Deisseroth Karl , Black Lauren D. , Santaniello Sabato , Kaplan David L.
Published: November 2019

Brain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and astrocytes. Particularly, fetal brain tissue-derived ECM supported long-term maintenance of differentiated neurons, demonstrated by morphology, gene expression and secretome profiling. Astrocytes were evident within the second month of differentiation, and reactive astrogliosis was inhibited in brain ECM-enriched cultures when compared to unsupplemented cultures. Functional maturation of the differentiated hiNSCs within fetal ECM-enriched cultures was confirmed by calcium signaling and spectral/cluster analysis. Additionally, the study identified native biochemical cues in decellularized ECM with notable comparisons between fetal and adult brain-derived ECMs. The development of novel brain-specific biomaterials for generating mature in vitro brain models provides an important path forward for interrogation of neuron-glia interactions.
Pelvic lymph node dissection and its extent on survival benefit in prostate cancer patients with a risk of lymph node invasion >5%: a propensity score matching analysis from SEER database
Authors: Chen Junru , Wang Zhipeng , Zhao Jinge , Zhu Sha , Sun Guangxi , Liu Jiandong , Zhang Haoran , Zhang Xingming , Shen Pengfei , Shi Ming , Zeng Hao
Published: November 2019

Pelvic lymph node dissection (PLND) represents the gold standard for nodal staging in PCa and is recommended for patients with a probability of lymph node invasion (LNI) >5%. However, the therapeutic role of PLND and its extent remains a debate. In this study, data of 20,668 patients treated with radical prostatectomy (RP) with and without PLND from SEER database between 2010 and 2015 were retrospectively analyzed. All patients had a risk of LNI >5% according to 2012-Briganti nomogram. Propensity score matching (PSM) was performed to balance baseline characteristics between patients with and without PLND. Kaplan-Meier curves and Cox regression were used to evaluate the impacts of the PLND and its extent on cancer-specific survival (CSS) and overall survival (OS). In overall cohort, patients with PLND were associated with more aggressive clinicopathologic characteristics and had poorer survival compared to those without PLND (5-year CSS rate: 98.4% vs. 99.7%, p < 0.001; 5-year OS rate: 96.3% vs. 97.8%, p < 0.001). In the post-PSM cohort, no significant difference in survival was found between patients with and without PLND (5-year CSS rate: 99.4% vs. 99.7%, p = 0.479; 5-year OS rate: 97.3% vs. 97.8%, p = 0.204). In addition, the extent of PLND had no impact on prognosis (all p > 0.05). Subgroup analyses reported similar negative findings. In conclusion, neither PLND nor its extent was associated with survival in North American patients with a risk of LNI >5%. The cut-off point of 5% probability of LNI might be too low to show benefits in survival in patients underwent PLND.
Acylated Ghrelin and The Regulation of Lipid Metabolism in The Intestine
Authors: Auclair N. , Patey N. , Melbouci L. , Ou Y. , Magri-Tomaz L. , Sané A. , Garofalo C. , Levy E. , St-Pierre D. H.
Published: November 2019

Acylated ghrelin (AG) is a gastrointestinal (GI) peptide mainly secreted by the stomach that promotes cytosolic lipid droplets (CLD) hypertrophy in adipose tissues and liver. However, the role of AG in the regulation of lipid metabolism in the intestine remains unexplored. This study aimed at determining whether AG influences CLD production and chylomicron (CM) secretion in the intestine. The effects of AG and oleic acid on CLD accumulation and CM secretion were first investigated in cultured Caco-2/15 enterocytes. Intestinal lipid metabolism was also studied in Syrian Golden Hamsters submitted to conventional (CD) or Western (WD) diets for 8 weeks and continuously administered with AG or physiological saline for the ultimate 2 weeks. In cultured Caco-2/15 enterocytes, CLD accumulation influenced CM secretion while AG reduced fatty acid uptake. In WD hamsters, continuous AG treatment amplified chylomicron output while reducing postprandial CLD accumulation in the intestine. The present study supports the intimate relationship between CLD accumulation and CM secretion in the intestine and it underlines the importance of further characterizing the mechanisms through which AG exerts its effects on lipid metabolism in the intestine.
Association between lipid profiles and presence of carotid plaque
Authors: Liu Yanhua , Zhu Yongjian , Jia Wenrui , Sun Dan , Zhao Li , Zhang Chen , Wang Cuicui , Chen Gaiyun , Fu Sanxian , Bo Yacong , Xing Yurong
Published: November 2019

It is indicated that lipids profiles are associated with carotid plaque and Atherosclerosis. However, studies about the relationship between serum lipid profiles and carotid plaque composition in Chinese Population is limited. We conducted a cross-sectional study among 3,214 participants between January 2015 and December 2017 in China, to investigate the association between various lipid profiles and the prevalence of carotid plaque. Logistic regression model was used to investigate the association between plasma lipid profiles and odds of carotid plaque. Analysis of covariance (ANCOVA) was used to compare the mean plasma lipid profiles among different number and composition of carotid artery plaques. HDL-C, Non-HDL-C levels, TC/HDL-C, LDL-C/HDL-C were significantly associated with the presence of carotid plaque; HDL-C, LDL-C, Non-HDL-C levels, TC/HDL-C, LDL-C/HDL-C were significantly associated with the presence of common carotid artery (CCA) plaque. Compare with participants without carotid plaque, increased level of LDL-C/HDL-C was found in those with echolucent/polytype plaque. Similarly, compared with participants without CCA plaque, increased level of LDL-C/HDL-C was found in those with echolucent plaque. In conclusion, we found that serum HDL-C, Non-HDLc level, TC/HDLc, and LDLc/HDLc were all associated with the prevalence of carotid plaque, and LDL-C/HDL-C differed among different group of carotid plaque composition.
Structural and functional role of disulphide bonds and substrate binding residues of the human beta-galactoside alpha-2,3-sialyltransferase 1 (hST3Gal1)
Authors: Ortiz-Soto Maria Elena , Reising Sabine , Schlosser Andreas , Seibel Jürgen
Published: November 2019

Overexpression of hST3Gal1 leads to hypersialylation of cell-surface glycoconjugates, a cancer-associated condition that promotes cell growth, migration and invasion. Upregulation of this enzyme in ovarian cancer is linked to cancer progression and metastasis, contributing also to chemotherapy resistance. Strategies for preventing metastasis include the inhibition of hST3Gal1, which demands structure-based studies on its strict regioselectivity and substrate/donor preference. Herein we describe the contribution of various residues constituting donor CMP-Neu5Ac and acceptor Galβ1-3GalNAc-R binding sites to catalysis. Removal of hydrogen bonds and/or stacking interactions among substrates and residues Y191, Y230, N147, S148 and N170 affected the enzyme’s activity to a different extent, revealing the fine control needed for an optimal catalytic performance. To gain further understanding of the correlation among structure, activity and stability, the in vitro role of hST3Gal1 disulphide bonds was analysed. As expected, disruption of the Glycosyltransferase family 29 (GT29) invariant bond C142-C281, as well as the ST3Gal1 subfamily conserved disulphide C61-C139 inactivates the enzyme. While disulphide C59-C64 is not essential for function, its absence reduces the activity (kcat) for donor and acceptor substrates to about 67 and 72%, respectively, and diminishes the enzyme’s melting temperature (Tm) by 7 °C.
NNTox: Gene Ontology-Based Protein Toxicity Prediction Using Neural Network
Authors: Jain Aashish , Kihara Daisuke
Published: November 2019

With advancements in synthetic biology, the cost and the time needed for designing and synthesizing customized gene products have been steadily decreasing. Many research laboratories in academia as well as industry routinely create genetically engineered proteins as a part of their research activities. However, manipulation of protein sequences could result in unintentional production of toxic proteins. Therefore, being able to identify the toxicity of a protein before the synthesis would reduce the risk of potential hazards. Existing methods are too specific, which limits their application. Here, we extended general function prediction methods for predicting the toxicity of proteins. Protein function prediction methods have been actively studied in the bioinformatics community and have shown significant improvement over the last decade. We have previously developed successful function prediction methods, which were shown to be among top-performing methods in the community-wide functional annotation experiment, CAFA. Based on our function prediction method, we developed a neural network model, named NNTox, which uses predicted GO terms for a target protein to further predict the possibility of the protein being toxic. We have also developed a multi-label model, which can predict the specific toxicity type of the query sequence. Together, this work analyses the relationship between GO terms and protein toxicity and builds predictor models of protein toxicity.
Highly cooperative fluorescence switching of self-assembled squaraine dye at tunable threshold temperatures using thermosensitive nanovesicles for optical sensing and imaging
Authors: Sou Keitaro , Chan Li Yan , Arai Satoshi , Lee Chi-Lik Ken
Published: November 2019

Thermosensitive fluorescent dyes can convert thermal signals into optical signals as a molecular nanoprobe. These nanoprobes are playing an increasingly important part in optical temperature sensing and imaging at the nano- and microscale. However, the ability of a fluorescent dye itself has sensitivity and accuracy limitations. Here we present a molecular strategy based on self-assembly to overcome such limitations. We found that thermosensitive nanovesicles composed of lipids and a unique fluorescent dye exhibit fluorescence switching characteristics at a threshold temperature. The switch is rapid and reversible and has a high signal to background ratio (>60), and is also highly sensitive to temperature (10–22%/°C) around the threshold value. Furthermore, the threshold temperature at which fluorescence switching is induced, can be tuned according to the phase transition temperature of the lipid bilayer membrane forming the nanovesicles. Spectroscopic analysis indicated that the fluorescence switching is induced by the aggregation-caused quenching and disaggregation-induced emission of the fluorescent dye in a cooperative response to the thermotropic phase transition of the membrane. This mechanism presents a useful approach for chemical and material design to develop fluorescent nanomaterials with superior fluorescence sensitivity to thermal signals for optical temperature sensing and imaging at the nano- and microscales.
Influence of age and gender on the pulse waveform in optic nerve head circulation in healthy men and women
Authors: Kobayashi Tatsuhiko , Shiba Tomoaki , Nishiwaki Yuji , Kinoshita Ayako , Matsumoto Tadashi , Hori Yuichi
Published: November 2019

The influences of age and gender differences on the pulse waveform in the optic nerve head (ONH) in healthy adults, using laser speckle flowgraphy (LSFG) were evaluated. We studied 908 healthy subjects (men = 701, age: 50.0 ± 9.1, women = 208, age: 49.8 ± 9.5, p = 0.76), evaluating these pulse waveform parameters: the blowout score (BOS), blowout time (BOT), acceleration time index (ATI), and the rising and falling rates. The parameters were analyzed separately for the tissue, vessels, and throughout the optic nerve head (All). All parameters were compared between genders. We investigated which independent factors for the pulse waveform in the ONH is most strongly correlated with age. All sections of the BOS, BOT, ATI, and falling rate showed a significant gender difference. A univariate regression analysis revealed that BOT-Tissue showed the strongest correlation with age (r = −0.51). The factors contributing independently to the BOT-Tissue were gender, age, heart rate, mean arterial blood pressure, pulse pressure, spherical refraction, and estimated glomerular filtration rate. Among the subjects aged >41 years, the chronological changes of BOT-Tissue in the women were significantly lower than those in the men. We concluded that the pulse waveform in the ONH has clear differences between the genders and shows chronological changes.
Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies
Authors: Montigaud Yoann , Périnel-Ragey Sophie , Plantier Laurent , Leclerc Lara , Goy Clémence , Clotagatide Anthony , Prévôt Nathalie , Pourchez Jérémie
Published: November 2019

Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81mKr gas-ventilation and 99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.
Hat1 acetylates histone H4 and modulates the transcriptional program in Drosophila embryogenesis
Authors: Varga Júlia , Korbai Szabina , Neller Alexandra , Zsindely Nóra , Bodai László
Published: November 2019

Post-translational modifications of histone proteins play a pivotal role in DNA packaging and regulation of genome functions. Histone acetyltransferase 1 (Hat1) proteins are conserved enzymes that modify histones by acetylating lysine residues. Hat1 is implicated in chromatin assembly and DNA repair but its role in cell functions is not clearly elucidated. We report the generation and characterization of a Hat1 loss-of-function mutant in Drosophila. Hat1 mutants are viable and fertile with a mild sub-lethal phenotype showing that Hat1 is not essential in fruit flies. Lack of Hat1 results in the near complete loss of histone H4 lysine (K) 5 and K12 acetylation in embryos, indicating that Hat1 is the main acetyltransferase specific for these marks in this developmental stage. We found that Hat1 function and the presence of these acetyl marks are not required for the nuclear transport of histone H4 as histone variant His4r retained its nuclear localization both in Hat1 mutants and in His4r-K5R-K12R double point mutants. RNA-seq analysis of embryos indicate that in Hat1 mutants over 2000 genes are dysregulated and the observed transcriptional changes imply a delay in the developmental program of gene expression.
Siloxane-functionalised surface patterns as templates for the ordered deposition of thin lamellar objects
Authors: Hoffmann Julian , Gamboa Sofia Madrigal , Hofmann Andreas , Gliemann Hartmut , Welle Alexander , Wacker Irene , Schröder Rasmus R. , Ness Len , Hagenmeyer Veit , Gengenbach Ulrich
Published: November 2019

A novel method is demonstrated for ordered deposition of thin lamellar objects from a liquid environment onto solid substrates by solid/fluid/solid-driven organisation. Surface functionalisation forms a template pattern that accumulates the lamellar objects by site-selective wetting of the target area without the need for a physical fluid containment. Contrary to conventional handling methods, no mechanical contact occurs, which facilitates the ordered deposition without wrinkles or ruptures. An additive and a subtractive process for the creation of such templates are presented. The subtractive process starts with the complete silanisation of the substrate in the vapour phase followed by site-selective oxygen plasma treatment of the siloxane film. The additive process uses microcontact printing to transfer the target pattern. Both processes are characterised by optical inspection of the wetting contours and it is found that site-selective plasma treatment shows a better pattern fidelity. The patterns obtained by site-selective plasma treatment are also subject to ToF-SIMS analysis and show good chemical contrast between hydrophilic and hydrophobic areas. The ordered deposition of lamellar objects by this new method is demonstrated for 60 nm thick ultramicrotome sections of epoxide resin on pre-patterned glass substrates.
Relationships of blood proinflammatory markers with psychological resilience and quality of life in civilian women with posttraumatic stress disorder
Authors: Imai Risa , Hori Hiroaki , Itoh Mariko , Lin Mingming , Niwa Madoka , Ino Keiko , Ogawa Sei , Sekiguchi Atsushi , Kunugi Hiroshi , Akechi Tatsuo , Kamo Toshiko , Kim Yoshiharu
Published: November 2019

Individuals with posttraumatic stress disorder (PTSD) show low resilience and impaired quality of life (QOL). Accumulating evidence shows that PTSD is associated with increased inflammation. Studies suggest that inflammation can be a key mechanism underlying low resilience/QOL, but this relationship has been understudied in individuals with PTSD. Here, we investigated the association of blood proinflammatory markers with self-reported resilience and QOL in civilian women with PTSD. Fifty-six women with PTSD and 73 healthy control women participated in this study. Resilience was assessed using the Connor-Davidson Resilience Scale. QOL was assessed using the World Health Organization Quality of Life-BREF. Blood samples were collected for the measurement of three proinflammatory markers including interleukin-6 (IL-6), high-sensitivity tumor necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Compared to controls, patients showed significantly higher IL-6 levels and lower resilience and QOL. In patients, IL-6 levels were significantly negatively correlated with resilience, and hsCRP levels were significantly negatively correlated with psychological QOL. These results show that increased levels of proinflammatory markers including IL-6 and hsCRP are associated with lower psychological resilience and QOL in PTSD patients. Our findings suggest that interventions and treatments targeting inflammation may aid in the recovery from PTSD and lead to better prognosis.
Production of monodisperse polyurea microcapsules using microfluidics
Authors: Thorne Michael F. , Simkovic Felix , Slater Anna G.
Published: November 2019

Methods to make microcapsules – used in a broad range of healthcare and energy applications – currently suffer from poor size control, limiting the establishment of size/property relationships. Here, we use microfluidics to produce monodisperse polyurea microcapsules (PUMC) with a limonene core. Using varied flow rates and a commercial glass chip, we produce capsules with mean diameters of 27, 30, 32, 34, and 35 µm, achieving narrow capsule size distributions of ±2 µm for each size. We describe an automated method of sizing droplets as they are produced using video recording and custom Python code. The sustainable generation of such size-controlled PUMCs, potential replacements for commercial encapsulated systems, will allow new insights into the effect of particle size on performance.
Experimental Protein Molecular Dynamics: Broadband Dielectric Spectroscopy coupled with nanoconfinement
Authors: Bourgeat Laëtitia , Serghei Anatoli , Lesieur Claire
Published: November 2019

Protein dynamics covers multiple spatiotemporal scale processes, among which slow motions, not much understood even though they are underlying protein folding and protein functions. Protein slow motions are associated with structural heterogeneity, short-lived and poorly populated conformations, hard to detect individually. In addition, they involve collective motions of many atoms, not easily tracked by simulation and experimental devices. Here we propose a biophysical approach, coupling geometrical nanoconfinement and broadband dielectric spectroscopy (BDS), which distinguishes protein conformations by their respective molecular dynamics. In particular, protein-unfolding intermediates, usually poorly populated in macroscopic solutions are detected. The protein dynamics is observed under unusual conditions (sample nanoconfinement and dehydration) highlighting the robustness of protein structure and protein dynamics to a variety of conditions consistent with protein sustainability. The protein dielectric signals evolve with the temperature of thermal treatments indicating sensitivity to atomic and molecular interaction changes triggered by the protein thermal unfolding. As dipole fluctuations depend on both collective large-scale motions and local motions, the approach offers a prospect to track in-depth unfolding events.
Publisher Correction: Real-time magnetic resonance imaging – guided coronary intervention in a porcine model
Authors: Heidt Timo , Reiss Simon , Krafft Axel J. , Özen Ali Caglar , Lottner Thomas , Hehrlein Christoph , Galmbacher Roland , Kayser Gian , Hilgendorf Ingo , Stachon Peter , Wolf Dennis , Zirlik Andreas , Düring Klaus , Zehender Manfred , Meckel Stephan , von Elverfeldt Dominik , Bode Christoph , Bock Michael , von zur Mühlen Constantin
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice
Authors: Kaneko Kazumasa B. , Tateishi Ryosuke , Miyao Takahisa , Takakura Yuki , Akiyama Nobuko , Yokota Ryo , Akiyama Taishin , Kobayashi Tetsuya J.
Published: November 2019

Thymic crosstalk, a set of reciprocal regulations between thymocytes and the thymic environment, is relevant for orchestrating appropriate thymocyte development as well as thymic recovery from various exogenous insults. In this work, interactions shaping thymic crosstalk and the resultant dynamics of thymocytes and thymic epithelial cells are inferred based on quantitative analysis and modeling of the recovery dynamics induced by irradiation. The analysis identifies regulatory interactions consistent with known molecular evidence and reveals their dynamic roles in the recovery process. Moreover, the analysis also predicts, and a subsequent experiment verifies, a previously unrecognized regulation of CD4+CD8+ double positive thymocytes which temporarily increases their proliferation rate upon the decrease in their population size. Our model establishes a pivotal step towards the dynamic understanding of thymic crosstalk as a regulatory network system.
Extensive host-switching of avian feather lice following the Cretaceous-Paleogene mass extinction event
Authors: de Moya Robert S. , Allen Julie M. , Sweet Andrew D. , Walden Kimberly K. O. , Palma Ricardo L. , Smith Vincent S. , Cameron Stephen L. , Valim Michel P. , Galloway Terry D. , Weckstein Jason D. , Johnson Kevin P.
Published: November 2019

Nearly all lineages of birds host parasitic feather lice. Based on recent phylogenomic studies, the three major lineages of modern birds diverged from each other before the Cretaceous-Paleogene (K-Pg) mass extinction event. In contrast, studies of the phylogeny of feather lice on birds, indicate that these parasites diversified largely after this event. However, these studies were unable to reconstruct the ancestral avian host lineage for feather lice. Here we use genome sequences of a broad diversity of lice to reconstruct a phylogeny based on 1,075 genes. By comparing this louse evolutionary tree to the avian host tree, we show that feather lice began diversifying on the common ancestor of waterfowl and landfowl, then radiated onto other avian lineages by extensive host-switching. Dating analyses and cophylogenetic comparisons revealed that two of three lineages of birds that diverged before the K-Pg boundary acquired their feather lice after this event via host-switching.
Bioinspired networks consisting of spongy carbon wrapped by graphene sheath for flexible transparent supercapacitors
Authors: Nguyen Duc Dung , Hsiao Chung-Hsuan , Su Teng-Yu , Hsieh Ping-Yen , Chen Yu-Ling , Chueh Yu-Lun , Lee Chi-Young , Tai Nyan-Hwa
Published: November 2019

Hierarchically ordered structures with low tortuosity, excellent mechanical flexibility, high optical transparency, and outstanding electrical conductivity are critically important in developing flexible transparent supercapacitor electrodes for innovative applications in electronics and displays. Here a CVD process is employed to fabricate leaf-skeleton inspired electrodes, which are reticulated monolithic networks consisting of carbon nanostructures serving as a 3D spongy core and graphene-based films as a protective/conductive shell. The network electrodes show optical transmittance of 85–88%, an electrical sheet resistance of ~1.8 Ω/sq, and an areal capacitance of 7.06 mF cm−2 (at 0.78 mA cm−2 in a three-electrode cell) in Na2SO4 aqueous electrolyte. Flexible transparent and symmetric supercapacitors, based on PVA/H3PO4 gel and the network electrodes, possess a stable working voltage of 1.6 V, energy and power density of 0.068 μWh cm−2 and 47.08 μW cm−2 at an optical transparency of ~80%, and no capacitance loss over 30,000 flat-bend-release cycles.