bluuebunny/crossref_metadata_2025 huggingface dataset:
Mantle Zn Isotopic Heterogeneity Caused by Melt‐Rock Reaction: Evidence From Fe‐Rich Peridotites and Pyroxenites From the Bohemian Massif, Central Europe
Authors: Huang Jian , Ackerman Lukáš , Zhang Xing‐Chao , Huang Fang
Published: April 2019

To investigate the effect of melt‐rock reaction on Zn isotope fractionation and mantle Zn isotopic heterogeneity, we analyzed Zn isotopic compositions of peridotites, pyroxenites, and mineral separates from the Bohemian Massif, Central Europe. The Mg‐lherzolites (Mg# = 90.9 to 89.1, FeOT = 7.9 to 9.0 wt %) are melting residues with only moderate metasomatism and have δ66Zn from 0.11 to 0.20‰. In contrast, the Fe‐rich peridotites (Mg# = 88.2 to 80.3, FeOT = 10.0 to 14.5 wt %) and pyroxenites have larger ranges of δ66Zn from 0.11 to 0.31‰ and −0.33 to 0.42‰, respectively. Large disequilibrium intermineral Zn isotope fractionation occurs in the Fe‐rich peridotites and pyroxenites with Δ66ZnOpx‐Ol = −0.50‰, Δ66ZnGrt‐Ol = −0.55 to −0.39‰, Δ66ZnGrt‐Opx = −0.28 to −0.05‰, and Δ66ZnGrt‐Cpx = −0.50 to 0.12‰. Combined with their low SiO2 contents and radiogenic Sr‐Nd‐Os isotopic compositions, the high δ66Zn of the Fe‐rich peridotites is attributed to reaction between Mg‐lherzolites and percolating SiO2‐undersaturated basaltic melts that incorporated isotopically heavy crustal components. Crystallization of the isotopically heavy percolating melts migrating through the lithospheric mantle yield the high‐δ66Zn pyroxenites. The low δ66Zn of the pyroxenites and large intermineral Zn isotopic disequilibrium may result from kinetic Zn isotope fractionation during melt‐rock reaction. Collectively, these observations indicate that melt‐rock reaction can cause intermineral Zn isotopic disequilibrium and significant Zn isotopic heterogeneity in the mantle. This study thus highlights the potential use of Zn isotopes to trace melt‐rock reaction events in the mantle.
Senate Committee OK’s White House’s NOAA Pick in Party Line Vote
Authors: Showstack Randy
Published: April 2019

Senate floor fight may loom for Barry Lee Myers, whom Democrats oppose.
Defining the Limits of Greater India
Authors: Meng Jun , Gilder Stuart A. , Wang Chengshan , Coe Robert S. , Tan Xiaodong , Zhao Xixi , He Kuang
Published: April 2019

Greater India comprises a part of the Indian plate that subducted under Asia to help form the Tibetan Plateau. Defining the size of the Greater India is thus a key constraint to model the India‐Asia collision, growth of the plateau, and the tectonic evolution of the Neo‐Tethyan realm. We report Early Cretaceous paleomagnetic data from the central and eastern Tethyan Himalaya that yield paleolatitudes consistent with previous Early Cretaceous paleogeographic reconstructions. These data suggest Greater India extended at least 2,675 ± 720 and 1,950 ± 970 km farther north from the present northern margin of India at 83.6°E and 92.4°E, respectively. An area of lithosphere ≥4.7 × 106 km2 was consumed through subduction, thereby placing a strict limit on the minimum amount of Indian lithosphere consumed since the breakup of Gondwanaland.
The Relationship Between EMIC Wave Properties and Proton Distributions Based on Van Allen Probes Observations
Authors: Yue Chao , Jun Chae‐Woo , Bortnik Jacob , An Xin , Ma Qianli , Reeves Geoffrey D. , Spence Harlan E. , Gerrard Andrew J. , Gkioulidou Matina , Mitchell Donald G. , Kletzing Craig A.
Published: April 2019

Plasma kinetic theory predicts that sufficiently anisotropic proton distribution will excite electromagnetic ion cyclotron (EMIC) waves, which in turn relax the proton distribution to a marginally stable state creating an upper bound on the relaxed proton anisotropy. Here, using EMIC wave observations and coincident plasma measurements made by Van Allen Probes in the inner magnetosphere, we show that the proton distributions are well constrained by this instability to a marginally stable state. Near the threshold, the probability of EMIC wave occurrence is highest, having left‐handed polarization and observed near the magnetic equator with relatively small wave normal angles, indicating that these waves are locally generated. In addition, EMIC waves are distributed in two magnetic local time regions with different intensity. Compared with helium band waves, hydrogen band waves behave similarly except that they are often observed in low‐density regions. These results reveal several important features regarding EMIC waves excitation and propagation.
Temperature and soil moisture control microbial community composition in an arctic–alpine ecosystem along elevational and micro-topographic gradients
Authors: Frindte K , Pape R , Werner K , Löffler J , Knief C
Published: April 2019

Microbial communities in arctic–alpine soils show biogeographic patterns related to elevation, but the effect of fine-scale heterogeneity and possibly related temperature and soil moisture regimes remains unclear. We collected soil samples from different micro-topographic positions and elevational levels in two mountain regions of the Scandes, Central Norway. Microbial community composition was characterized by 16S rRNA gene amplicon sequencing and was dependent on micro-topography and elevation. Underlying environmental drivers were identified by integration of microbial community data with a comprehensive set of site-specific long-term recorded temperature and soil moisture data. Partial least square regression analysis allowed the description of ecological response patterns and the identification of the important environmental drivers for each taxonomic group. This demonstrated for the first time that taxa responding to elevation were indeed most strongly defined by temperature, rather than by other environmental factors. Micro-topography affected taxa were primarily controlled by temperature and soil moisture. In general, 5-year datasets had higher explanatory power than 1-year datasets, indicating that the microbial community composition is dependent on long-term developments of near-ground temperature and soil moisture regimes and possesses a certain resilience, which is in agreement with an often observed delayed response in global warming studies in arctic–alpine regions.
High proportions of bacteria are culturable across major biomes
Authors: Martiny Adam C
Published: April 2019

The paradigm that only 1% of microbes are culturable has had a profound impact on our understanding of microbial ecology and is still a major motivation for mostly using molecular tools to characterize microbial communities. However, this point is often expressed vaguely, suggesting that some scientists have different interpretations of the paradigm. In addition, there have been substantial advances in cultivation techniques suggesting that this paradigm may no longer be correct. To quantify bacterial culturability across six major biomes, I found that the median 16S rRNA similarity of bacteria to known cultured relatives was 97.3 ± 2.3% (s.d.). Furthermore, 52.0 ± 24% of sequences and 34.9 ± 23% of taxa (defined as >97% similar) had a closely related cultured relative. Thus, many cells and taxa across environments are culturable with known techniques, suggesting that the 1% paradigm is no longer correct.
Establishment of an induced memory response in Pseudomonas aeruginosa during infection of a eukaryotic host
Authors: Kordes Adrian , Grahl Nora , Koska Michal , Preusse Matthias , Arce-Rodriguez Alejandro , Abraham Wolf-Rainer , Kaever Volkhard , Häussler Susanne
Published: April 2019

In a given habitat, bacterial cells often experience recurrent exposures to the same environmental stimulus. The ability to memorize the past event and to adjust current behaviors can lead to efficient adaptation to the recurring stimulus. Here we demonstrate that the versatile bacterium Pseudomonas aeruginosa adopts a virulence phenotype after serial passage in the invertebrate model host Galleria mellonella. The virulence phenotype was not linked to the acquisition of genetic variations and was sustained for several generations, despite cultivation of the ex vivo virulence-adapted P. aeruginosa cells under rich medium conditions in vitro. Transcriptional reprogramming seemed to be induced by a host-specific food source, as reprogramming was also observed upon cultivation of P. aeruginosa in rich medium supplemented with polyunsaturated long-chain fatty acids. The establishment of induced memory responses adds a time dimension and seems to fill the gap between long-term evolutionary genotypic adaptation and short-term induced individual responses. Efforts to unravel the fundamental mechanisms that underlie the carry-over effect to induce such memory responses will continue to be of importance as hysteretic behavior can serve survival of bacterial populations in changing and challenging habitats.
Nrf2 signaling and autophagy are complementary in protecting lipopolysaccharide/d-galactosamine-induced acute liver injury by licochalcone A
Authors: Lv Hongming , Yang Huahong , Wang Zhongfeng , Feng Haihua , Deng Xuming , Cheng Genhong , Ci Xinxin
Published: April 2019

Licochalcone A (Lico A), isolated from Xinjiang licorice Glycyrrhiza inflate, has been shown to have antioxidative potential via the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) activation, which is involved in the prevention of acetaminophen-induced hepatotoxicity. The purpose of the current study was to further explore the protective effect of Lico A against lipopolysaccharide/d-galactosamine (LPS/GalN)-induced acute liver injury (ALI) and its underlying molecular mechanisms. Our results found that treatment with Lico A significantly reduced in LPS/GalN-induced hepatotoxicity by lessening lethality, alleviating histopathological liver changes, decreasing the alanine transaminase, and aspartate aminotransferase levels, attenuating the secretion of inflammatory cytokines, and regulating oxidative markers. Furthermore, Lico A efficiently alleviated LPS-induced inflammatory response by inhibiting TLR4-MAPK and -NF-κB, as well as the Txnip-NLRP3 signaling pathway. Meanwhile, Lico A induced the activation of Nrf2 and QSTM1 (P62) signaling and promoted autophagy involved in AMP-activated protein kinase (AMPK)-the transcription factor EB (TFEB) signaling, which may contribute to its hepatoprotective activity. Additional mechanistic investigations to evaluate the dependence of the hepatoprotective role of Lico A on Nrf2 revealed that a lack of Nrf2 promoted Lico A-induced autophagy, which contributed to the hepatoprotective effect of Lico A in Nrf2−/− mice. In addition, cotreatment with autophagy inhibitor (3-methyladenine, 3-MA) alleviated but did not abrogate the hepatoprotective effect of Lico A, which may be attributed to its ability to activate Nrf2. Our study firstly suggests that Lico A has protective potential against LPS/GalN-induced hepatotoxicity, which may be strongly associated with activation of Nrf2 and autophagy.
Di-n-butyl phthalate epigenetically induces reproductive toxicity via the PTEN/AKT pathway
Authors: Li Ran , Xing Qian-wei , Wu Xiao-lu , Zhang Lei , Tang Min , Tang Jing-yuan , Wang Jing-zi , Han Peng , Wang Shang-qian , Wang Wei , Zhang Wei , Zhou Guo-ping , Qin Zhi-qiang
Published: April 2019

Di-n-butyl phthalate (DBP) is a kind of ubiquitous chemical linked to hormonal disruptions that affects male reproductive system. However, the mechanism of DBP-induced germ cells toxicity remains unclear. Here, we demonstrate that DBP induces reduction of proliferation, increase of apoptosis and DNA damage dependent on the PTEN/AKT pathway. Mechanistically, DBP decreases PTEN promoter methylation and increases its transcriptional activity, leading to increased PTEN expression. Notably, DNMT3b is confirmed as a target of miR-29b and miR-29b-mediated status of PTEN methylation is involved in the effects of DBP treatment. Meanwhile, DBP decreases AKT pathway expression via increasing PTEN expression. In addition, the fact that DBP decreases the sperm number and the percentage of motile and progressive sperm is associated with downregulated AKT pathway and sperm flagellum-related genes. Collectively, these findings indicate that DBP induces aberrant PTEN demethylation, leading to inhibition of the AKT pathway, which contributes to the reproductive toxicity.
Asymmetric ephaptic inhibition between compartmentalized olfactory receptor neurons
Authors: Zhang Ye , Tsang Tin Ki , Bushong Eric A. , Chu Li-An , Chiang Ann-Shyn , Ellisman Mark H. , Reingruber Jürgen , Su Chih-Ying
Published: April 2019

In the Drosophila antenna, different subtypes of olfactory receptor neurons (ORNs) housed in the same sensory hair (sensillum) can inhibit each other non-synaptically. However, the mechanisms underlying this underexplored form of lateral inhibition remain unclear. Here we use recordings from pairs of sensilla impaled by the same tungsten electrode to demonstrate that direct electrical (“ephaptic”) interactions mediate lateral inhibition between ORNs. Intriguingly, within individual sensilla, we find that ephaptic lateral inhibition is asymmetric such that one ORN exerts greater influence onto its neighbor. Serial block-face scanning electron microscopy of genetically identified ORNs and circuit modeling indicate that asymmetric lateral inhibition reflects a surprisingly simple mechanism: the physically larger ORN in a pair corresponds to the dominant neuron in ephaptic interactions. Thus, morphometric differences between compartmentalized ORNs account for highly specialized inhibitory interactions that govern information processing at the earliest stages of olfactory coding.
Exceptional hydrogen storage achieved by screening nearly half a million metal-organic frameworks
Authors: Ahmed Alauddin , Seth Saona , Purewal Justin , Wong-Foy Antek G. , Veenstra Mike , Matzger Adam J. , Siegel Donald J.
Published: April 2019

Few hydrogen adsorbents balance high usable volumetric and gravimetric capacities. Although metal-organic frameworks (MOFs) have recently demonstrated progress in closing this gap, the large number of MOFs has hindered the identification of optimal materials. Here, a systematic assessment of published databases of real and hypothetical MOFs is presented. Nearly 500,000 compounds were screened computationally, and the most promising were assessed experimentally. Three MOFs with capacities surpassing that of IRMOF-20, the record-holder for balanced hydrogen capacity, are demonstrated: SNU-70, UMCM-9, and PCN-610/NU-100. Analysis of trends reveals the existence of a volumetric ceiling at ∼40 g H2 L−1. Surpassing this ceiling is proposed as a new capacity target for hydrogen adsorbents. Counter to earlier studies of total hydrogen uptake in MOFs, usable capacities in the highest-capacity materials are negatively correlated with density and volumetric surface area. Instead, capacity is maximized by increasing gravimetric surface area and porosity. This suggests that property/performance trends for total capacities may not translate to usable capacities.
Phenotypes associated with genes encoding drug targets are predictive of clinical trial side effects
Authors: Nguyen Phuong A. , Born David A. , Deaton Aimee M. , Nioi Paul , Ward Lucas D.
Published: April 2019

Only a small fraction of early drug programs progress to the market, due to safety and efficacy failures, despite extensive efforts to predict safety. Characterizing the effect of natural variation in the genes encoding drug targets should present a powerful approach to predict side effects arising from drugging particular proteins. In this retrospective analysis, we report a correlation between the organ systems affected by genetic variation in drug targets and the organ systems in which side effects are observed. Across 1819 drugs and 21 phenotype categories analyzed, drug side effects are more likely to occur in organ systems where there is genetic evidence of a link between the drug target and a phenotype involving that organ system, compared to when there is no such genetic evidence (30.0 vs 19.2%; OR = 1.80). This result suggests that human genetic data should be used to predict safety issues associated with drug targets.
A fungal substrate mimicking molecule suppresses plant immunity via an inter-kingdom conserved motif
Authors: Misas Villamil Johana C. , Mueller André N. , Demir Fatih , Meyer Ute , Ökmen Bilal , Schulze Hüynck Jan , Breuer Marlen , Dauben Helen , Win Joe , Huesgen Pitter F. , Doehlemann Gunther
Published: April 2019

Ustilago maydis is a biotrophic fungus causing corn smut disease in maize. The secreted effector protein Pit2 is an inhibitor of papain-like cysteine proteases (PLCPs) essential for virulence. Pit2 inhibitory function relies on a conserved 14 amino acids motif (PID14). Here we show that synthetic PID14 peptides act more efficiently as PLCP inhibitors than the full-length Pit2 effector. Mass spectrometry shows processing of Pit2 by maize PLCPs, which releases an inhibitory core motif from the PID14 sequence. Mutational analysis demonstrates that two conserved residues are essential for Pit2 function. We propose that the Pit2 effector functions as a substrate mimicking molecule: Pit2 is a suitable substrate for apoplastic PLCPs and its processing releases the embedded inhibitor peptide, which in turn blocks PLCPs to modulate host immunity. Remarkably, the PID14 core motif is present in several plant associated fungi and bacteria, indicating the existence of a conserved microbial inhibitor of proteases (cMIP).
Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour
Authors: Jones Samuel E. , van Hees Vincent T. , Mazzotti Diego R. , Marques-Vidal Pedro , Sabia Séverine , van der Spek Ashley , Dashti Hassan S. , Engmann Jorgen , Kocevska Desana , Tyrrell Jessica , Beaumont Robin N. , Hillsdon Melvyn , Ruth Katherine S. , Tuke Marcus A. , Yaghootkar Hanieh , Sharp Seth A. , Ji Yingjie , Harrison Jamie W. , Freathy Rachel M. , Murray Anna , Luik Annemarie I. , Amin Najaf , Lane Jacqueline M. , Saxena Richa , Rutter Martin K. , Tiemeier Henning , Kutalik Zoltán , Kumari Meena , Frayling Timothy M. , Weedon Michael N. , Gehrman Philip R. , Wood Andrew R.
Published: April 2019

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5 × 10−8, of which 20 reach a stricter threshold of P < 8 × 10−10. These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures.
Improved measures for evolutionary conservation that exploit taxonomy distances
Authors: Malhis Nawar , Jones Steven J. M. , Gsponer Jörg
Published: April 2019

Selective pressures on protein-coding regions that provide fitness advantages can lead to the regions' fixation and conservation in genome duplications and speciation events. Consequently, conservation analyses relying on sequence similarities are exploited by a myriad of applications across all biosciences to identify functionally important protein regions. While very potent, existing conservation measures based on multiple sequence alignments are so pervasive that improvements to solutions of many problems have become incremental. We introduce a new framework for evolutionary conservation with measures that exploit taxonomy distances across species. Results show that our taxonomy-based framework comfortably outperforms existing conservation measures in identifying deleterious variants observed in the human population, including variants located in non-abundant sequence domains such as intrinsically disordered regions. The predictive power of our approach emphasizes that the phenotypic effects of sequence variants can be taxonomy-level specific and thus, conservation needs to be interpreted accordingly.
Microphase separation of a miscible binary liquid mixture under confinement at the nanoscale
Authors: Essafri Ilham , Morineau Denis , Ghoufi Aziz
Published: April 2019

Recent experimental works suggested that the confinement into a cylindrical nanopore induced the microphase separation of a binary liquid, despite the miscible character of its bulk counterpart. A core–shell organization was evidenced such that one of the liquids was strongly anchored to the solid surface whereas the other was confined at the center of the pore. At the same time, a study based on atomistic simulations suggested a strong heterogeneity and the absence of a separation. In this work, by refining the solid–liquid interactions to qualitatively reproduce the experimental adsorption isotherms of both single liquids, the microphase separation and the core–shell structure are captured. By tuning the surface chemistry of the nanopore to mimic hydrophilic and hydrophobic confinement, we show that it is possible to control the structural characteristics of the core–shell structure.The molecular origin of the microphase separation is then ascribed to the strong hydrogen bonds and a commensurate arrangement between the confining material and both liquids.
Systematic review (protocol) of clinical effectiveness and models of care of low-resource pulmonary rehabilitation
Authors: Habib GM Monsur , Rabinovich Roberto , Divgi Kalyani , Ahmed Salahuddin , Saha Samir Kumar , Singh Sally , Uddin Aftab , Pinnock Hilary
Published: April 2019

More than half of the people with chronic respiratory diseases (CRDs) live in low- and middle-income countries (LMICs). The increasing disability, reduced productivity, associated anxiety and depression from CRDs result in social isolation and economic hardship for patients and their families. Pulmonary rehabilitation (PR) is a guideline-recommended multidisciplinary and multifaceted intervention that improves the physical and psychological condition of people with CRD. However, PR services are underprovided and uptake is poor in LMICs, especially in low-resourced setting. We aim to systematically assess the effectiveness, applicable components and mode of delivery of PR. We will search MEDLINE, EMBASE, CABI, AMED and CENTRAL from January 1990 using a PICOS search strategy (Population: adults with CRD (including chronic obstructive pulmonary disease, post-tuberculosis, remodelled asthma); Intervention: PR; Comparator: usual care; Outcomes: functional exercise capacity and Health-Related Quality-of-Life; Setting: low-resource settings). Two reviewers will independently screen titles/abstracts and full texts for eligibility and extract data from included papers. We will use the Cochrane Risk-of-Bias tool, rating the quality of evidence using GRADE. We will use narrative synthesis to answer our three objectives: What is the effectiveness of PR in low-resource settings? What components are used in effective studies? What models of service delivery are used? This systematic review will inform the potential impact and practical models of low-resource PR for the betterment of patients with CRDs to improve their substantial health-care burden and address poor quality of life.
Association of Circulating YKL-40 Levels and CHI3L1 Variants with the Risk of Spinal Deformity Progression in Adolescent Idiopathic Scoliosis
Authors: Nada Dina , Julien Cédric , Rompré Pierre H. , Akoume Marie-Yvonne , Gorman Kristen F. , Samuels Mark E. , Levy Emile , Kost Jason , Li Dawei , Moreau Alain
Published: April 2019

The cellular and molecular mechanisms underlying spinal deformity progression in adolescent idiopathic scoliosis (AIS) remain poorly understood. In this study, 804 French-Canadian patients and 278 age- and sex-matched controls were enrolled and genotyped for 12 single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene or its promoter. The plasma YKL-40 levels were determined by ELISA. We showed that elevation of circulating YKL-40 levels was correlated with a reduction of spinal deformity progression risk. We further identified significant associations of multiple CHI3L1 SNPs and their haplotypes with plasma YKL-40 levels and scoliosis severity as a function of their classification in a specific endophenotype. In the endophenotype FG3 group, we found that patients harboring the haplotype G-G-A-G-G-A (rs880633|rs1538372|rs4950881|rs10399805|rs6691378|rs946261), which presented in 48% of the cases, showed a positive correlation with the plasma YKL-40 levels (P = 7.6 × 10−6 and coefficient = 36). Conversely, the haplotype A-A-G-G-G-G, which presented in 15% of the analyzed subjects, showed a strong negative association with the plasma YKL-40 levels (P = 2 × 10−9 and coefficient = −9.56). We found that this haplotype showed the strongest association with AIS patients in endophenotype FG2 (P = 9.9 × 10−6 and coefficient = −13.53), who more often develop severe scoliosis compared to those classified in the other two endophenotypes. Of note, it showed stronger association in females (P = 1.6 × 10−7 and coefficient = −10.08) than males (P = 0.0021 and coefficient = −9.01). At the functional level, we showed that YKL-40 treatments rescued Gi-coupled receptor signalling dysfunction occurring in primary AIS osteoblasts. Collectively, our findings reveal a novel role for YKL-40 in AIS pathogenesis and a new molecular mechanism interfering with spinal deformity progression.
Mucosal and systemic SIV-specific cytotoxic CD4+ T cell hierarchy in protection following intranasal/intramuscular recombinant pox-viral vaccination of pigtail macaques
Authors: Khanna Mayank , Jackson Ronald J. , Alcantara Sheilajen , Amarasena Thakshila H. , Li Zheyi , Kelleher Anthony D. , Kent Stephen J. , Ranasinghe Charani
Published: April 2019

A HIV vaccine that provides mucosal immunity is urgently needed. We evaluated an intranasal recombinant Fowlpox virus (rFPV) priming vaccine followed by intramuscular Modified Vaccinia Ankara (rMVA) booster vaccine, both expressing SIV antigens. The vaccination generated mucosal and systemic SIV-specific CD4+ T cell mediated immunity and was associated with partial protection against high-dose intrarectal SIVmac251 challenge in outbred pigtail macaques. Three of 12 vaccinees were completely protected and these animals elicited sustained Gag-specific poly-functional, cytotoxic mucosal CD4+ T cells, complemented by systemic poly-functional CD4+ and CD8+ T cell immunity. Humoral immune responses, albeit absent in completely protected macaques, were associated with partial control of viremia in animals with relatively weaker mucosal/systemic T cell responses. Co-expression of an IL-4R antagonist by the rFPV vaccine further enhanced the breadth and cytotoxicity/poly-functionality of mucosal vaccine-specific CD4+ T cells. Moreover, a single FPV-gag/pol/env prime was able to induce rapid anamnestic gp140 antibody response upon SIV encounter. Collectively, our data indicated that nasal vaccination was effective at inducing robust cervico-vaginal and rectal immunity, although cytotoxic CD4+ T cell mediated mucosal and systemic immunity correlated strongly with ‘complete protection’, the different degrees of protection observed was multi-factorial.
Mapping Bromodomains in breast cancer and association with clinical outcome
Authors: Pérez-Pena Javier , Páez Raquel , Nieto-Jiménez Cristina , Sánchez Verónica Corrales , Galan-Moya Eva M. , Pandiella Atanasio , Győrffy Balázs , Ocana Alberto
Published: April 2019

A specific family of proteins that participate in epigenetic regulation is the bromodomain (BRD) family of proteins. In this work, we aimed to explore the expression of the BRD family at a transcriptomic level in breast cancer, and its association with patient survival. mRNA level data from normal breast and tumor tissues were extracted from public datasets. Gene set enrichment analysis (GSEA) was performed to identify relevant biological functions. The KM Plotter Online tool was used to evaluate the relationship between the presence of different genes and patient clinical outcome. mRNA level data from HER2+ breast cancer patients sensible and resistant to trastuzumab were also evaluated. The BRD family was an enriched function. In HER2 positive tumors the combined analyses of BRD2, BAZ1A, TRIM33 and ZMYND8 showed a detrimental relapse free survival (RFS). Similarly, the combined analysis of BRD2, BAZ1A, PHIP, TRIM33, KMT2A, ASH1L, PBRM1, correlated with an extremely poor overall survival (OS). The prognosis was confirmed using an independent dataset from TCGA. Finally, no relation between expression of BRD genes and response to trastuzumab was observed in the HER2 population. Upregulation of some BRD genes is associated with detrimental outcome in HER2 positive tumors, regardless trastuzumab treatment.
Utility Of POC Xpert HIV-1 Tests For Detection-Quantification Of Complex HIV Recombinants Using Dried Blood Spots From Kinshasa, D. R. Congo
Authors: Rubio-Garrido Marina , Ndarabu Adolphe , Reina Gabriel , Barquín David , Fernández-Alonso Mirian , Carlos Silvia , Holguín África
Published: April 2019

Point-of-Care (POC) molecular assays improve HIV infant diagnosis and viral load (VL) quantification in resource-limited settings. We evaluated POC performance in Kinshasa (Democratic Republic of Congo), with high diversity of HIV-1 recombinants. In 2016, 160 dried blood samples (DBS) were collected from 85 children (60 HIV−, 18 HIV+, 7 HIV-exposed) and 75 HIV+ adults (65 treated, 10 naive) at Monkole Hospital (Kinshasa). We compared viraemia with Cepheid-POC-Xpert-HIV-1VL and the non-POC-COBAS®AmpliPrep/COBAS®TaqMan®HIV-1-Testv2 in all HIV+, carrying 72.4%/7.2% HIV-1 unique/complex recombinant forms (URF/CRF). HIV-1 infection was confirmed in 14 HIV+ children by Cepheid-POC-Xpert-HIV-1Qual and in 70 HIV+ adults by both Xpert-VL and Roche-VL, identifying 8 false HIV+ diagnosis performed in DRC (4 adults, 4 children). HIV-1 was detected in 95.2% and 97.6% of 84 HIV+ samples by Xpert-VL and Roche-VL, respectively. Most (92.9%) HIV+ children presented detectable viraemia by both VL assays and 74.3% or 72.8% of 70 HIV+ adults by Xpert or Roche, respectively. Both VL assays presented high correlation (R2 = 0.89), but showing clinical relevant ≥0.5 log VL differences in 15.4% of 78 cases with VL within quantification range by both assays. This is the first study confirming the utility of Xpert HIV-1 tests for detection-quantification of complex recombinants currently circulating in Kinshasa.
The paradoxes of the Late Hesperian Mars ocean
Authors: Turbet M. , Forget F.
Published: April 2019

The long-standing debate on the existence of ancient oceans on Mars has been recently revived by evidence for tsunami resurfacing events that date from the Late Hesperian geological era. It has been argued that these tsunami events originated from the impact of large meteorites on a deglaciated or nearly deglaciated ocean present in the northern hemisphere of Mars. Here we show that the presence of such a late ocean faces a paradox. If cold, the ocean should have been entirely frozen shortly after its formation, thus preventing the formation of tsunami events. If warm, the ice-free ocean should have produced fluvial erosion of Hesperian Mars terrains much more extensively than previously reported. To solve this apparent paradox, we suggest a list of possible tests and scenarios that could help to reconcile constraints from climate models with tsunami hypothesis. These scenarios could be tested in future dedicated studies.
Tolerance of the freeze-dried mouse sperm nucleus to temperatures ranging from −196 °C to 150 °C
Authors: Wakayama Sayaka , Ito Daiyu , Kamada Yuko , Yonemura Shigenobu , Ooga Masatoshi , Kishigami Satoshi , Wakayama Teruhiko
Published: April 2019

It has long been believed that tolerance against extreme environments is possible only for ‘lower’ groups, such as archaea, bacteria or tardigrades, and not for more ‘advanced’ species. Here, we demonstrated that the mammalian sperm nucleus also exhibited strong tolerance to cold and hot temperatures. When mouse spermatozoa were freeze-dried (FD), similar to the anhydrobiosis of Tardigrades, all spermatozoa were ostensibly dead after rehydration. However, offspring were obtained from recovered FD sperm nuclei, even after repeated treatment with conditions from liquid nitrogen to room temperature. Conversely, when FD spermatozoa were heated at 95 °C, although the birth rate was decreased with increasing duration of the treatment, offspring were obtained even for FD spermatozoa that had been heat-treated for 2 h. This period was improved up to 6 h when glucose was replaced with trehalose in the freeze-drying medium, and the resistance temperature was extended up to 150 °C for short periods of treatment. Randomly selected offspring grew into healthy adults. Our results suggest that, when considering the sperm nucleus/DNA as the material that is used as a blueprint of life, rather than cell viability, a significant tolerance to extreme temperatures is present even in ‘higher’ species, such as mammals.
The human HOXA9 protein uses paralog-specific residues of the homeodomain to interact with TALE-class cofactors
Authors: Dard Amélie , Jia Yunlong , Reboulet Jonathan , Bleicher Françoise , Lavau Catherine , Merabet Samir
Published: April 2019

HOX proteins interact with PBX and MEIS cofactors, which belong to the TALE-class of homeodomain (HD)-containing transcription factors. Although the formation of HOX-PBX complexes depends on a unique conserved HOX motif called hexapeptide (HX), the additional presence of MEIS induces a remodeling of the interaction, leading to a global dispensability of the HX motif for trimeric complex formation in the large majority of HOX proteins. In addition, it was shown that the anterior HOXB3 and central HOXA7 and HOXC8 proteins could use different alternative TALE interaction motifs, with or without the HX motif, depending on the DNA-binding site and cell context. Here we dissected the molecular interaction properties of the human posterior HOXA9 protein with its TALE cofactors, PBX1 and MEIS1. Analysis was performed on different DNA-binding sites in vitro and by doing Bimolecular Fluorescence Complementation (BiFC) in different cell lines. Notably, we observed that the HOXA9-TALE interaction relies consistently on the redundant activity of the HX motif and two paralog-specific residues of the HOXA9 HD. Together with previous work, our results show that HOX proteins interact with their generic TALE cofactors through various modalities, ranging from unique and context-independent to versatile and context-dependent TALE binding interfaces.
Periocular skin warming elevates the distal skin temperature without affecting the proximal or core body temperature
Authors: Ichiba Tomohisa , Suzuki Masahiro , Aritake-Okada Sayaka , Uchiyama Makoto
Published: April 2019

Periocular skin warming reportedly improves the objective and subjective sleep quality in adults with mild difficulty in falling asleep. To clarify the effects of periocular warming, we examined the distal skin temperatures (hands and feet), proximal skin temperature (infraclavicular region) and core body temperature as well as the distal-proximal skin temperature gradient (DPG). Nineteen healthy males underwent two experimental sessions, wherein they used a warming or sham eye mask under a semi-constant routine protocol in a crossover manner. Participants were instructed to maintain wakefulness with their eyes closed for 60 minutes after wearing the eye mask. The warming eye mask increased the periocular skin temperature to 38–40 °C for the first 20 minutes, whereas the temperature remained unchanged with the sham mask. Compared to that of the sham eye mask, the warming eye mask significantly increased the temperatures of the hands and feet and the DPG, whereas the proximal skin and core body temperatures were unaffected. Subjective sleepiness and pleasantness were significantly increased by the warming eye mask. These results represent physiological heat loss associated with sleep initiation without affecting the proximal skin or core body temperatures, suggesting that thermal stimulation in certain areas can provoke similar changes in remote areas of the body.
O-GlcNAc Transferase Inhibition Differentially Affects Breast Cancer Subtypes
Authors: Barkovskaya Anna , Seip Kotryna , Hilmarsdottir Bylgja , Maelandsmo Gunhild M. , Moestue Siver A. , Itkonen Harri M.
Published: April 2019

Post-translational modification of intracellular proteins with a single N-acetylglucosamine sugar (O-GlcNAcylation) regulates signaling, proliferation, metabolism and protein stability. In breast cancer, expression of the enzyme that catalyzes O-GlcNAcylation – O-GlcNAc-transferase (OGT), and the extent of protein O-GlcNAcylation, are upregulated in tumor tissue, and correlate with cancer progression. Here we compare the significance of O-GlcNAcylation in a panel of breast cancer cells of different phenotypes. We find a greater dependency on OGT among triple-negative breast cancer (TNBC) cell lines, which respond to OGT inhibition by undergoing cell cycle arrest and apoptosis. Searching for the cause of this response, we evaluate the changes in the proteome that occur after OGT inhibition or knock-down, employing a reverse-phase protein array (RPPA). We identify transcriptional repressor - hairy and enhancer of split-1 (HES1) - as a mediator of the OGT inhibition response in the TNBC cells. Inhibition of OGT as well as the loss of HES1 results in potent cytotoxicity and apoptosis. The study raises a possibility of using OGT inhibition to potentiate DNA damage in the TNBC cells.
Effect of tolytoxin on tunneling nanotube formation and function
Authors: Dilsizoglu Senol Aysegul , Pepe Anna , Grudina Clara , Sassoon Nathalie , Reiko Ueoka , Bousset Luc , Melki Ronald , Piel Jörn , Gugger Muriel , Zurzolo Chiara
Published: April 2019

Tunneling nanotubes (TNTs) are actin-containing membrane protrusions that play an essential role in long-range intercellular communication. They are involved in development of various diseases by allowing transfer of pathogens or protein aggregates as well as organelles such as mitochondria. Increase in TNT formation has been linked to many pathological conditions. Here we show that nM concentrations of tolytoxin, a cyanobacterial macrolide that targets actin by inhibition of its polymerization, significantly decrease the number of TNT-connected cells, as well as transfer of mitochondria and α-synuclein fibrils in two different cell lines of neuronal (SH-SY5Y) and epithelial (SW13) origin. As the cytoskeleton of the tested cell remain preserved, this macrolide could serve as a valuable tool for future therapies against diseases propagated by TNTs.
Contrasting impacts of precipitation on Mediterranean birds and butterflies
Authors: Herrando Sergi , Titeux Nicolas , Brotons Lluís , Anton Marc , Ubach Andreu , Villero Dani , García-Barros Enrique , Munguira Miguel L. , Godinho Carlos , Stefanescu Constantí
Published: April 2019

The climatic preferences of the species determine to a large extent their response to climate change. Temperature preferences have been shown to play a key role in driving trends in animal populations. However, the relative importance of temperature and precipitation preferences is still poorly understood, particularly in systems where ecological processes are strongly constrained by the amount and timing of rainfall. In this study, we estimated the role played by temperature and precipitation preferences in determining population trends for birds and butterflies in a Mediterranean area. Trends were derived from long-term biodiversity monitoring data and temperature and precipitation preferences were estimated from species distribution data at three different geographical scales. We show that population trends were first and foremost related to precipitation preferences both in birds and in butterflies. Temperature preferences had a weaker effect on population trends, and were significant only in birds. The effect of precipitation on population trends operated in opposite directions in the two groups of species: butterfly species from arid environments and bird species from humid habitats are decreasing most. Our results indicate that, although commonly neglected, water availability is likely an important driver of animal population change in the Mediterranean region, with highly contrasting impacts among taxonomical groups.
Superlinear Photoluminescence by Ultrafast Laser Pulses in Dielectric Matrices with Metal Nanoclusters
Authors: Bornacelli J. , Torres-Torres C. , Silva-Pereyra H. G. , Labrada-Delgado G. J. , Crespo-Sosa A. , Cheang-Wong J. C. , Oliver A.
Published: April 2019

An intense photoluminescence emission was observed from noble metal nanoclusters (Pt, Ag or Au) embedded in sapphire plates, nucleated by MeV ion-implantation and assisted by an annealing process. In particular, the spectral photoluminescence characteristics, such as range and peak emission, were compared to the behavior observed from Pt nanoclusters embedded in a silica matrix and excited by UV irradiation. Correlation between emission energy, nanoclusters size and metal composition were analyzed by using the scaling energy relation EFermi/N1/3 from the spherical Jellium model. The metal nanocluster luminescent spectra were numerically simulated and correctly fitted using the bulk Fermi energy for each metal and a Gaussian nanoclusters size distribution for the samples. Our results suggest protoplasmonics photoluminescence from metal nanoclusters free of surface state or strain effects at the nanoclusters-matrix interface that can influence over their optical properties. These metal nanoclusters present very promising optical features such as bright visible photoluminescence and photostability under strong picosecond laser excitations. Besides superlinear photoluminescence from metal nanoclusters were also observed under UV high power excitation showing a quadratic dependence on the pump power fluence.
Pseudomonas aeruginosa inhibits Rhizopus microsporus germination through sequestration of free environmental iron
Authors: Kousser Courtney , Clark Callum , Sherrington Sarah , Voelz Kerstin , Hall Rebecca A.
Published: April 2019

Rhizopus spp are the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infection. Key to pathogenesis is the ability of fungal spores to swell, germinate, and penetrate surrounding tissues. Antibiotic treatment in at-risk patients increases the probability of the patient developing mucormycosis, suggesting that bacteria have the potential to control the growth of the fungus. However, research into polymicrobial relationships involving Rhizopus spp has not been extensively explored. Here we show that co-culturing Rhizopus microsporus and Pseudomonas aeruginosa results in the inhibition of spore germination. This inhibition was mediated via the secretion of bacterial siderophores, which induced iron stress on the fungus. Addition of P. aeruginosa siderophores to R. microsporus spores in the zebrafish larval model of infection resulted in inhibition of fungal germination and reduced host mortality. Therefore, during infection antibacterial treatment may relieve bacterial imposed nutrient restriction resulting in secondary fungal infections.
The Blue-Green Sensory Rhodopsin SRM from Haloarcula marismortui Attenuates Both Phototactic Responses Mediated by Sensory Rhodopsin I and II in Halobacterium salinarum
Authors: Chen Jheng-Liang , Lin Yu-Cheng , Fu Hsu-Yuan , Yang Chii-Shen
Published: April 2019

Haloarchaea utilize various microbial rhodopsins to harvest light energy or to mediate phototaxis in search of optimal environmental niches. To date, only the red light-sensing sensory rhodopsin I (SRI) and the blue light-sensing sensory rhodopsin II (SRII) have been shown to mediate positive and negative phototaxis, respectively. In this work, we demonstrated that a blue-green light-sensing (504 nm) sensory rhodopsin from Haloarcula marismortui, SRM, attenuated both positive and negative phototaxis through its sensing region. The H. marismortui genome encodes three sensory rhodopsins: SRI, SRII and SRM. Using spectroscopic assays, we first demonstrated the interaction between SRM and its cognate transducer, HtrM. We then transformed an SRM-HtrM fusion protein into Halobacterium salinarum, which contains only SRI and SRII, and observed that SRM-HtrM fusion protein decreased both positive and negative phototaxis of H. salinarum. Together, our results suggested a novel phototaxis signalling system in H. marismortui comprised of three sensory rhodopsins in which the phototactic response of SRI and SRII were attenuated by SRM.
The influence of the lack of insulin receptor substrate 2 (IRS2) on the thyroid gland
Authors: Iglesias-Osma Maria Carmen , Blanco Enrique J. , Carretero-Hernandez Marta , Catalano-Iniesta Leonardo , Sanchez-Robledo Virginia , Garcia-Barrado Maria Jose , Vicente-Garcia Teresa , Burks Deborah J. , Carretero Jose
Published: April 2019

Involvement of IRS2 in the proliferative effects of IGF-I of follicular thyroid cells has been described, but there are no evidences for in vivo participation of IRS2. This study aimed to analyse the in vivo relevance of IRS2 in the proliferation and apoptosis of thyroid cells by immunocytochemical studies for PCNA, Ki67, and active-caspase-3 in thyroid cells of IRS2 knockout (IRS2-KO) mice, jointly to TUNEL assay. Thyroid hormones were lower in IRS2-KO mice than in their wild-type (WT) counterparts. Increases in the area, perimeter and diameter of thyroid follicles of IRS2-KO mice were observed, which also showed increased proliferation rate of follicular cells and decreased percentage of apoptotic cells that was more evident in the central than in the marginal region of the gland. Sex-related differences were also found, since the follicular epithelium height was higher in male than in female mice. The percentage of proliferating cells showed significant changes in male but not in female mice, and apoptotic cells were more abundant in female than in male IRS2-KO animals, without significant differences between WT-animals. Therefore, our results suggest that IRS2 could be involved in the maintenance of thyroid cells population and in the normal physiology of the thyroid gland.
Polarimetry of photon echo on charged and neutral excitons in semiconductor quantum wells
Authors: Poltavtsev S. V. , Kapitonov Yu. V. , Yugova I. A. , Akimov I. A. , Yakovlev D. R. , Karczewski G. , Wiater M. , Wojtowicz T. , Bayer M.
Published: April 2019

Coherent optical spectroscopy such as four-wave mixing and photon echo generation deliver rich information on the energy levels involved in optical transitions through the analysis of polarization of the coherent response. In semiconductors, it can be applied to distinguish between different exciton complexes, which is a highly non-trivial problem in optical spectroscopy. We develop a simple approach based on photon echo polarimetry, in which polar plots of the photon echo amplitude are measured as function of the angle φ between the linear polarizations of the two exciting pulses. The rosette-like polar plots reveal a distinct difference between the neutral and charged exciton (trion) optical transitions in semiconductor nanostructures. We demonstrate this experimentally by photon echo polarimetry of a CdTe/(Cd, Mg)Te quantum well. The echoes of the trion and donor-bound exciton are linearly polarized at the angle 2φ with respect to the first pulse polarization and their amplitudes are weakly dependent on φ. While on the exciton the photon echo is co-polarized with the second exciting pulse and its amplitude scales as cosφ.