bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring biomolecule concentrations in tissue using a wearable droplet microfluidic-based sensor
Authors: Nightingale Adrian M. , Leong Chi Leng , Burnish Rachel A. , Hassan Sammer-ul , Zhang Yu , Clough Geraldine F. , Boutelle Martyn G. , Voegeli David , Niu Xize
Published: June 2019

Knowing how biomarker levels vary within biological fluids over time can produce valuable insight into tissue physiology and pathology, and could inform personalised clinical treatment. We describe here a wearable sensor for monitoring biomolecule levels that combines continuous fluid sampling with in situ analysis using wet-chemical assays (with the specific assay interchangeable depending on the target biomolecule). The microfluidic device employs a droplet flow regime to maximise the temporal response of the device, using a screw-driven push-pull peristaltic micropump to robustly produce nanolitre-sized droplets. The fully integrated sensor is contained within a small (palm-sized) footprint, is fully autonomous, and features high measurement frequency (a measurement every few seconds) meaning deviations from steady-state levels are quickly detected. We demonstrate how the sensor can track perturbed glucose and lactate levels in dermal tissue with results in close agreement with standard off-line analysis and consistent with changes in peripheral blood levels.
A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies
Authors: Happonen Lotta , Hauri Simon , Svensson Birkedal Gabriel , Karlsson Christofer , de Neergaard Therese , Khakzad Hamed , Nordenfelt Pontus , Wikström Mats , Wisniewska Magdalena , Björck Lars , Malmström Lars , Malmström Johan
Published: June 2019

A fundamental challenge in medical microbiology is to characterize the dynamic protein–protein interaction networks formed at the host–pathogen interface. Here, we generate a quantitative interaction map between the significant human pathogen,Streptococcus pyogenes, and proteins from human saliva and plasma obtained via complementary affinity-purification and bacterial-surface centered enrichment strategies and quantitative mass spectrometry. Perturbation of the network using immunoglobulin protease cleavage, mixtures of different concentrations of saliva and plasma, and differentS. pyogenesserotypes and their isogenic mutants, reveals how changing microenvironments alter the interconnectivity of the interaction map. The importance of host immunoglobulins for the interaction with human complement proteins is demonstrated and potential protective epitopes of importance for phagocytosis ofS. pyogenescells are localized. The interaction map confirms several previously described protein–protein interactions; however, it also reveals a multitude of additional interactions, with possible implications for host–pathogen interactions involving other bacterial species.
Lugdunin amplifies innate immune responses in the skin in synergy with host- and microbiota-derived factors
Authors: Bitschar Katharina , Sauer Birgit , Focken Jule , Dehmer Hanna , Moos Sonja , Konnerth Martin , Schilling Nadine A. , Grond Stephanie , Kalbacher Hubert , Kurschus Florian C. , Götz Friedrich , Krismer Bernhard , Peschel Andreas , Schittek Birgit
Published: June 2019

Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits Staphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-derived factors. We show that pretreatment of primary human keratinocytes or mouse skin with lugdunin in combination with microbiota-derived factors results in a significant reduction of S. aureus colonization. Moreover, lugdunin increases expression and release of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin, and results in the recruitment of monocytes and neutrophils in vivo, both by a TLR/MyD88-dependent mechanism. Interestingly, S. aureus elimination by lugdunin is additionally achieved by synergistic antimicrobial activity with LL-37 and dermcidin-derived peptides. In summary, our results indicate that lugdunin provides multi-level protection against S. aureus and may thus become a promising treatment option for S. aureus skin infections in the future.
Nonreciprocal charge transport at topological insulator/superconductor interface
Authors: Yasuda Kenji , Yasuda Hironori , Liang Tian , Yoshimi Ryutaro , Tsukazaki Atsushi , Takahashi Kei S. , Nagaosa Naoto , Kawasaki Masashi , Tokura Yoshinori
Published: June 2019

Topological superconductor is attracting growing interest for its potential application to topological quantum computation. The superconducting proximity effect on the topological insulator surface state is one promising way to yield topological superconductivity. The superconductivity realized at the interface between Bi2Te3 and non-superconductor FeTe is one such candidate. Here, to detect the mutual interaction between superconductivity and topological surface state, we investigate nonreciprocal transport; i.e., current-direction dependent resistance, which is sensitive to the broken inversion symmetry of the electronic state. The largely enhanced nonreciprocal phenomenon is detected in the Bi2Te3/FeTe heterostructure associated with the superconducting transition. The emergent nonreciprocal signal at low magnetic fields is attributed to the current-induced modulation of supercurrent density under the in-plane magnetic fields due to the spin-momentum locking. The angular dependence of the signal reveals the symmetry of superconductivity and indicates the existence of another mechanism of nonreciprocal transport at high fields.
Immature excitatory neurons develop during adolescence in the human amygdala
Authors: Sorrells Shawn F. , Paredes Mercedes F. , Velmeshev Dmitry , Herranz-Pérez Vicente , Sandoval Kadellyn , Mayer Simone , Chang Edward F. , Insausti Ricardo , Kriegstein Arnold R. , Rubenstein John L. , Manuel Garcia-Verdugo Jose , Huang Eric J. , Alvarez-Buylla Arturo
Published: June 2019

The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neurogenesis. Here we studied human PL development from embryonic stages to adulthood. The PL develops next to the caudal ganglionic eminence, which generates inhibitory interneurons, yet most PL neurons express excitatory markers. In children, most PL cells are immature (DCX+PSA-NCAM+), and during adolescence many transition into mature (TBR1+VGLUT2+) neurons. Immature PL neurons persist into old age, yet local progenitor proliferation sharply decreases in infants. Using single nuclei RNA sequencing, we identify the transcriptional profile of immature excitatory neurons in the human amygdala between 4–15 years. We conclude that the human PL contains excitatory neurons that remain immature for decades, a possible substrate for persistent plasticity at the interface of the hippocampus and amygdala.
Excitation of coherent second sound waves in a dense magnon gas
Authors: Tiberkevich V. , Borisenko I. V. , Nowik-Boltyk P. , Demidov V. E. , Rinkevich A. B. , Demokritov S. O. , Slavin A. N.
Published: June 2019

Second sound is a quantum mechanical effect manifesting itself as a wave-like (in contrast with diffusion) heat transfer, or energy propagation, in a gas of quasi-particles. So far, this phenomenon has been observed only in an equilibrium gas of phonons existing in liquid/solid helium, or in dielectric crystals (Bi, NaF) at low temperatures. Here, we report observation of a room-temperature magnonic second sound, or a wave-like transport of both energy and spin angular momentum, in a quasi-equilibrium gas of magnons undergoing Bose-Einstein condensation (BEC) in a ferrite film. Due to the contact of the magnon gas with pumping photons and phonons, dispersion of the magnonic second sound differ qualitatively from the phononic case, as there is no diffusion regime, and the second sound velocity remains finite at low wavenumbers. Formation of BEC in the gas of magnons modifies the second sound properties by creating an additional channel of energy relaxation.
RETRACTED ARTICLE: Pharmacokinetics, Biodistribution, and Anti-Angiogenesis Efficacy of Diamino Propane Tetraiodothyroacetic Acid-conjugated Biodegradable Polymeric Nanoparticle
Authors: Li Weikun , Yalcin Murat , Bharali Dhruba J. , Lin Qishan , Godugu Kavitha , Fujioka Kazutoshi , Keating Kelly A. , Mousa Shaker A.
Published: June 2019

The anti-angiogenic agent, diamino propane tetraiodothyroacetic acid (DAT), is a thyro-integrin (integrin αvβ3) antagonist anticancer agent that works via genetic and nongenetic actions. Tetraiodothyroacetic acid (tetrac) and DAT as thyroid hormone derivatives influence gene expression after they transport across cellular membranes. To restrict the action of DAT to the integrin αvβ3 receptors on the cell surface, we used DAT-conjugated PLGA nanoparticles (NDAT) in an active targeting mode to bind to these receptors. Preparation and characterization of NDAT is described, and both in vitro and in vivo experiments were done to compare DAT to NDAT. Intracellular uptake and distribution of DAT and NDAT in U87 glioblastoma cells were evaluated using confocal microscopy and showed that DAT reached the nucleus, but NDAT was restricted from the nucleus. Pharmacokinetic studies using LC-MS/MS analysis in male C57BL/6 mice showed that administration of NDAT improved the area under the drug concentration curve AUC(0–48 h) by 4-fold at a dose of 3 mg/kg when compared with DAT, and Cmax of NDAT (4363 ng/mL) was 8-fold greater than that of DAT (548 ng/mL). Biodistribution studies in the mice showed that the concentrations of NDAT were higher than DAT/Cremophor EL micelles in heart, lung, liver, spleen, and kidney. In another mouse model using female NCr nude homozygous mice with U87 xenografts, tumor growth was significantly decreased at doses of 1 and 3 mg/kg of NDAT. In the chick chorioallantoic membrane (CAM) assay used to measure angiogenesis, DAT (500 ng/CAM) resulted in 48% inhibition of angiogenesis levels. In comparison, NDAT at low dose (50 ng/CAM) showed 45% inhibition of angiogenesis levels. Our investigation of NDAT bridges the study of polymeric nanoparticles and anti-angiogenic agents and offers new insight for the rational design of anti-angiogenic agents.
Dosing and formulation of antenatal corticosteroids for fetal lung maturation and gene expression in rhesus macaques
Authors: Schmidt Augusto F. , Kannan Paranthaman S. , Bridges James P. , Filuta Alyssa , Lipps Dakota , Kemp Matthew , Miller Lisa A. , Kallapur Suhas G. , Xu Yan , Whitsett Jeffrey A. , Jobe Alan H.
Published: June 2019

Antenatal corticosteroids (ANS) are the major intervention to decrease respiratory distress syndrome and mortality from premature birth and are standard of care. The use of ANS is expanding to include new indications and gestational ages, although the recommended dosing was never optimized. The most widely used treatment is two intramuscular doses of a 1:1 mixture of betamethasone-phosphate (Beta-P) and betamethasone-acetate (Beta-Ac) – the clinical drug. We tested in a primate model the efficacy of the slow release Beta-Ac alone for enhancing fetal lung maturation and to reduce fetal corticosteroid exposure and potential toxic effects. Pregnant rhesus macaques at 127 days of gestation (80% of term) were treated with either the clinical drug (0.25 mg/kg) or Beta-Ac (0.125 mg/kg). Beta-Ac alone increased lung compliance and surfactant concentration in the fetal lung equivalently to the clinical drug. By transcriptome analyses the early suppression of genes associated with immune responses and developmental pathways were less affected by Beta-Ac than the clinical drug. Promoter and regulatory analysis prediction identified differentially expressed genes targeted by the glucocorticoid receptor in the lung. At 5 days the clinical drug suppressed genes associated with neuronal development and differentiation in the fetal hippocampus compared to control, while low dose Beta-Ac alone did not. A low dose ANS treatment with Beta-Ac should be assessed for efficacy in human trials.
Combined obeticholic acid and elafibranor treatment promotes additive liver histological improvements in a diet-induced ob/ob mouse model of biopsy-confirmed NASH
Authors: Roth Jonathan D. , Veidal Sanne S. , Fensholdt Louise K. D. , Rigbolt Kristoffer T. G. , Papazyan Romeo , Nielsen Jens Christian , Feigh Michael , Vrang Niels , Young Mark , Jelsing Jacob , Adorini Luciano , Hansen Henrik H.
Published: June 2019

Obeticholic acid (OCA) and elafibranor (ELA) are selective and potent agonists for the farnesoid X receptor (FXR) and dual peroxisome proliferator-activated receptor α/δ (PPAR-α/δ), respectively. Both agents have demonstrated clinical efficacy in nonalcoholic steatohepatitis (NASH). The present study used OCA and ELA to compare the effects of mono- and combination therapies on metabolic and histological endpoints in Lepob/ob mice with established diet-induced and biopsy-confirmed NASH (ob/ob-NASH). ob/ob-NASH mice were fed the AMLN diet high in trans-fat, fructose and cholesterol for 15 weeks, whereafter they received vehicle, OCA (30 mg/kg, PO, QD), ELA (3, 10 mg/kg, PO, QD), or combinations (OCA + ELA) for eight weeks. Within-subject comparisons were performed on histomorphometric changes, including fractional area of liver fat, galectin-3 and Col1a1. OCA and ELA monotherapies improved all quantitative histopathological parameters and OCA + ELA combinations exerted additive effects on metabolic and histological endpoints. In agreement with their different molecular mechanisms of action, OCA and ELA monotherapies elicited distinct hepatic gene expression profiles and their combination led to profound transcriptome changes associated with further improvements in lipid handling and insulin signaling, suppression of immune responses and reduced extracellular matrix formation. In conclusion, these findings provide preclinical proof-of-concept for combined FXR and PPAR-α/δ agonist-based therapies in NASH.
Role of hole confinement in the recombination properties of InGaN quantum structures
Authors: Anikeeva M. , Albrecht M. , Mahler F. , Tomm J. W. , Lymperakis L. , Chèze C. , Calarco R. , Neugebauer J. , Schulz T.
Published: June 2019

We study the isolated contribution of hole localization for well-known charge carrier recombination properties observed in conventional, polar InGaN quantum wells (QWs). This involves the interplay of charge carrier localization and non-radiative transitions, a non-exponential decay of the emission and a specific temperature dependence of the emission, denoted as “s-shape”. We investigate two dimensional In0.25Ga0.75N QWs of single monolayer (ML) thickness, stacked in a superlattice with GaN barriers of 6, 12, 25 and 50 MLs. Our results are based on scanning and high-resolution transmission electron microscopy (STEM and HR-TEM), continuous-wave (CW) and time-resolved photoluminescence (TRPL) measurements as well as density functional theory (DFT) calculations. We show that the recombination processes in our structures are not affected by polarization fields and electron localization. Nevertheless, we observe all the aforementioned recombination properties typically found in standard polar InGaN quantum wells. Via decreasing the GaN barrier width to 6 MLs and below, the localization of holes in our QWs is strongly reduced. This enhances the influence of non-radiative recombination, resulting in a decreased lifetime of the emission, a weaker spectral dependence of the decay time and a reduced s-shape of the emission peak. These findings suggest that single exponential decay observed in non-polar QWs might be related to an increasing influence of non-radiative transitions.
Different phenotypic plastic responses to predators observed among aphid lineages specialized on different host plants
Authors: Sentis Arnaud , Bertram Raphaël , Dardenne Nathalie , Ramon-Portugal Felipe , Louit Ines , Le Trionnaire Gaël , Simon Jean-Christophe , Magro Alexandra , Pujol Benoit , Hemptinne Jean-Louis , Danchin Etienne
Published: June 2019

The role of intraspecific variation in the magnitude and direction of plastic responses in ecology and evolution is increasingly recognized. However, the factors underlying intraspecific variation in plastic responses remain largely unexplored, particularly for the hypothesis that the herbivores’ phenotypic response to predators might vary amongst lineages associated with different host plants. Here, we tested whether plant-specialized lineages of the pea aphid, Acyrthosiphon pisum, differed in their transgenerational phenotypic response to ladybird predators (i.e., the asexual production of winged offspring by wingless mothers). In a full factorial laboratory experiment, we found that six aphid clonal lineages each specialized either on alfalfa or clover significantly differed in their transgenerational phenotypic response to predators. Some lineages produced an increased number of winged aphids in predator presence while others did not respond. Aphid lineages specialized on alfalfa had stronger phenotypic responses to predators than those specialized on clover. Although we tested only six aphid lineages from two biotypes, our results imply that intraspecific variation in prey phenotypic response of herbivores to predators differs amongst lineages specialized on different host plants. Our findings therefore raise the question of the influence of plant specialization in shaping herbivore phenotypic responses, and highlight the need to consider multi-trophic interactions to understand the causes and consequences of intraspecific variation in complex phenotypic traits.
Persistent effects of cyclic adenosine monophosphate are directly responsible for maintaining a neural network state
Authors: Perkins Matthew H. , Weiss Klaudiusz R. , Cropper Elizabeth C.
Published: June 2019

Network states are often determined by modulators that alter the synaptic and cellular properties of the constituent neurons. Frequently neuromodulators act via second messengers, consequently their effects can persist. This persistence at the cellular/molecular level determines the maintenance of the state at the network level. Here we study a feeding network in Aplysia. In this network, persistent modulation supports the maintenance of an ingestive state, biasing the network to generate ingestive motor programs. Neuropeptides that exert cyclic adenosine monophosphate (cAMP) dependent effects play an important role in inducing the ingestive state. Most commonly, modulatory effects exerted through cAMP signaling are persistent as a consequence of PKA activation. This is not the case in the neurons we study. Instead maintenance of the network state depends on the persistence of cAMP itself. Data strongly suggest that this is a consequence of the direct activation of a cyclic nucleotide gated current.
BioTarget: A Computational Framework Identifying Cancer Type Specific Transcriptional Targets of Immune Response Pathways
Authors: Hoang Tham H. , Zhao Yue , Lam Yiu , Piekos Stephanie , Han Yueh-Chiang , Reilly Cameron , Joshi Pujan , Hong Seung-Hyun , Sung Chang Ohk , Giardina Charles , Shin Dong-Guk
Published: June 2019

Transcriptome data can provide information on signaling pathways active in cancers, but new computational tools are needed to more accurately quantify pathway activity and identify tissue-specific pathway features. We developed a computational method called “BioTarget” that incorporates ChIP-seq data into cellular pathway analysis. This tool relates the expression of transcription factor TF target genes (based on ChIP-seq data) with the status of upstream signaling components for an accurate quantification of pathway activity. This analysis also reveals TF targets expressed in specific contexts/tissues. We applied BioTarget to assess the activity of TBX21 and GATA3 pathways in cancers. TBX21 and GATA3 are TF regulators that control the differentiation of T cells into Th1 and Th2 helper cells that mediate cell-based and humoral immune responses, respectively. Since tumor immune responses can impact cancer progression, the significance of our pathway scores should be revealed by effective patient stratification. We found that low Th1/Th2 activity ratios were associated with a significantly poorer survival of stomach and breast cancer patients, whereas an unbalanced Th1/Th2 response was correlated with poorer survival of colon cancer patients. Lung adenocarcinoma and lung squamous cell carcinoma patients had the lowest survival rates when both Th1 and Th2 responses were high. Our method also identified context-specific target genes for TBX21 and GATA3. Applying the BioTarget tool to BCL6, a TF associated with germinal center lymphocytes, we observed that patients with an active BCL6 pathway had significantly improved survival for breast, colon, and stomach cancer. Our findings support the effectiveness of the BioTarget tool for transcriptome analysis and point to interesting associations between some immune-response pathways and cancer progression.
Hyaluronan and LYVE-1 and allograft function in lung transplantation recipients
Authors: Courtwright Andrew M. , Lamattina Anthony M. , Louis Pierce H. , Trindade Anil J. , Burkett Patrick , Imani Jewel , Shrestha Shikshya , Divo Miguel , Keller Steve , Rosas Ivan O. , Goldberg Hilary J. , El-Chemaly Souheil
Published: June 2019

Hyaluronan (HA) is associated with innate immune response activation and may be a marker of allograft dysfunction in lung transplant recipients. This was a prospective, single center study comparing levels of bronchioalveolar lavage (BAL) and serum HA and the HA immobilizer LYVE-1 in lung transplant recipients with and without acute cellular rejection (ACR). Chronic lung allograft dysfunction (CLAD)-free survival was also evaluated based on HA and LYVE-1 levels. 78 recipients were enrolled with a total of 115 diagnostic biopsies and 1.5 years of median follow-up. Serum HA was correlated with BAL HA (r = 0.25, p = 0.01) and with serum LYVE-1 (r = 0.32, p = 0.002). There was significant variation in HA and LYVE-1 over time, regardless of ACR status. Levels of serum HA (median 74.7 vs 82.7, p = 0.69), BAL HA (median 149.4 vs 134.5, p = 0.39), and LYVE-1 (mean 190.2 vs 183.8, p = 0.72) were not associated with ACR. CLAD-free survival was not different in recipients with any episode of elevated serum HA (HR = 1.5, 95% CI = 0.3–7.7, p = 0.61) or BAL HA (HR = 0.94, 95% CI = 0.2–3.6, p = 0.93). These results did not differ when stratified by bilateral transplant status. In this small cohort, serum HA, BAL HA, and LYVE-1 levels are not associated with ACR or CLAD-free survival in lung transplant recipients.
Experimental and empirical evidence shows that reducing weed control in winter cereal fields is a viable strategy for farmers
Authors: Catarino Rui , Gaba Sabrina , Bretagnolle Vincent
Published: June 2019

Modern agriculture needs a paradigm shift to make the world’s food production sustainable while mitigating social and environmental externalities. Although various policies to limit the use of agrochemicals have recently been implemented in the European Union, the use of both herbicides and fertilizers has remained fairly constant. Farmers are assumed to behave optimally, producing the best they can, given the agronomic constraints of their fields. Based on this assumption, reducing agrochemicals should inevitably have negative effects on food production, or reduce farmers’ incomes. Coupling empirical analysis based on field surveys and experimental trials where weed management and nitrogen input were manipulated in the same production fields and under real farming conditions, we demonstrate that high use of N fertiliser or intense weed control slightly increase yields, but that this increase is not enough to offset the additional costs incurred by their use. Our experimental design allowed inputs to be varied in a two-factor design, along a gradient spanning from organic to highly intensive farming, while holding all other conditions constant and thus avoiding confounding effects. Quantification of crop yields and gross margins from winter cereal farming showed that reducing dependence on weed management may not hamper cereal production in this system, and is economically profitable at the field level on the short term. Our study thus contributes to addressing a key gap in our economic knowledge, and gives hope for implementing win-win strategies for farmers and the environment.
Sex ratios at birth vary with environmental harshness but not maternal condition
Authors: Schacht Ryan , Tharp Douglas , Smith Ken R.
Published: June 2019

The sex ratio at birth (SRB) may be patterned by maternal condition and/or environmental stressors. However, despite decades of research, empirical results from across the social and biological sciences are equivocal on this topic. Using longitudinal individual-level data from a US population during the interwar period (1918–1939), inclusive of three distinct eras (Spanish Flu, Roaring ‘20 s, and the Great Depression), we evaluate predictions from two theoretical frameworks used to study patterning in SRB – (1) ‘frail males’ and (2) adaptive sex-biased investment theory (Trivers-Willard). The first approach centers on greater male susceptibility to exogenous stressors and argues that offspring survival should be expected to differ between ‘good’ and ‘bad’ times. The second approach contends that mothers themselves play a direct role in manipulating offspring SRB, and that those in better condition should invest more in sons. In-line with ‘frail male’ predictions, we find that boys are less likely to be born during the environmentally challenging times of the Spanish Flu and Great Depression. However, we find no evidence that maternal condition is associated with sex ratios at birth, a result inconsistent with the Trivers-Willard hypothesis.
Genes functioned in kleptoplastids of Dinophysis are derived from haptophytes rather than from cryptophytes
Authors: Hongo Yuki , Yabuki Akinori , Fujikura Katsunori , Nagai Satoshi
Published: June 2019

Toxic dinoflagellates belonging to the genus Dinophysis acquire plastids indirectly from cryptophytes through the consumption of the ciliate Mesodinium rubrum. Dinophysis acuminata harbours three genes encoding plastid-related proteins, which are thought to have originated from fucoxanthin dinoflagellates, haptophytes and cryptophytes via lateral gene transfer (LGT). Here, we investigate the origin of these plastid proteins via RNA sequencing of species related to D. fortii. We identified 58 gene products involved in porphyrin, chlorophyll, isoprenoid and carotenoid biosyntheses as well as in photosynthesis. Phylogenetic analysis revealed that the genes associated with chlorophyll and carotenoid biosyntheses and photosynthesis originated from fucoxanthin dinoflagellates, haptophytes, chlorarachniophytes, cyanobacteria and cryptophytes. Furthermore, nine genes were laterally transferred from fucoxanthin dinoflagellates, whose plastids were derived from haptophytes. Notably, transcription levels of different plastid protein isoforms varied significantly. Based on these findings, we put forth a novel hypothesis regarding the evolution of Dinophysis plastids that ancestral Dinophysis species acquired plastids from haptophytes or fucoxanthin dinoflagellates, whereas LGT from cryptophytes occurred more recently. Therefore, the evolutionary convergence of genes following LGT may be unlikely in most cases.
Pharmacologic targeting of β-catenin improves fracture healing in old mice
Authors: Kwak Yoon Hae , Barrientos Tomasa , Furman Bridgette , Zhang Hazel , Puviindran Vijitha , Cutcliffe Hattie , Herfarth Jonas , Nwankwo Eugene , Alman Benjamin A.
Published: June 2019

β-catenin protein needs to be precisely regulated for effective fracture repair. The pace of fracture healing slows with age, associated with a transient increase in β-catenin during the initial phase of the repair process. Here we examined the ability of pharmacologic agents that target β-catenin to improve the quality of fracture repair in old mice. 20 month old mice were treated with Nefopam or the tankyrase inhibitor XAV939 after a tibia fracture. Fractures were examined 21 days later by micro-CT and histology, and 28 days later using mechanical testing. Daily treatment with Nefopam for three or seven days but not ten days improved the amount of bone present at the fracture site, inhibited β-catenin protein level, and increased colony forming units osteoblastic from bone marrow cells. At 28 days, treatment increased the work to fracture of the injured tibia. XAV939 had a more modest effect on β-catenin protein, colony forming units osteoblastic, and the amount of bone at the fracture site. This data supports the notion that high levels of β-catenin in the early phase of fracture healing in old animals slows osteogenesis, and suggests a pharmacologic approach that targets β-catenin to improve fracture repair in the elderly.
Supercontinuum generation by co-filamentation of two color femtosecond laser pulses
Authors: Vengris M. , Garejev N. , Tamošauskas G. , Čepėnas A. , Rimkus L. , Varanavičius A. , Jukna V. , Dubietis A.
Published: June 2019

In this paper, we experimentally investigate supercontinuum generation via collinear two-color filamentation in sapphire crystal, by launching two femtosecond pulses at fundamental (1030 nm) and second harmonic (515 nm) wavelengths from an amplified Yb:KGW laser. By changing the time delay between the incident pulses, we observe dramatic changes in the supercontinuum spectrum, transmitted energy, position of the nonlinear focus and intensity distribution along the filamentinduced luminescence traces. In particular, we show that at some delays the two pump wavelengths can assist each other in generating supercontinuum, whilst at other delays large portions of the supercontinuum spectrum are completely extinguished. The transition between supercontinuum generation and its extinction occurs within a very short (20 fs) span of the delay times, despite the fact that the pump pulses are 220 fs long. We propose that the observed non-trivial spectral dynamics can be interpreted by a mechanism, where co-propagating two pump pulses perturb the nonlinear refractive properties of the medium via Kerr effect and generation of free electron plasma thereby affecting pulse splitting and pulse front steepening, which are the key players in the process of supercontinuum generation in a normally dispersive medium.
Genetic markers of lipid metabolism genes associated with low susceptibility to HCV infection
Authors: Real Luis Miguel , Macías Juan , Rivero-Juárez Antonio , Téllez Francisco , Merino Dolores , Moreno-Grau Sonia , Orellana Adelina , Gómez-Salgado Juan , Sáez María E. , Frías Mario , Corma-Gómez Anaïs , Merchante Nicolás , Ruiz Agustín , Caruz Antonio , Pineda Juan A. ,   GEHEP 012 study group, Fernández-Fuertes Marta , Iglesias María , Rincón Pilar
Published: June 2019

Due to the relation between lipids and Hepatitis C virus (HCV) life-cycle, we aimed to explore the existence of single nucleotide polymorphisms (SNPs) associated with low susceptibility to HCV-infection within lipid metabolism genes. This was a case-control study in three phases: (I) allelic frequencies of 9 SNPs within 6 genes were compared in 404 HCV-infected patients and 801 population controls; (II) results were validated in 602 HCV-infected individuals and 1352 controls; (III) results were confirmed in 30 HCV-exposed uninfected (EU) individuals. In phase I, only the LDLRAP1-rs4075184-A allele was differentially distributed in patients and controls (358 of 808 alleles [44.3%] and 807 of 1602 alleles [50.3%], respectively) (p = 0.004). In phase II, the A allele frequency was 547 of 1204 alleles (45.4%) in patients and 1326 of 2704 alleles (49.0%) in controls (p = 0.037). This frequency in EU was 36 of 60 alleles (60%), which was higher than that observed in patients from phase I (p = 0.018) and phase II (p = 0.027). The LDLRAP1-mRNA expression was lower in AA carriers than in non-AA carriers (median [Q1-Q3]: 0.85 [0.17–1.75] relative-units [ru] versus 1.71 [1.00–2.73] ru; p = 0.041). Our results suggest that LDLRAP1-rs4075184-A allele is associated with lower susceptibility to HCV-infection and with reduced expression of LDLRAP1-mRNA.
Real time extended range prediction of heat waves over India
Authors: Mandal Raju , Joseph Susmitha , Sahai A. K. , Phani R. , Dey A. , Chattopadhyay R. , Pattanaik D. R.
Published: June 2019

Heat waves over India occur during the months of March-June. This study aims at the real-time monitoring and prediction of heat waves using a multi-model dynamical ensemble prediction system developed at Indian Institute of Tropical Meteorology, India. For this, a criterion has been proposed based on the observed daily gridded maximum temperature (Tmax) datasets, which can be used for real-time prediction as well. A heat wave day is identified when either (1) Tmax (a)≥ its climatological 95th percentile (calculated from daily values during March-June and for 1981–2010), (b) >36 °C, and (c) its departure from normal is >3.5 °C, Or, (2) when the Tmax >44 °C. Three heat wave prone regions, namely, northwest, southeast and northwest-southeast regions are recognized and heat wave spells of minimum consecutive six days are identified objectively for each region during 1981–2018. It is noticed that the prediction system has reasonable skill in predicting the heat waves over heat wave prone regions of India. Forecast verification of heat wave spells during 2003–2018 reveals that the prediction system has great potential in providing overall indication about the onset, duration and demise of the forthcoming heat wave spell with sufficient lead time albeit with some spatio-temporal error.
Electrification in granular gases leads to constrained fractal growth
Authors: Singh Chamkor , Mazza Marco G.
Published: June 2019

The empirical observation of aggregation of dielectric particles under the influence of electrostatic forces lies at the origin of the theory of electricity. The growth of clusters formed of small grains underpins a range of phenomena from the early stages of planetesimal formation to aerosols. However, the collective effects of Coulomb forces on the nonequilibrium dynamics and aggregation process in a granular gas – a model representative of the above physical processes – have so far evaded theoretical scrutiny. Here, we establish a hydrodynamic description of aggregating granular gases that exchange charges upon collisions and interact via the long-ranged Coulomb forces. We analytically derive the governing equations for the evolution of granular temperature, charge variance, and number density for homogeneous and quasi-monodisperse aggregation. We find that, once the aggregates are formed, the granular temperature of the cluster population, the charge variance of the cluster population and the number density of the cluster population evolve in such a way that their non-dimensional combination obeys a physical constraint of nearly constant dimensionless ratio of characteristic electrostatic to kinetic energy. This constraint on the collective evolution of charged clusters is confirmed both by  our theory and our detailed molecular dynamics simulations. The inhomogeneous aggregation of monomers and clusters in their mutual electrostatic field proceeds in a fractal manner. Our theoretical framework is extendable to more precise charge exchange mechanisms, a current focus of extensive experimentation. Furthermore, it illustrates the collective role of long-ranged interactions in dissipative gases and can lead to novel designing principles in particulate systems.
pH-dependent stability of honey bee (Apis mellifera) major royal jelly proteins
Authors: Mureşan Carmen I. , Buttstedt Anja
Published: June 2019

Honey bee larval food jelly is a secretion of the hypopharyngeal and mandibular glands of young worker bees that take care of the growing brood in the hive. Food jelly is fed to all larvae (workers, drones and queens) and as royal jelly to the queen bee for her entire life. Up to 18% of the food jelly account for proteins the majority of which belongs to the major royal jelly protein (MRJP) family. These proteins are produced in the hypopharyngeal glands at a pH value of 7.0. Before being fed to the larvae, they are mixed with the fatty acids secreted by the mandibular glands of the worker bees resulting at a pH of 4.0 in the food jelly. Thus, MRJPs are exposed to a broad pH range from their site of synthesis to the actual secreted larval food. We therefore determined the pH-dependent stability of MRJP1, MRJP2 and MRJP3 purified from royal jelly using differential scanning fluorimetry. All MRJPs were much more stable at acidic pH values compared to neutral ones with all proteins showing highest stability at pH 4.0 or 4.5, the native pH of royal jelly.
Deriving and validating biomarkers associated with autism spectrum disorders from a large-scale resting-state database
Authors: Chen Chia-Min , Yang Pinchen , Wu Ming-Ting , Chuang Tzu-Chao , Huang Teng-Yi
Published: June 2019

Resting-state functional magnetic resonance imaging (MRI) has been used to investigate the brain activity related to autism spectrum disorder (ASD). In this study, we applied information from a large-scale dataset, the Autism Brain Imaging Data Exchange (ABIDE), to clinical applications. We recruited 21 patients with ASD and 23 individuals with neurotypical development (TD). We applied ASD biomarkers derived from ABIDE datasets and subsequently investigated the relationship between the MRI biomarkers and indicators from clinical screening questionnaires, the social responsiveness scale (SRS), and the Swanson, Nolan, and Pelham Questionnaire IV. The results indicated that the biomarkers generated from the default mode and executive control networks significantly differed between the participants with ASD and TD. In particular, the biomarkers derived from the default mode network were negatively correlated with the raw scores and model factors of the SRS. In summary, this study transferred the efforts of the global autism research community to clinical applications and identified connectivity-based biomarkers in ASD.
YB-1 recruitment to stress granules in zebrafish cells reveals a differential adaptive response to stress
Authors: Guarino Andrea Maria , Mauro Giuseppe Di , Ruggiero Gennaro , Geyer Nathalie , Delicato Antonella , Foulkes Nicholas S. , Vallone Daniela , Calabrò Viola
Published: June 2019

The survival of cells exposed to adverse environmental conditions entails various alterations in cellular function including major changes in the transcriptome as well as a radical reprogramming of protein translation. While in mammals this process has been extensively studied, stress responses in non-mammalian vertebrates remain poorly understood. One of the key cellular responses to many different types of stressors is the transient generation of structures called stress granules (SGs). These represent cytoplasmic foci where untranslated mRNAs are sorted or processed for re-initiation, degradation, or packaging into mRNPs. Here, using the evolutionarily conserved Y-box binding protein 1 (YB-1) and G3BP1 as markers, we have studied the formation of stress granules in zebrafish (D. rerio) in response to different environmental stressors. We show that following heat shock, zebrafish cells, like mammalian cells, form stress granules which contain both YB-1 and G3BP1 proteins. Moreover, zfYB-1 knockdown compromises cell viability, as well as recruitment of G3BP1 into SGs, under heat shock conditions highlighting the essential role played by YB-1 in SG assembly and cell survival. However, zebrafish PAC2 cells do not assemble YB-1-positive stress granules upon oxidative stress induced by arsenite, copper or hydrogen peroxide treatment. This contrasts with the situation in human cells where SG formation is robustly induced by exposure to oxidative stressors. Thus, our findings point to fundamental differences in the mechanisms whereby mammalian and zebrafish cells respond to oxidative stress.
Topology Effects on Sparse Control of Complex Networks with Laplacian Dynamics
Authors: Constantino Pedro H. , Tang Wentao , Daoutidis Prodromos
Published: June 2019

Ease of control of complex networks has been assessed extensively in terms of structural controllability and observability, and minimum control energy criteria. Here we adopt a sparsity-promoting feedback control framework for undirected networks with Laplacian dynamics and distinct topological features. The control objective considered is to minimize the effect of disturbance signals, magnitude of control signals and cost of feedback channels. We show that depending on the cost of feedback channels, different complex network structures become the least expensive option to control. Specifically, increased cost of feedback channels favors organized topological complexity such as modularity and centralization. Thus, although sparse and heterogeneous undirected networks may require larger numbers of actuators and sensors for structural controllability, networks with Laplacian dynamics are shown to be easier to control when accounting for the cost of feedback channels.
Endothelial cells promote 3D invasion of GBM by IL-8-dependent induction of cancer stem cell properties
Authors: McCoy Michael G. , Nyanyo Dennis , Hung Carol K. , Goerger Julian Palacios , R. Zipfel Warren , Williams Rebecca M. , Nishimura Nozomi , Fischbach Claudia
Published: June 2019

Rapid growth and perivascular invasion are hallmarks of glioblastoma (GBM) that have been attributed to the presence of cancer stem-like cells (CSCs) and their association with the perivascular niche. However, the mechanisms by which the perivascular niche regulates GBM invasion and CSCs remain poorly understood due in part to a lack of relevant model systems. To simulate perivascular niche conditions and analyze consequential changes of GBM growth and invasion, patient-derived GBM spheroids were co-cultured with brain endothelial cells (ECs) in microfabricated collagen gels. Integrating these systems with 3D imaging and biochemical assays revealed that ECs increase GBM invasiveness and growth through interleukin-8 (IL-8)-mediated enrichment of CSCs. Blockade of IL-8 inhibited these effects in GBM-EC co-cultures, while IL-8 supplementation increased CSC-mediated growth and invasion in GBM-monocultures. Experiments in mice confirmed that ECs and IL-8 stimulate intracranial tumor growth and invasion in vivo. Collectively, perivascular niche conditions promote GBM growth and invasion by increasing CSC frequency, and IL-8 may be explored clinically to inhibit these interactions.
1 billion-year-old cell contents preserved in monazite and xenotime
Authors: Wacey David , Sirantoine Eva , Saunders Martin , Strother Paul
Published: June 2019

Exceptional microfossil preservation, whereby sub-cellular details of an organism are conserved, remains extremely rare in the Precambrian rock record. We here report the first occurrence of exceptional cellular preservation by the rare earth element (REE) phosphates monazite and xenotime. This occurs in ~1 billion-year-old lake sediments where REEs were likely concentrated by local erosion and drainage into a closed lacustrine basin. Monazite and xenotime preferentially occur inside planktonic cells where they preserve spheroidal masses of plasmolyzed cell contents, and occasionally also membranous fragments. They have not been observed associated with cell walls or sheaths, which are instead preserved by clay minerals or francolite. REE phosphates are interpreted to be the earliest minerals precipitated in these cells after death, with their loci controlled by the micro-scale availability of inorganic phosphate (Pi) and REEs, probably sourced from polyphosphate granules within the cells. The strong affinity of REEs for phosphate and the insolubility of these minerals once formed means that REE phosphates have the potential for rapid preservation of cellular morphology after death and durability in the rock record. Hence, authigenic REE phosphates provide a promising new target in the search for the preservation of intra-cellular components of fossilised microorganisms.
Relationship between serum uric acid and hypertension: a cross-sectional study in Bangladeshi adults
Authors: Ali Nurshad , Mahmood Shakil , Islam Farjana , Rahman Shahnaz , Haque Tangigul , Islam Shiful , Rahman Sadaqur , Haque Nazmul , Mosaib Golam , Perveen Rasheda , Khanum Farida Adib
Published: June 2019

Experimental evidence suggests a causal role of serum uric acid (SUA) in hypertension development. Currently, there are few data available on the association between SUA and hypertension; data from Bangladeshi adults are not available yet. This study evaluated the association of SUA with hypertension among Bangladeshi adults. Blood samples were obtained from 140 males and 115 females and analyzed for SUA and lipid levels. Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg. All participants were divided into four quartiles based on SUA concentrations. Association of SUA with hypertension was evaluated by logistic regression models. The prevalence of hypertension and prehypertension was significantly higher in male (15.4 and 47.6%, respectively) than in the female (5.6 and 33.4%, respectively) subjects (p < 0.01). Males had a higher mean level of SUA (310.7 ± 67.9 µmol/L) than in the females (255.3 ± 69.3 µmol/L) (p < 0.001). Hyperuricemia was prevalent 9.1% in males and 10.3% in females. An increasing trend for hypertension and prehypertension was found in both genders with increasing SUA levels in the quartiles (p < 0.01). SUA levels in the quartiles were positively correlated with blood pressure (p < 0.01). After adjusting for baseline covariates, SUA levels were significantly associated with hypertension (p < 0.01). Findings of this study indicate the significance of maintaining normal SUA level to prevent hypertension.
Quantum reflection above the classical radiation-reaction barrier in the quantum electro-dynamics regime
Authors: Geng X. S. , Ji L. L. , Shen B. F. , Feng B. , Guo Z. , Yu Q. , Zhang L. G. , Xu Z. Z.
Published: June 2019

High brightness gamma rays can be generated by colliding an ultra-intense laser pulse with a high energy electron beam. This collision phenomenon also represents a powerful approach to explore new physics in the exotic strong field Quantum Electro-Dynamics (QED) regime. Here we show that in the cross-collision geometry, there exists a barrier induced by the classical radiation-reaction force that prohibits electrons of arbitrarily high energies to pass. However, such classical barrier vanishes in the QED picture, where electrons can be well reflected (transmitted) in the regimes forbidden by classical theory. This effect can be measured in the up-coming 10–100 PW laser facilities for laser intensities at 2 × 1023 W cm−2 and electron energies of ~102 MeV. The results are capable of identifying the boundaries between classical and QED approaches in the strong field regime and confirming the various models describing this fundamental process.
Determination of formaldehyde in cosmetic products using gas-diffusion microextraction coupled with a smartphone reader
Authors: Lamarca Rafaela Silva , Luchiari Natalia da Costa , Bonjorno Andressa Francielli , Passaretti Filho Juliano , Cardoso Arnaldo Alves , Lima Gomes Paulo Clairmont Feitosa de
Published: June 2019

A GDME extraction followed by smartphone image acquisition permitted fast, reduced reagent, waste generation and low cost method to determine formaldehyde in cosmetic samples.
Double stranded DNA-templated copper nanoclusters as a novel fluorescent probe for label-free detection of rutin
Authors: Lai Yanqiong , Teng Xia , Zhang Yanli , Wang Hongbin , Pang Pengfei , Yang Chun , Barrow Colin J. , Yang Wenrong
Published: June 2019

In this study, we developed a simple, sensitive, low-cost and label-free method to detect rutin by using double-stranded DNA-templated copper nanoclusters (dsDNA-CuNCs) as a fluorescent probe.