bluuebunny/crossref_metadata_2025 huggingface dataset:
Response analysis of host Spodoptera exigua larvae to infection by Heliothis virescens ascovirus 3h (HvAV-3h) via transcriptome
Authors: Yu Huan , Li Zi-Qi , He Lei , Ou-Yang Yi-Yi , Li Ni , Huang Guo-Hua
Published: March 2018

Heliothis virescens ascovirus 3 h (HvAV-3h), a dsDNA insect virus, belonging to the family Ascoviridae, can infect caterpillars of several Noctuidae species by ovipositing parasitoid wasps. In order to provide a comprehensive overview of the interactive responses of host larvae after infection by the ascovirus, a transcriptome analysis of Spodoptera exigua to HvAV-3h was conducted from 6 to 168 hours post infection (hpi). Approximately 101.64 Gb of RNA sequencing (RNA-seq) data obtained from infected and uninfected S. exigua larvae were used to perform a de novo transcriptome assembly, which generated approximately 62,258 S. exigua unigenes. Using differential gene expression analysis, it was determined that the majority of host transcripts were down-regulated beginning at 6 hpi and continuing throughout the infection period, although there was an increase in up-regulated unigene number during the 12 to 72 hpi stage. It is noteworthy that the most abundantly enriched pathways in KEGG annotation were Metabolism terms, indicating that the host larval metabolic mechanisms were highly influenced post HvAV-3h infection. In addition, the host cuticle protein encoding unigenes were highly down-regulated in most of the situations, suggesting that the host larval cuticle synthesis were inhibited by the viral infection.
Mechanism of translation control of the alternative Drosophila melanogaster Voltage Dependent Anion-selective Channel 1 mRNAs
Authors: Leggio L. , Guarino F. , Magrì A. , Accardi-Gheit R. , Reina S. , Specchia V. , Damiano F. , Tomasello M. F. , Tommasino M. , Messina A.
Published: March 2018

The eukaryotic porin, also called the Voltage Dependent Anion-selective Channel (VDAC), is the main pore-forming protein of the outer mitochondrial membrane. In Drosophila melanogaster, a cluster of genes evolutionarily linked to VDAC is present on chromosome 2L. The main VDAC isoform, called VDAC1 (Porin1), is expressed from the first gene of the cluster. The porin1 gene produces two splice variants, 1A-VDAC and 1B-VDAC, with the same coding sequence but different 5′ untranslated regions (UTRs). Here, we studied the influence of the two 5′ UTRs, 1A-5′ UTR and 1B-5′ UTR, on transcription and translation of VDAC1 mRNAs. In porin-less yeast cells, transformation with a construct carrying 1A-VDAC results in the expression of the corresponding protein and in complementation of a defective cell phenotype, whereas the 1B-VDAC sequence actively represses VDAC expression. Identical results were obtained using constructs containing the two 5′ UTRs upstream of the GFP reporter. A short region of 15 nucleotides in the 1B-5′ UTR should be able to pair with an exposed helix of 18S ribosomal RNA (rRNA), and this interaction could be involved in the translational repression. Our data suggest that contacts between the 5′ UTR and 18S rRNA sequences could modulate the translation of Drosophila 1B-VDAC mRNA. The evolutionary significance of this finding is discussed.
Recruitment kinetics of the homologous recombination pathway in procyclic forms of Trypanosoma brucei after ionizing radiation treatment
Authors: Marin Paula Andrea , da Silva Marcelo Santos , Pavani Raphael Souza , Machado Carlos Renato , Elias Maria Carolina
Published: March 2018

One of the most important mechanisms for repairing double-strand breaks (DSBs) in model eukaryotes is homologous recombination (HR). Although the genes involved in HR have been found in Trypanosoma brucei and studies have identified some of the proteins that participate in this HR pathway, the recruitment kinetics of the HR machinery onto DNA during DSB repair have not been clearly elucidated in this organism. Using immunofluorescence, protein DNA-bound assays, and DNA content analysis, we established the recruitment kinetics of the HR pathway in response to the DSBs generated by ionizing radiation (IR) in procyclic forms of T. brucei. These kinetics involved the phosphorylation of histone H2A and the sequential recruitment of the essential HR players Exo1, RPA, and Rad51. The process of DSB repair took approximately 5.5 hours. We found that DSBs led to a decline in the G2/M phase after IR treatment, concomitant with cell cycle arrest in the G1/S phase. This finding suggests that HR repairs DSBs faster than the other possible DSB repair processes that act during the G1/S transition. Taken together, these data suggest that the interplay between DNA damage detection and HR machinery recruitment is finely coordinated, allowing these parasites to repair DNA rapidly after DSBs during the late S/G2 proficient phases.
Acute metabolic actions of the major polyphenols in chamomile: an in vitro mechanistic study on their potential to attenuate postprandial hyperglycaemia
Authors: Villa-Rodriguez Jose A. , Kerimi Asimina , Abranko Laszlo , Tumova Sarka , Ford Lauren , Blackburn Richard S. , Rayner Christopher , Williamson Gary
Published: March 2018

Transient hyperglycaemia is a risk factor for type 2 diabetes and endothelial dysfunction, especially in subjects with impaired glucose tolerance. Nutritional interventions and strategies for controlling postprandial overshoot of blood sugars are considered key in preventing progress to the disease state. We have identified apigenin-7-O-glucoside, apigenin, and (Z) and (E)−2-hydroxy-4-methoxycinnamic acid glucosides as the active (poly)phenols in Chamomile (Matricaria recutita) able to modulate carbohydrate digestion and absorption in vitro as assessed by inhibition of α-amylase and maltase activities. The latter two compounds previously mistakenly identified as ferulic acid hexosides were purified and characterised and studied for their contribution to the overall bioactivity of chamomile. Molecular docking studies revealed that apigenin and cinnamic acids present totally different poses in the active site of human α-amylase. In differentiated Caco-2/TC7 cell monolayers, apigenin-7-O-glucoside and apigenin strongly inhibited D-[U-14C]-glucose and D-[U-14C]-sucrose transport, and less effectively D-[U-14C]-fructose transport. Inhibition of D-[U-14C]-glucose transport by apigenin was stronger under Na+-depleted conditions, suggesting interaction with the GLUT2 transporter. Competitive binding studies with molecular probes indicate apigenin interacts primarily at the exofacial-binding site of GLUT2. Taken together, the individual components of Chamomile are promising agents for regulating carbohydrate digestion and sugar absorption at the site of the gastrointestinal tract.
Pigmentation pattern and developmental constraints: flight muscle attachment sites delimit the thoracic trident of Drosophila melanogaster
Authors: Gibert Jean-Michel , Mouchel-Vielh Emmanuèle , Peronnet Frédérique
Published: March 2018

In their seminal paper published in 1979, Gould and Lewontin argued that some traits arise as by-products of the development of other structures and not for direct utility in themselves. We show here that this applies to the trident, a pigmentation pattern observed on the thorax of Drosophila melanogaster. Using reporter constructs, we show that the expression domain of several genes encoding pigmentation enzymes follows the trident shape. This domain is complementary to the expression pattern of stripe (sr), which encodes an essential transcription factor specifying flight muscle attachment sites. We demonstrate that sr limits the expression of these pigmentation enzyme genes to the trident by repressing them in its own expression domain, i.e. at the flight muscle attachment sites. We give evidence that repression of not only yellow but also other pigmentation genes, notably tan, is involved in the trident shape. The flight muscle attachment sites and sr expression patterns are remarkably conserved in dipterans reflecting the essential role of sr. Our data suggest that the trident is a by-product of flight muscle attachment site patterning that arose when sr was co-opted for the regulation of pigmentation enzyme coding genes.
Predicting affective valence using cortical hemodynamic signals
Authors: Trambaiolli Lucas R. , Biazoli Claudinei E. , Cravo André M. , Sato João R.
Published: March 2018

Ascribing affective valence to stimuli or mental states is a fundamental property of human experiences. Recent neuroimaging meta-analyses favor the workspace hypothesis for the neural underpinning of valence, in which both positive and negative values are encoded by overlapping networks but are associated with different patterns of activity. In the present study, we further explored this framework using functional near-infrared spectroscopy (fNIRS) in conjunction with multivariate analyses. We monitored the fronto-temporal and occipital hemodynamic activity of 49 participants during the viewing of affective images (passive condition) and during the imagination of affectively loaded states (active condition). Multivariate decoding techniques were applied to determine whether affective valence is encoded in the cortical areas assessed. Prediction accuracies of 89.90 ± 13.84% and 85.41 ± 14.43% were observed for positive versus neutral comparisons, and of 91.53 ± 13.04% and 81.54 ± 16.05% for negative versus neutral comparisons (passive/active conditions, respectively). Our results are consistent with previous studies using other neuroimaging modalities that support the affective workspace hypothesis and the notion that valence is instantiated by the same network, regardless of whether the affective experience is passively or actively elicited.
De novo draft assembly of the Botrylloides leachii genome provides further insight into tunicate evolution
Authors: Blanchoud Simon , Rutherford Kim , Zondag Lisa , Gemmell Neil J. , Wilson Megan J.
Published: March 2018

Tunicates are marine invertebrates that compose the closest phylogenetic group to the vertebrates. These chordates present a particularly diverse range of regenerative abilities and life-history strategies. Consequently, tunicates provide an extraordinary perspective into the emergence and diversity of these traits. Here we describe the genome sequencing, annotation and analysis of the Stolidobranchian Botrylloides leachii. We have produced a high-quality 159 Mb assembly, 82% of the predicted 194 Mb genome. Analysing genome size, gene number, repetitive elements, orthologs clustering and gene ontology terms show that B. leachii has a genomic architecture similar to that of most solitary tunicates, while other recently sequenced colonial ascidians have undergone genome expansion. In addition, ortholog clustering has identified groups of candidate genes for the study of colonialism and whole-body regeneration. By analysing the structure and composition of conserved gene linkages, we observed examples of cluster breaks and gene dispersions, suggesting that several lineage-specific genome rearrangements occurred during tunicate evolution. We also found lineage-specific gene gain and loss within conserved cell-signalling pathways. Such examples of genetic changes within conserved cell-signalling pathways commonly associated with regeneration and development that may underlie some of the diverse regenerative abilities observed in tunicates. Overall, these results provide a novel resource for the study of tunicates and of colonial ascidians.
Coherent changes of wintertime surface air temperatures over North Asia and North America
Authors: Yu Bin , Lin Hai
Published: March 2018

The surface temperature variance and its potential change with global warming are most prominent in winter over Northern Hemisphere mid-high latitudes. Consistent wintertime surface temperature variability has been observed over large areas in Eurasia and North America on a broad range of time scales. However, it remains a challenge to quantify where and how the coherent change of temperature anomalies occur over the two continents. Here we demonstrate the coherent change of wintertime surface temperature anomalies over North Asia and the central-eastern parts of North America for the period from 1951 to 2015. This is supported by the results from the empirical orthogonal function analysis of surface temperature and temperature trend anomalies over the Northern Hemisphere extratropical lands and the timeseries analysis of the regional averaged temperature anomalies over North Asia and the Great Plains and Great Lakes. The Asian-Bering-North American (ABNA) teleconnection provides a pathway to connect the regional temperature anomalies over the two continents. The ABNA is also responsible for the decadal variation of the temperature relationship between North Asia and North America.
Looking for variable molecular markers in the chestnut gall wasp Dryocosmus kuriphilus: first comparison across genes
Authors: Bonal Raúl , Vargas-Osuna Enrique , Mena Juan Diego , Aparicio José Miguel , Santoro María , Martín Angela
Published: March 2018

The quick spread of the chestnut gall wasp Dryocosmus kuriphilus in Europe constitutes an outstanding example of recent human-aided biological invasion with dramatic economic losses. We screened for the first time a set of five nuclear and mitochondrial genes from D. kuriphilus collected in the Iberian Peninsula, and compared the sequences with those available from the native and invasive range of the species. We found no genetic variability in Iberia in none of the five genes, moreover, the three genes compared with other European samples showed no variability either. We recorded four cytochrome b haplotypes in Europe; one was genuine mitochondrial DNA and the rest nuclear copies of mitDNA (numts), what stresses the need of careful in silico analyses. The numts formed a separate cluster in the gene tree and at least two of them might be orthologous, what suggests that the invasion might have started with more than one individual. Our results point at a low initial population size in Europe followed by a quick population growth. Future studies assessing the expansion of this pest should include a large number of sampling sites and use powerful nuclear markers (e. g. Single Nucleotide Polymorphisms) to detect genetic variability.
Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure
Authors: Yang Mu , Liu Yingye , Dai Jian , Li Lin , Ding Xin , Xu Zhe , Mori Masayuki , Miyahara Hiroki , Sawashita Jinko , Higuchi Keiichi
Published: March 2018

During acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2
−/−
) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR. AA amyloid deposition was suppressed in Apoa2
−/−
mice compared with wild type (WT) mice. During APR, Apoa2
−/−
mice exhibited significant suppression of serum SAA levels and hepatic Saa1 and Saa2 mRNA levels. Pathological investigation showed Apoa2
−/−
mice had less tissue damage and less inflammatory cell infiltration during APR. Total lipoproteins were markedly decreased in Apoa2
−/−
mice, while the ratio of HDL to low density lipoprotein (LDL) was also decreased. Both WT and Apoa2
−/−
mice showed increases in LDL and very large HDL during APR. SAA was distributed more widely in lipoprotein particles ranging from chylomicrons to very small HDL in Apoa2
−/−
mice. Our observations uncovered the critical roles of ApoA-II in inflammation, serum lipoprotein stability and AA amyloidosis morbidity, and prompt consideration of therapies for AA and other amyloidoses, whose precursor proteins are associated with circulating HDL particles.
Genome-wide analysis of dirigent gene family in pepper (Capsicum annuum L.) and characterization of CaDIR7 in biotic and abiotic stresses
Authors: Khan Abid , Li Ru-Jian , Sun Jian-Tian , Ma Fang , Zhang Huai-Xia , Jin Jing-Hao , Ali Muhammad , Haq Saeed ul , Wang Jun-E , Gong Zhen-Hui
Published: March 2018

The dirigent (DIR and DIR-like) proteins involved in lignification, play a pivotal role against biotic and abiotic stresses in plants. However, no information is available about DIR gene family in pepper (Capsicum annuum L.). In this study, 24 putative dirigent genes (CaDIRs) were identified, their gene structure, genome location, gene duplication and phylogenetic relationship were elucidated. Tissue-specific expression analysis displayed the highest transcription levels in flower, stem and leaf. Some CaDIRs were up-regulated by virulent (CaDIR2, 3, 6, 7, 11, 14, 16, 22 and 23) and avirulent (CaDIR3, 5, 7, 16, 20, 22, 23 and 24) Phytophthora capsici strains, as well as by Methyl jasmonate, salicylic acid, NaCl and mannitol stresses. Acid-soluble lignin content increased (103.21%) after P. capsici inoculation (48-hour). Silencing of CaDIR7 weakened plant defense by reducing (~50%) root activity and made plants more susceptible (35.7%) to P. capsici and NaCl (300 mM). Leaf discs of the CaDIR7:silenced plants exposed to NaCl and mannitol (300 mM each), exhibited a significant decrease (56.25% and 48% respectively) in the chlorophyll content. These results suggested that CaDIR7 is involved in pepper defense response against pathogen and abiotic stresses and the study will provide basic insights for future research regarding CaDIRs.
Real-time distribution of pelagic fish: combining hydroacoustics, GIS and spatial modelling at a fine spatial scale
Authors: Muška Milan , Tušer Michal , Frouzová Jaroslava , Mrkvička Tomáš , Ricard Daniel , Seďa Jaromír , Morelli Federico , Kubečka Jan
Published: March 2018

Understanding spatial distribution of organisms in heterogeneous environment remains one of the chief issues in ecology. Spatial organization of freshwater fish was investigated predominantly on large-scale, neglecting important local conditions and ecological processes. However, small-scale processes are of an essential importance for individual habitat preferences and hence structuring trophic cascades and species coexistence. In this work, we analysed the real-time spatial distribution of pelagic freshwater fish in the Římov Reservoir (Czechia) observed by hydroacoustics in relation to important environmental predictors during 48 hours at 3-h interval. Effect of diurnal cycle was revealed of highest significance in all spatial models with inverse trends between fish distribution and predictors in day and night in general. Our findings highlighted daytime pelagic fish distribution as highly aggregated, with general fish preferences for central, deep and highly illuminated areas, whereas nighttime distribution was more disperse and fish preferred nearshore steep sloped areas with higher depth. This turnover suggests prominent movements of significant part of fish assemblage between pelagic and nearshore areas on a diel basis. In conclusion, hydroacoustics, GIS and spatial modelling proved as valuable tool for predicting local fish distribution and elucidate its drivers, which has far reaching implications for understanding freshwater ecosystem functioning.
Virtual screening, Docking, ADMET and System Pharmacology studies on Garcinia caged Xanthone derivatives for Anticancer activity
Authors: Alam Sarfaraz , Khan Feroz
Published: March 2018

Caged xanthones are bioactive compounds mainly derived from the Garcinia genus. In this study, a structure-activity relationship (SAR) of caged xanthones and their derivatives for anticancer activity against different cancer cell lines such as A549, HepG2 and U251 were developed through quantitative (Q)-SAR modeling approach. The regression coefficient (r2), internal cross-validation regression coefficient (q2) and external cross-validation regression coefficient (pred_r2) of derived QSAR models were 0.87, 0.81 and 0.82, for A549, whereas, 0.87, 0.84 and 0.90, for HepG2, and 0.86, 0.83 and 0.83, for U251 respectively. These models were used to design and screened the potential caged xanthone derivatives. Further, the compounds were filtered through the rule of five, ADMET-risk and synthetic accessibility. Filtered compounds were then docked to identify the possible target binding pocket, to obtain a set of aligned ligand poses and to prioritize the predicted active compounds. The scrutinized compounds, as well as their metabolites, were evaluated for different pharmacokinetics parameters such as absorption, distribution, metabolism, excretion, and toxicity. Finally, the top hit compound 1G was analyzed by system pharmacology approaches such as gene ontology, metabolic networks, process networks, drug target network, signaling pathway maps as well as identification of off-target proteins that may cause adverse reactions.
Age is reflected in the Fractal Dimensionality of MRI Diffusion Based Tractography
Authors: Reishofer Gernot , Studencnik Fritz , Koschutnig Karl , Deutschmann Hannes , Ahammer Helmut , Wood Guilherme
Published: March 2018

Fractal analysis is a widely used tool to analyze the geometrical complexity of biological structures. The geometry of natural objects such as plants, clouds, cellular structures, blood vessel, and many others cannot be described sufficiently with Euclidian geometric properties, but can be represented by a parameter called the fractal dimension. Here we show that a specific estimate of fractal dimension, the correlation dimension, is able to describe changes in the structural complexity of the human brain, based on data from magnetic resonance diffusion imaging. White matter nerve fiber bundles, represented by tractograms, were analyzed with regards to geometrical complexity, using fractal geometry. The well-known age-related change of white matter tissue was used to verify changes by means of fractal dimension. Structural changes in the brain were successfully be observed and quantified by fractal dimension and compared with changes in fractional anisotropy.
The secretome from bovine mammosphere-derived cells (MDC) promotes angiogenesis, epithelial cell migration, and contains factors associated with defense and immunity
Authors: Ledet Melissa M. , Vasquez Amy K. , Rauner Gat , Bichoupan Allison A. , Moroni Paolo , Nydam Daryl V. , Van de Walle Gerlinde R.
Published: March 2018

Treatment of bovine mastitis with intramammary antibiotics is common, yet several concerns exist including failed efficacy for individual hosts or pathogens and the inability of approved drugs to revert mastitis-induced tissue damage to healthy tissue capable of returning to full milk production. These issues, in addition to aspects of public health such as accidental antibiotic residues in saleable milk and the potential for antimicrobial resistance, support the need to find alternative therapies for this costly disease. This study shows that the secretome, or collective factors, produced by mammosphere-derived cells (MDC) promotes angiogenesis, epithelial cell migration, and contains proteins associated with immunity and defense; all of which are necessary for healing damaged mammary gland tissue. Furthermore, we found that the MDC secretome remains effective after freezing and thawing, enhancing its therapeutic potential. Our results provide a foundation for further characterization of the individual secreted factors and the rationale for using the MDC secretome as a complementary treatment for bovine mastitis.
Using bivalve chronologies for quantifying environmental drivers in a semi-enclosed temperate sea
Authors: Peharda M. , Vilibić I. , Black B. A. , Markulin K. , Dunić N. , Džoić T. , Mihanović H. , Gačić M. , Puljas S. , Waldman R.
Published: March 2018

Annual growth increments formed in bivalve shells are increasingly used as proxies of environmental variability and change in marine ecosystems, especially at higher latitudes. Here, we document that well-replicated and exactly dated chronologies can also be developed to capture oceanographic processes in temperate and semi-enclosed seas, such as the Mediterranean. A chronology is constructed for Glycymeris pilosa from a shallow embayment of the northern Adriatic and extends from 1979 to 2016. The chronology significantly (p < 0.05) and positively correlates to winter sea surface temperatures, but negatively correlates to summer temperatures, which suggests that extreme winter lows and extreme summer highs may be limiting to growth. However, the strongest and most consistent relationships are negative correlations with an index of the Adriatic-Ionian Bimodal Oscillating System (BiOS) for which positive values indicate the inflow of the ultraoligotrophic Eastern Mediterranean waters to the Adriatic. In contrast, the substantial freshwater flows that discharge into the Adriatic do not correlate to the bivalve chronology, emphasizing the importance of remote oceanographic processes to growth at this highly coastal site. Overall, this study underscores the potential of bivalve chronologies to capture biologically relevant, local- to regional-scale patterns of ocean circulation in mid-latitude, temperate systems.
Global Proteomics Deciphered Novel-Function of Osthole Against Pulmonary Arterial Hypertension
Authors: Yao Li , Yang Yuxia , He Guanhong , Ou Chunqing , Wang Lan , Liu Kaixuan
Published: March 2018

Pulmonary arterial hypertension (PAH) is a progressive cardiovascular-disease with high mortality lacking high-efficiency drug. Our efforts attempted to delineate therapeutic action of osthole produced by Angelica Pubescens Maxim, which has the capacity to treat PAH by exploiting an iTRAQ-based proteomic method. Excitingly, osthole was observed to significantly restore 98 of 315 differential proteins significantly modified by PAH progression. They were primarily annotated into 24 signaling pathways. Four mostly affected proteins (RPL15, Cathepsin S, Histone H3.3 and HMGB1) were experimentially validated which belonged to ribosome pathway, oxidative phosphorylation pathway, systemic lupus erythematosus pathway, complement and coagulation cascades pathway, whose modifications and modulations mostly accounted for therapeutic capacity of this compound against PAH. Altogether, our findings demonstrated that global proteomics is a promising systems-biology approach for deciphering therapeutic actions and associated mechanisms of natural products derived from traditional Chinese medicine. Importantly, osthole is supposed to be a candidate compound for new drug development to treat PAH.
Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose
Authors: Laudenbach Megan , Baruffaldi Federico , Robinson Christine , Carter Philipp , Seelig Davis , Baehr Carly , Pravetoni Marco
Published: March 2018

Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation. Blockage of IL-4 signaling increased vaccine efficacy in blocking oxycodone distribution to the brain and protection against opioid-induced behavior and toxicity in mice. This strategy generalized to a peptide-protein conjugate immunogen, and a tetanus-diphtheria-pertussis vaccine. These data demonstrate that cytokine-based immunomodulators increase efficacy of vaccines against small molecules, peptides and proteins, and identify IL-4 as a pharmacological target for improving efficacy of next-generation vaccines.
Fathers’ eye colour sways daughters’ choice of both long- and short-term partners
Authors: Bressan Paola , Damian Valeria
Published: March 2018

In several species, mate choice is influenced by parental features through sexual imprinting, but in humans evidence is scarce and open to alternative explanations. We examined whether daughters’ preference for mates with light vs dark eyes is affected by the eye colour of parents. In an online study, over one thousand women rated the attractiveness of men as potential partners for either a long- or a short-term relationship. Each male face was shown twice, with light (blue or green) and with dark (brown or dark brown) eyes. Having a light-eyed father increased the preference for light-eyed men in both relationship contexts. Having light eyes increased this preference too, but only when men were regarded as potential long-term companions. Asymmetrically, in real life, father’s eye colour was the only predictor of partner’s eye colour; own colour was irrelevant. Mother’s eye colour never mattered, affecting neither preferences nor real-life choices. The effect of paternal eye colour was modulated by the quality of the relationship between father and daughter, suggesting (flexible) sexual imprinting rather than a simple inheritance of maternal preferences. Our data provide evidence that in humans, as in birds and sheep, visual experience of parental features shapes later sexual preferences.
In Vivo 3D Histomorphometry Quantifies Bone Apposition and Skeletal Progenitor Cell Differentiation
Authors: Yeh Shu-Chi A. , Wilk Katarzyna , Lin Charles P. , Intini Giuseppe
Published: March 2018

Histomorphometry and Micro-CT are commonly used to assess bone remodeling and bone microarchitecture. These approaches typically require separate cohorts of animals to analyze 3D morphological changes and involve time-consuming immunohistochemistry preparation. Intravital Microscopy (IVM) in combination with mouse genetics may represent an attractive option to obtain bone architectural measurements while performing longitudinal monitoring of dynamic cellular processesin vivo. In this study we utilized two-photon, multicolor fluorescence IVM together with a lineage tracing reporter mouse model to image skeletal stem cells (SSCs) in their calvarial suture niche and analyze their differentiation fate after stimulation with an agonist of the canonical Wnt pathway (recombinant Wnt3a). Ourin vivohistomorphometry analyses of bone formation, suture volume, and cellular dynamics showed that recombinant Wnt3a induces new bone formation, differentiation and incorporation of SSCs progeny into newly forming bone. IVM technology can therefore provide additional dynamic 3D information to the traditional static 2D histomorphometry.
Relation between colour- and phase changes of a leuco dye-based thermochromic composite
Authors: Bašnec Kristina , Perše Lidija Slemenik , Šumiga Boštjan , Huskić Miroslav , Meden Anton , Hladnik Aleš , Podgornik Bojana Boh , Gunde Marta Klanjšek
Published: March 2018

Reversible colour change of leuco dye-based composites is in general closely related to their phase change, thus the two phenomena should occur at around the same temperature and should be influenced similarly. However, spatial confinement of the analysed sample affects the change in colour differently compared to its phase transition and the most pronounced effects can be observed during cooling. The bulk composite is coloured while still liquid and the colour hysteresis does not exhibit a loop. In an open-porous medium the colouration coincides well with the crystallization and the colour hysteresis widens to about 4 °C. Microencapsulated composite exhibits two crystallization processes, one of them taking place at the bulk crystallization temperature and the other one at about 20 °C lower. Under such conditions the composite is coloured just before the onset of the second crystallization, i.e. about 15 °C below crystallization in the bulk, and the corresponding colour hysteresis widens to 18 °C. The two crystallization forms are thermally independent and have the same crystalline structure. These effects should be taken into account when designing future applications where the phase-changing materials are implemented.
Serum brain-derived neurotrophic factor predicting reduction in pulse pressure after a one-hour rest in nurses working night shifts
Authors: Lee I-Te , Sheu Wayne Huey-Herng , Lee Wen-Jane , Chen Der-Yuan
Published: March 2018

Night shift work is associated with cardiovascular disease and central nervous system disorders in female nurses. Brain-derived neurotrophic factor (BDNF) exerts protective effects on neural and endothelial functions. This study examined the association between serum BDNF levels and pulse pressure after rest in female nurses working night shifts. In this study, blood samples were collected for BDNF measurement after a night shift when nurses had been working night shifts for three continuous weeks. Blood pressure was assessed before and after a one-hour morning rest within a week of resuming the night shift after one month without any night shift work. The pulse pressure of nurses (n = 48, age 29 ± 5 years) was significantly reduced (from 43 ± 7 to 41 ± 6 mmHg, P = 0.003) after rest, and serum BDNF were significantly and inversely correlated with pulse pressure changes (r = −0.435, P = 0.002). Higher serum BDNF was an independent factor for greater reduction in pulse pressure (95%CI = −0.609 ‒ −0.174, P = 0.001). Using a receiver operating characteristic curve analysis, serum BDNF >20.6 ng/mL predicted a pulse pressure reduction after a one-hour rest (sensitivity 66.7%, specificity 77.8%). In conclusion, higher serum BDNF predicted greater recovery of pulse pressure after a one-hour rest in female nurses after night shift work.
An Inverse Optimal Control Approach to Explain Human Arm Reaching Control Based on Multiple Internal Models
Authors: Oguz Ozgur S. , Zhou Zhehua , Glasauer Stefan , Wollherr Dirk
Published: March 2018

Human motor control is highly efficient in generating accurate and appropriate motor behavior for a multitude of tasks. This paper examines how kinematic and dynamic properties of the musculoskeletal system are controlled to achieve such efficiency. Even though recent studies have shown that the human motor control relies on multiple models, how the central nervous system (CNS) controls this combination is not fully addressed. In this study, we utilize an Inverse Optimal Control (IOC) framework in order to find the combination of those internal models and how this combination changes for different reaching tasks. We conducted an experiment where participants executed a comprehensive set of free-space reaching motions. The results show that there is a trade-off between kinematics and dynamics based controllers depending on the reaching task. In addition, this trade-off depends on the initial and final arm configurations, which in turn affect the musculoskeletal load to be controlled. Given this insight, we further provide a discomfort metric to demonstrate its influence on the contribution of different inverse internal models. This formulation together with our analysis not only support the multiple internal models (MIMs) hypothesis but also suggest a hierarchical framework for the control of human reaching motions by the CNS.
Affinity maturation of humanized anti-epidermal growth factor receptor antibody using a modified phage-based open sandwich selection method
Authors: Sanada Hideaki , Kobayashi Kazuki , Oyama Kenji , Maru Takamitsu , Nakanishi Takeshi , Umetsu Mitsuo , Asano Ryutaro , Kumagai Izumi
Published: March 2018

Affinity maturation is one of the cardinal strategies for improving antibody function using in vitro evolutionary methods; one such well-established method is phage display. To minimise gene deletion, we previously developed an open sandwich (OS) method wherein selection was performed using only phage-displaying VH fragments after mixing with soluble VL fragments. The decrease in anti-EGFR antibody 528 affinity through humanization was successfully recovered by selecting VH mutants using this OS method. However, the affinity was not similar to that of parental 528. For further affinity maturation, we aimed to isolate VL mutants that act in synergy with VH mutants. However, the OS method could not be applied for selecting VL fragments because the preparation of soluble VH fragments was hampered by their instability and insolubility. Therefore, we initially designed a modified OS method based on domain-swapping of VH fragments, from added soluble Fv fragments to phage-displaying VL fragments. Using this novel Fv-added OS selection method, we successfully isolated VL mutants, and one of the Fv comprising VH and VL mutants showed affinity almost equivalent to that of parental 528. This method is applicable for engineering other VL fragments for affinity maturation.
Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region
Authors: Camargo Milena , Soto-De León Sara C. , Del Río-Ospina Luisa , Páez Astrid C. , González Zanony , González Edgardo , Cubides Juan R. , Camargo-Ayala Paola A. , Patarroyo Manuel E. , Patarroyo Manuel A.
Published: March 2018

Malaria outbreaks have been reported in recent years in the Colombian Amazon region, malaria has been re-emerging in areas where it was previously controlled. Information from malaria transmission networks and knowledge about the population characteristics influencing the dispersal of parasite species is limited. This study aimed to determine the distribution patterns ofPlasmodium vivax, P. malariaeandP. falciparumsingle and mixed infections, as well as the significant socio-spatial groupings relating to the appearance of such infections. An active search in 57 localities resulted in 2,106 symptomatic patients being enrolled. Parasitaemia levels were assessed by optical microscopy, and parasites were detected by PCR. The association between mixed infections (in 43.2% of the population) and socio-spatial factors was modelled using logistic regression and multiple correspondence analyses.P. vivaxoccurred most frequently (71.0%), followed byP. malariae(43.2%), in all localities. The results suggest that a parasite density-dependent regulation model (with fever playing a central role) was appropriate for modelling the frequency of mixed species infections in this population. This study highlights the under-reporting ofPlasmodiumspp. mixed infections in the malaria-endemic area of the Colombian Amazon region and the association between causative and environmental factors in such areas.
Genomic diversity in ochratoxigenic and non ochratoxigenic strains of Aspergillus carbonarius
Authors: Castellá Gemma , Bragulat M. Rosa , Puig Laura , Sanseverino Walter , Cabañes F. Javier
Published: March 2018

Ochratoxin A (OTA) is a mycotoxin with nephrotoxic effects on animals and humans.Aspergillus carbonariusis the main responsible for OTA contamination of grapes and derived products. We present the genome resequencing of fourA. carbonariusstrains, one OTA producer and three atypical and unique non-OTA producing strains. These strains were sequenced using Illumina technology and compared with a reference genome of this species. We performed some specific bioinformatics analyses in genes involved in OTA biosynthesis. Data obtained in this study revealed the high genomic diversity withinA. carbonariusstrains. Although some gaps of more than 1,000 bp were identified in non-ochratoxigenic strains, no large deletions in functional genes related with OTA production were found. Moreover, the expression of five genes of the putative OTA biosynthetic cluster was down regulated under OTA-inducing conditions in the non-ochratoxigenic strains. Knowledge of the regulatory mechanisms involved in OTA biosynthesis will provide a deeper understanding of these non-ochratoxigenic strains.
Genetic abrogation of immune checkpoints in antigen-specific cytotoxic T-lymphocyte as a potential alternative to blockade immunotherapy
Authors: Zhang Chi , Peng Yanchun , Hublitz Philip , Zhang Haokang , Dong Tao
Published: March 2018

T cell function can be compromised during chronic infections or through continuous exposure to tumor antigens by the action of immune checkpoint receptors, such as programmed cell death protein 1 (PD-1). Systemic administration of blocking antibodies against the PD-1 pathway can restore T cell function, and has been approved for the treatment of several malignancies, although there is a risk of adverse immune-related side-effects. We have developed a method for generating gene knockouts in human antigen (Ag)-specific cytotoxic T-Lymphocyte (CTLs) using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing. Using this method, we generated several transduced CD4+ or CD8+ antigen-specific polyclonal CTL lines and clones, and validated gene modifications of the PD-1 gene. We compared these T-cell lines and clones with control groups in the presence of programmed death-ligand 1 (PD-L1) and observed improved effector functions in the PD1-disrupted cell group. Overall, we have developed a versatile tool for functional genomics in human antigen-specific CTL studies. Furthermore, we provide an alternative strategy for current cell-based immunotherapy that will minimize the side effects caused by antibody blockade therapy.
Characterization of two novel mycoviruses from Penicillium digitatum and the related fungicide resistance analysis
Authors: Niu Yuhui , Yuan Yongze , Mao Jiali , Yang Zhu , Cao Qianwen , Zhang Tingfu , Wang Shengqiang , Liu Deli
Published: March 2018

Pathogenic fungi including Penicillium digitatum and Penicillium italicum are the main destructive pathogens in the citrus industry, causing great losses during postharvest process. To our knowledge, only one mycovirus from P. digitatum has been reported, and the prevalence of such mycoviruses against citrus postharvest pathogenic fungi and their genotyping were still under investigation. In the present study, we showed that 39 of 152 Penicillium isolates from main citrus-growing areas in China were infected with various mycoviruses belonging to polymycoviruses, Narna-like viruses, and families Totiviridae, Partitivirdae and Chrysoviridae. The next generation sequencing (NGS) towards virus genome library and the following molecular analysis revealed two novel mycoviruses Penicillium digitatum polymycovirus 1 (PdPmV1) and Penicillium digitatum Narna-like virus 1 (PdNLV1), coexisting in P. digitatum strain HS-RH2. The fungicide-resistant P. digitatum strains HS-F6 and HS-E9 coinfected by PdPmV1 and PdNLV1 exhibited obvious reduction in triazole drug prochloraz resistance by mycelial growth analysis on both PDA plates and citrus fruit epidermis with given prochloraz concentration. This report at the first time characterized two novel mycoviruses from P. digitatum and revealed the mycovirus-induced reduction of fungicide resistance.
Idelalisib impairs TREM-1 mediated neutrophil inflammatory responses
Authors: Alflen Astrid , Stadler Nicole , Aranda Lopez Pamela , Teschner Daniel , Theobald Matthias , Heß Georg , Radsak Markus P.
Published: March 2018

Triggering receptor expressed on myeloid cells (TREM)-1 on polymorphonuclear neutrophils (PMN) regulates innate immune activation in infectious and non-infectious conditions. TREM-1 ligation activates phosphatidyl-inositol 3 kinase (PI3K) triggering all neutrophil effector functions. As idelalisib is a PI3K inhibitor in clinical use for the treatment of non-Hodgkin lymphomas, we asked whether this inhibitor affects PMN functionalities. We analyzed PMNs from healthy donors or lymphoma patients for oxidative burst, phagocytosis, activation markers and IL-8 release upon TREM-1 or TLR ligation ex vivo. In addition, we performed western blot analyses to characterize the signaling events inhibited by idelalisib and other PI3K inhibitors. Upon TREM-1 ligation, the oxidative burst, degranulation, L-selectin shedding and cytokine release were all strongly reduced in the presence of idelalisib along impaired phosphorylation of P38, AKT and ERK by western blot analyses. In line with this, PMNs from patients receiving idelalisib also displayed an impaired TREM-1 mediated PMN activation ex vivo. In conclusion, PI3K inhibitors might cause a neutropenia-like susceptibility to infections in patients by leading to impaired PMN functionality. This should be considered when evaluating patients for infections treated with such inhibitors in daily clinical routine.
Targeted expression of step-function opsins in transgenic rats for optogenetic studies
Authors: Igarashi Hiroyuki , Ikeda Keiko , Onimaru Hiroshi , Kaneko Ryosuke , Koizumi Kyo , Beppu Kaoru , Nishizawa Kayo , Takahashi Yukari , Kato Fusao , Matsui Ko , Kobayashi Kazuto , Yanagawa Yuchio , Muramatsu Shin-Ichi , Ishizuka Toru , Yawo Hiromu
Published: March 2018

Rats are excellent animal models for experimental neuroscience. However, the application of optogenetics in rats has been hindered because of the limited number of established transgenic rat strains. To accomplish cell-type specific targeting of an optimized optogenetic molecular tool, we generated ROSA26/CAG-floxed STOP-ChRFR(C167A)-Venus BAC rats that conditionally express the step-function mutant channelrhodopsin ChRFR(C167A) under the control of extrinsic Cre recombinase. In primary cultured cortical neurons derived from this reporter rat, only Cre-positive cells expressing ChRFR(C167A) became bi-stable, that is, their excitability was enhanced by blue light and returned to the baseline by yellow~red light. In bigenic pups carrying the Phox2B-Cre driver, ChRFR(C167A) was specifically expressed in the rostral parafacial respiratory group (pFRG) in the medulla, where endogenous Phox2b immunoreactivity was detected. These neurons were sensitive to blue light with an increase in the firing frequency. Thus, this transgenic rat actuator/reporter system should facilitate optogenetic studies involving the effective in vivo manipulation of the activities of specific cell fractions using light of minimal intensity.
TAGLN2 polymerizes G-actin in a low ionic state but blocks Arp2/3-nucleated actin branching in physiological conditions
Authors: Kim Hye-Ran , Kwon Min-Sung , Lee Sangmin , Mun YeVin , Lee Kyung-Sik , Kim Chang-Hyun , Na Bo-Ra , Kim Bit Na Rae , Piragyte Indre , Lee Hyun-Su , Jun Youngsoo , Jin Mi Sun , Hyun Young-Min , Jung Hyun Suk , Mun Ji Young , Jun Chang-Duk
Published: March 2018

TAGLN is an actin-binding protein family that comprises three isoforms with theorized roles in smooth muscle differentiation, tumour development, lymphocyte activation, and brain chemistry. However, their fundamental characteristics in regulation of the actin-based cytoskeleton are not fully understood. Here we show that TAGLN2 (including TAGLN1 and TAGLN3) extensively nucleates G-actin polymerization under low-salt conditions, where polymerization would be completely suppressed. The calponin homology domain and actin-binding loop are essential to mechanically connect two adjacent G-actins, thereby mediating multimeric interactions. However, TAGLN2 blocked the Arp2/3 complex binding to actin filaments under physiological salt conditions, thereby inhibiting branched actin nucleation. In HeLa and T cells, TAGLN2 enhanced filopodium-like membrane protrusion. Collectively, the dual functional nature of TAGLN2—G-actin polymerization and Arp2/3 complex inhibition—may account for the mechanisms of filopodia development at the edge of Arp2/3-rich lamellipodia in various cell types.