bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive credible intervals on stratigraphic ranges when recovery potential is unknown
Authors: Wang Steve C. , Everson Philip J. , Zhou Heather Jianan , Park Dasol , Chudzicki David J.
Published: February 2016

Numerous methods exist for estimating the true stratigraphic range of a fossil taxon based on the stratigraphic positions of its fossil occurrences. Many of these methods require the assumption of uniform fossil recovery potential—that fossils are equally likely to be found at any point within the taxon's true range. This assumption is unrealistic, because factors such as stratigraphic architecture, sampling effort, and the taxon's abundance and geographic range affect recovery potential. Other methods do not make this assumption, but they instead require a priori quantitative knowledge of recovery potential that may be difficult to obtain. We present a new Bayesian method, the Adaptive Beta method, for estimating the true stratigraphic range of a taxon that works for both uniform and non-uniform recovery potential. In contrast to existing methods, we explicitly estimate recovery potential from the positions of the occurrences themselves, so that a priori knowledge of recovery potential is not required. Using simulated datasets, we compare the performance of our method with existing methods. We show that the Adaptive Beta method performs well in that it achieves or nearly achieves nominal coverage probabilities and provides reasonable point estimates of the true extinction in a variety of situations. We demonstrate the method using a dataset of the Cambrian molluscAnabarella.
Epitope mapping ofBrugia malayiALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis
Authors: Madhumathi J. , Prince P.R. , Rao D.N. , Karande A.A. , Reddy M.V.R. , Kaliraj P.
Published: February 2016

Human lymphatic filariasis is a neglected tropical disease, causing permanent and long-term disability with severe immunopathology. Abundant larval transcript (ALT) plays a crucial role in parasite establishment in the host, due to its multi-faceted ability in host immune regulation. Although ALT protein is a key filarial target, its exact function is yet to be explored. Here, we report epitope mapping and a structural model ofBrugia malayiALT-2, leading to development of a multi-epitope vaccine. Structural analysis revealed that ALT represents unique parasitic defence proteins belonging to a toxin family that carries a ‘knottin’ fold. ALT-2 has been a favourite vaccine antigen and was protective in filarial models. Due to the immunological significance of ALT-2, we mapped B-cell epitopes systematically and identified two epitope clusters, 1–30 and 89–128. To explore the prophylactic potential of epitope clusters, a recombinant multi-epitopic gene comprising the epitopic domains was engineered and the protective efficacy of recombinant ALT epitope protein (AEP) was tested in the permissive model,Mastomys coucha. AEP elicited potent antibody responses with predominant IgG1 isotype and conferred significantly high protection (74.59%) compared to ALT-2 (61.95%). This proved that these epitopic domains are responsible for the protective efficacy of ALT-2 and engineering protective epitopes as a multi-epitope protein may be a novel vaccine strategy for complex parasitic infections.
Type studies in theRhizocarpon geographicumgroup (Rhizocarpaceae, lichenized Ascomycota)
Authors: ROCA-VALIENTE Beatriz , HAWKSWORTH David L. , PÉREZ-ORTEGA Sergio , SANCHO Leopoldo G. , CRESPO Ana
Published: February 2016

As part of a comprehensive revision of theRhizocarpon geographicumspecies group using molecular and morphological approaches, we examined the name-bearing types of 15 species. We report ambiguities and inconsistencies with the reported features of some type specimens, original descriptions, and circumscriptions employed in keys for the identification of taxa within the complex. The reporting of chemical reactions and some morphological characters was found to be inconsistent and likely to lead to errors of identification. This is unfortunate in view of the widespread use of the complex in glaciology for lichenometry. Issues surrounding the typification of the basionymLichen geographicusare clarified, and the epitype is illustrated. The complex nomenclatural situation regarding the nameRhizocarpon lecanorinumand its typification is also made clear. The examination of the anatomical and morphological characters presented here needs to be considered together with molecular phylogenetic information to provide a more informed new taxonomy of the group.
Three new species ofAtlafrom calcareous rocks (Verrucariaceae, lichenized Ascomycota)
Authors: PYKÄLÄ Juha , MYLLYS Leena
Published: February 2016

Three new species ofAtlaare described from calcareous rocks in northern Finland based on morphology and ITS sequences. All new species have dark brown spores but have smaller perithecia and spores than previously known brown-spored species ofAtla.Atla tibelliorumsp. nov. resemblesSporodictyon arcticum, but has a dark brown exciple and larger spores.Atla oulankaensissp. nov. andA. vitikaineniisp. nov. differ fromA. alpinain the smaller perithecia and spores. Atla vitikaineniihas an involucrellum often slightly diverging from the exciple.Atla oulankaensisis similar toA. vitikainenii, differing in slightly narrower spores and in having some involucrella incurving under the exciple or even enveloping the exciple. An unidentified ITS sequence from Canada obtained from GenBank most probably belongs toA. oulankaensisand another unidentified sequence from the USA toA. tibelliorum. The new results strengthen the conclusion that the genera ofAtlaandSporodictyoncannot be separated by morphology alone. A key to all known species ofAtlaandSporodictyonis provided.
The genusBulbothrix(Parmeliaceae) in China
Authors: ZHANG Yan Yun , WANG Xin Yu , LIU Dong , SHI Hai Xia , YE Xin , YANG Mei Xia , WANG Li Song
Published: February 2016

The morphology, chemistry and phylogenetic relationships of Chinese populations ofBulbothrixare described. Nine species, including two new speciesB. mammillariaY. Y. Zhang & Li S. Wang sp. nov. andB. laciniaY. Y. Zhang & Li S. Wang sp. nov., and two newly recorded for the flora,B. scortellaandB. meizospora, are reported.Bulbothrix mammillariacan be recognized by the sparse cilia that are reduced to a bulbate structure and the broad lobes (3–11 mm).Bulbothrix laciniadiffers from other species of the genus by dark brown, spherical to short-cylindrical isidia and common lacinulae on the upper surface. Phylogenetic relationships of currently known ITS sequences fromBulbothrixwere inferred to assess the affinities of the new species. A key to all known species from China is presented.
John Stuart Mill and the Contagious Diseases Acts: Whose Law? Whose Liberty? Whose Greater Good?’
Authors: Jose Jim , McLoughlin Kcasey
Published: February 2016

Legal fictions are often used to lubricate the machinery of jurisprudence. One of these is the idea that laws created to restrict the liberty of some individuals or class of individuals in order to protect the public good are in effect outcomes of tradeoffs between abstract universals, namely liberty and the public good. A three way relationship is imagined in which law, liberty, and the public good are in creative tension. The role of the law in this three way tension is further imagined to be the mediator where it serves to calibrate this tension in ways that are also assumed to legitimate the intended outcomes in practice. In particular, where the outcome is the prevention of harm, then laws that curtail liberty must be seen not just as measures for the public good, but rather as necessitated by the potential effects of the very harm itself. The justification for this view is often traced back to the views of nineteenth century political philosopher John Stuart Mill, who famously expressed this in terms that have become known as the “harm principle”; specifically that “the only purpose for which power can be rightfully exercised over any member of a civilized community, against his will, is to prevent harm to others.”
Household food insecurity, nutritional status and morbidity in Brazilian children
Authors: Gubert Muriel Bauermann , Spaniol Ana Maria , Bortolini Gisele Ane , Pérez-Escamilla Rafael
Published: February 2016

Objective

To identify the association of household food insecurity (HFI) with anthropometric status, the risk of vitamin A deficiency and anaemia, morbidities such as cough and fever, and hospitalizations for diarrhoea and pneumonia in children under 5 years old.

Design

Cross-sectional study using data from the 2006 Brazilian Demographic and Health Survey. HFI was measured with the Brazilian Food Insecurity Measurement Scale (EBIA). Vitamin A deficiency and anaemia were assessed in blood samples. Child morbidities were reported by the child’s mother and included cough, fever, and hospitalizations for diarrhoea and pneumonia. Regression results were expressed as unadjusted and adjusted OR and corresponding 95 % CI for severe food insecurity, with statistical significance set atP<0·05.

Setting

Nationally representative survey.

Subjects

Children (n4064) under 5 years old.

Results

There was no association between HFI and vitamin A deficiency, pneumonia, wasting or overweight. The prevalence of cough, fever, hospitalization for diarrhoea and stunting were associated with degree of HFI severity. There was a significant association of morbidities and stunting with severe food insecurity (v. food secure). After controlling for confounders, the association between severe food insecurity (v. food secure/rest of food insecurity categories) and the prevalence of common morbidities remained strong, showing that severely food-insecure children had a greater likelihood of experiencing cough (adjusted OR=1·79) and of being hospitalized for diarrhoea (adjusted OR=2·55).

Conclusions

Severe HFI was associated with cough and severe diarrhoea among Brazilian children.
Pigment Degradation in Oil Paint Induced by Indoor Climate: Comparison of Visual and Computational Backscattered Electron Images
Authors: Keune Katrien , Kramer Rick P. , Huijbregts Zara , Schellen Henk L. , Stappers Marc H.L. , van Eikema Hommes Margriet H.
Published: February 2016

For the first time the degradation of lead white pigment in mature oil paint has been used as an internal marker for the degree of saponification and hence chemical degradation of oil paint. Computational image analysis of the backscattered electron images quantified the degree of the intact lead white pigment versus the nonpigmented and lead-rich areas (degraded lead white) in the paint layers. This new methodology was applied to a series of paint samples taken from four painted wall hangings (dated 1778), which makes it possible to study the influence of indoor climate on chemical degradation of aged oil paintings. The visual interpretation and computational image analysis of the backscattered electron images revealed clear trends. The highest degree of lead white degradation in the room was found in samples from the north wall close to the windows, whereas degradation diminished further away from the window. Lead white from the south wall was less degraded, but showed a similar trend as in the paintings on the north wall. These results imply a strong relationship between chemical degradation of paint and location of the paint in the room.
New Space Weather Forecast Technique Fails to Improve Forecasts
Authors: Zastrow Mark
Published: February 2016

For years, scientists have proposed upgrading the National Oceanic and Atmospheric Administration's solar storm forecasts to account for their tilt as they streak toward Earth. But does it help?
Insect pathogenicity in plant-beneficial pseudomonads: phylogenetic distribution and comparative genomics
Authors: Flury Pascale , Aellen Nora , Ruffner Beat , Péchy-Tarr Maria , Fataar Shakira , Metla Zane , Dominguez-Ferreras Ana , Bloemberg Guido , Frey Joachim , Goesmann Alexander , Raaijmakers Jos M , Duffy Brion , Höfte Monica , Blom Jochen , Smits Theo H M , Keel Christoph , Maurhofer Monika
Published: February 2016

Bacteria of the genus Pseudomonas occupy diverse environments. The Pseudomonas fluorescens group is particularly well-known for its plant-beneficial properties including pathogen suppression. Recent observations that some strains of this group also cause lethal infections in insect larvae, however, point to a more versatile ecology of these bacteria. We show that 26 P. fluorescens group strains, isolated from three continents and covering three phylogenetically distinct sub-clades, exhibited different activities toward lepidopteran larvae, ranging from lethal to avirulent. All strains of sub-clade 1, which includes Pseudomonas chlororaphis and Pseudomonas protegens, were highly insecticidal regardless of their origin (animals, plants). Comparative genomics revealed that strains in this sub-clade possess specific traits allowing a switch between plant- and insect-associated lifestyles. We identified 90 genes unique to all highly insecticidal strains (sub-clade 1) and 117 genes common to all strains of sub-clade 1 and present in some moderately insecticidal strains of sub-clade 3. Mutational analysis of selected genes revealed the importance of chitinase C and phospholipase C in insect pathogenicity. The study provides insight into the genetic basis and phylogenetic distribution of traits defining insecticidal activity in plant-beneficial pseudomonads. Strains with potent dual activity against plant pathogens and herbivorous insects have great potential for use in integrated pest management for crops.
Whole-genome mutational burden analysis of three pluripotency induction methods
Authors: Bhutani Kunal , Nazor Kristopher L. , Williams Roy , Tran Ha , Dai Heng , Džakula Željko , Cho Edward H. , Pang Andy W. C. , Rao Mahendra , Cao Han , Schork Nicholas J. , Loring Jeanne F.
Published: February 2016

There is concern that the stresses of inducing pluripotency may lead to deleterious DNA mutations in induced pluripotent stem cell (iPSC) lines, which would compromise their use for cell therapies. Here we report comparative genomic analysis of nine isogenic iPSC lines generated using three reprogramming methods: integrating retroviral vectors, non-integrating Sendai virus and synthetic mRNAs. We used whole-genome sequencing and de novo genome mapping to identify single-nucleotide variants, insertions and deletions, and structural variants. Our results show a moderate number of variants in the iPSCs that were not evident in the parental fibroblasts, which may result from reprogramming. There were only small differences in the total numbers and types of variants among different reprogramming methods. Most importantly, a thorough genomic analysis showed that the variants were generally benign. We conclude that the process of reprogramming is unlikely to introduce variants that would make the cells inappropriate for therapy.
Nonmagnetic band gap at the Dirac point of the magnetic topological insulator (Bi1−xMnx)2Se3
Authors: Sánchez-Barriga J. , Varykhalov A. , Springholz G. , Steiner H. , Kirchschlager R. , Bauer G. , Caha O. , Schierle E. , Weschke E. , Ünal A. A. , Valencia S. , Dunst M. , Braun J. , Ebert H. , Minár J. , Golias E. , Yashina L. V. , Ney A. , Holý V. , Rader O.
Published: February 2016

Magnetic doping is expected to open a band gap at the Dirac point of topological insulators by breaking time-reversal symmetry and to enable novel topological phases. Epitaxial (Bi1−xMnx)2Se3 is a prototypical magnetic topological insulator with a pronounced surface band gap of ∼100 meV. We show that this gap is neither due to ferromagnetic order in the bulk or at the surface nor to the local magnetic moment of the Mn, making the system unsuitable for realizing the novel phases. We further show that Mn doping does not affect the inverted bulk band gap and the system remains topologically nontrivial. We suggest that strong resonant scattering processes cause the gap at the Dirac point and support this by the observation of in-gap states using resonant photoemission. Our findings establish a mechanism for gap opening in topological surface states which challenges the currently known conditions for topological protection.
Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses
Authors: Holm Christian K. , Rahbek Stine H. , Gad Hans Henrik , Bak Rasmus O. , Jakobsen Martin R. , Jiang Zhaozaho , Hansen Anne Louise , Jensen Simon K. , Sun Chenglong , Thomsen Martin K. , Laustsen Anders , Nielsen Camilla G. , Severinsen Kasper , Xiong Yingluo , Burdette Dara L. , Hornung Veit , Lebbink Robert Jan , Duch Mogens , Fitzgerald Katherine A. , Bahrami Shervin , Mikkelsen Jakob Giehm , Hartmann Rune , Paludan Søren R.
Published: February 2016

Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.
Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells
Authors: Ramirez Michael , Rajaram Satwik , Steininger Robert J. , Osipchuk Daria , Roth Maike A. , Morinishi Leanna S. , Evans Louise , Ji Weiyue , Hsu Chien-Hsiang , Thurley Kevin , Wei Shuguang , Zhou Anwu , Koduru Prasad R. , Posner Bruce A. , Wu Lani F. , Altschuler Steven J.
Published: February 2016

Cancer therapy has traditionally focused on eliminating fast-growing populations of cells. Yet, an increasing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a ‘persister’ state of negligible growth. This drug-tolerant state has been hypothesized to be part of an initial strategy towards eventual acquisition of bona fide drug-resistance mechanisms. However, the diversity of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here we compare persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We find, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies acquired diverse resistance mechanisms, including the most commonly observed clinical resistance mechanisms. Thus, the drug-tolerant persister state does not limit—and may even provide a latent reservoir of cells for—the emergence of heterogeneous drug-resistance mechanisms.
A competitive and reversible deactivation approach to catalysis-based quantitative assays
Authors: Koide Kazunori , Tracey Matthew P. , Bu Xiaodong , Jo Junyong , Williams Michael J. , Welch Christopher J.
Published: February 2016

Catalysis-based signal amplification makes optical assays highly sensitive and widely useful in chemical and biochemical research. However, assays must be fine-tuned to avoid signal saturation, substrate depletion and nonlinear performance. Furthermore, once stopped, such assays cannot be restarted, limiting the dynamic range to two orders of magnitude with respect to analyte concentrations. In addition, abundant analytes are difficult to quantify under catalytic conditions due to rapid signal saturation. Herein, we report an approach in which a catalytic reaction competes with a concomitant inactivation of the catalyst or consumption of a reagent required for signal generation. As such, signal generation proceeds for a limited time, then autonomously and reversibly stalls. In two catalysis-based assays, we demonstrate restarting autonomously stalled reactions, enabling accurate measurement over five orders of magnitude, including analyte levels above substrate concentration. This indicates that the dynamic range of catalysis-based assays can be significantly broadened through competitive and reversible deactivation.
Unfolding the physics of URu2Si2 through silicon to phosphorus substitution
Authors: Gallagher A. , Chen K.-W. , Moir C. M. , Cary S. K. , Kametani F. , Kikugawa N. , Graf D. , Albrecht-Schmitt T. E. , Riggs S. C. , Shekhter A. , Baumbach R. E.
Published: February 2016

The heavy fermion intermetallic compound URu2Si2 exhibits a hidden-order phase below the temperature of 17.5 K, which supports both anomalous metallic behavior and unconventional superconductivity. While these individual phenomena have been investigated in detail, it remains unclear how they are related to each other and to what extent uranium f-electron valence fluctuations influence each one. Here we use ligand site substituted URu2Si2-xPx to establish their evolution under electronic tuning. We find that while hidden order is monotonically suppressed and destroyed for x≤0.035, the superconducting strength evolves non-monotonically with a maximum near x≈0.01 and that superconductivity is destroyed near x≈0.028. This behavior reveals that hidden order depends strongly on tuning outside of the U f-electron shells. It also suggests that while hidden order provides an environment for superconductivity and anomalous metallic behavior, it’s fluctuations may not be solely responsible for their progression.
Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders
Authors: Werling Donna M. , Parikshak Neelroop N. , Geschwind Daniel H.
Published: February 2016

Autism spectrum disorder (ASD) is more prevalent in males, and the mechanisms behind this sex-differential risk are not fully understood. Two competing, but not mutually exclusive, hypotheses are that ASD risk genes are sex-differentially regulated, or alternatively, that they interact with characteristic sexually dimorphic pathways. Here we characterized sexually dimorphic gene expression in multiple data sets from neurotypical adult and prenatal human neocortical tissue, and evaluated ASD risk genes for evidence of sex-biased expression. We find no evidence for systematic sex-differential expression of ASD risk genes. Instead, we observe that genes expressed at higher levels in males are significantly enriched for genes upregulated in post-mortem autistic brain, including astrocyte and microglia markers. This suggests that it is not sex-differential regulation of ASD risk genes, but rather naturally occurring sexually dimorphic processes, potentially including neuron–glial interactions, that modulate the impact of risk variants and contribute to the sex-skewed prevalence of ASD.
Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
Authors: Chua Song Lin , Yam Joey Kuok Hoong , Hao Piliang , Adav Sunil S. , Salido May Margarette , Liu Yang , Givskov Michael , Sze Siu Kwan , Tolker-Nielsen Tim , Yang Liang
Published: February 2016

Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a ‘last-resort’ antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections.
Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer’s disease
Authors: Sehlin Dag , Fang Xiaotian T. , Cato Linda , Antoni Gunnar , Lannfelt Lars , Syvänen Stina
Published: February 2016

Owing to their specificity and high-affinity binding, monoclonal antibodies have potential as positron emission tomography (PET) radioligands and are currently used to image various targets in peripheral organs. However, in the central nervous system, antibody uptake is limited by the blood–brain barrier (BBB). Here we present a PET ligand to be used for diagnosis and evaluation of treatment effects in Alzheimer’s disease. The amyloid β (Aβ) antibody mAb158 is radiolabelled and conjugated to a transferrin receptor antibody to enable receptor-mediated transcytosis across the BBB. PET imaging of two different mouse models with Aβ pathology clearly visualize Aβ in the brain. The PET signal increases with age and correlates closely with brain Aβ levels. Thus, we demonstrate that antibody-based PET ligands can be successfully used for brain imaging.
YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity
Authors: Hwang Soo Seok , Jang Sung Woong , Kim Min Kyung , Kim Lark Kyun , Kim Bong-Sung , Kim Hyeong Su , Kim Kiwan , Lee Wonyong , Flavell Richard A. , Lee Gap Ryol
Published: February 2016

Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for Treg-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in Treg cells than Tconv cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in Treg cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of Treg cells by blocking Foxp3.
Preventive obesity agent montmorillonite adsorbs dietary lipids and enhances lipid excretion from the digestive tract
Authors: Xu Pengfei , Dai Shu , Wang Jing , Zhang Jun , Liu Jin , Wang Fang , Zhai Yonggong
Published: February 2016

Western diets are typically high in fat and are associated with long-term complications such as obesity and hepatic steatosis. Because of the enjoyable taste of high-fat diets (HFDs), we are interested in determining how to decrease lipid absorption and enhance lipid excretion from the digestive tract after the consumption of eating fatty foods. Montmorillonite was initially characterized as a gastrointestinal mucosal barrier protective agent for the treatment of diarrhoea. Dietary lipid adsorbent- montmorillonite (DLA-M) was isolated and purified from Xinjiang montmorillonite clay via the water extraction method. Here, we show that DLA-M has an unexpected role in preventing obesity, hyperlipidaemia and hepatic steatosis in HFD-fed rats. Interestingly, combined application of polarized light microscopy and lipid staining analyses, showed that DLA-M crystals have dietary lipid-adsorbing ability in vitro and in vivo, which enhances lipid excretion via bowel movements. In summary, our results indicate that DLA-M prevent HFD-induced obesity. This novel dietary lipid-adsorbing agent can help prevent obesity and its comorbidities.
Identification of novel secreted fatty acids that regulate nitrogen catabolite repression in fission yeast
Authors: Sun Xiaoying , Hirai Go , Ueki Masashi , Hirota Hiroshi , Wang Qianqian , Hongo Yayoi , Nakamura Takemichi , Hitora Yuki , Takahashi Hidekazu , Sodeoka Mikiko , Osada Hiroyuki , Hamamoto Makiko , Yoshida Minoru , Yashiroda Yoko
Published: February 2016

Uptake of poor nitrogen sources such as branched-chain amino acids is repressed in the presence of high-quality nitrogen sources such as NH4+ and glutamate (Glu), which is called nitrogen catabolite repression. Amino acid auxotrophic mutants of the fission yeast Schizosaccharomyces pombe were unable to grow on minimal medium containing NH4Cl or Glu even when adequate amounts of required amino acids were supplied. However, growth of these mutant cells was recovered in the vicinity of colonies of the prototrophic strain, suggesting that the prototrophic cells secrete some substances that can restore uptake of amino acids by an unknown mechanism. We identified the novel fatty acids, 10(R)-acetoxy-8(Z)-octadecenoic acid and 10(R)-hydroxy-8(Z)-octadecenoic acid, as secreted active substances, referred to as Nitrogen Signaling Factors (NSFs). Synthetic NSFs were also able to shift nitrogen source utilization from high-quality to poor nitrogen sources to allow adaptive growth of the fission yeast amino acid auxotrophic mutants in the presence of high-quality nitrogen sources. Finally, we demonstrated that the Agp3 amino acid transporter was involved in the adaptive growth. The data highlight a novel intra-species communication system for adaptation to environmental nutritional conditions in fission yeast.
On the Chemistry and Physical Properties of Flux and Floating Zone Grown SmB6 Single Crystals
Authors: Phelan W. A. , Koohpayeh S. M. , Cottingham P. , Tutmaher J. A. , Leiner J. C. , Lumsden M. D. , Lavelle C. M. , Wang X. P. , Hoffmann C. , Siegler M. A. , Haldolaarachchige N. , Young D. P. , McQueen T. M.
Published: February 2016

Recent theoretical and experimental findings suggest the long-known but not well understood low temperature resistance plateau of SmB6 may originate from protected surface states arising from a topologically non-trivial bulk band structure having strong Kondo hybridization. Yet others have ascribed this feature to impurities, vacancies and surface reconstructions. Given the typical methods used to prepare SmB6 single crystals, flux and floating-zone procedures, such ascriptions should not be taken lightly. We demonstrate how compositional variations and/or observable amounts of impurities in SmB6 crystals grown using both procedures affect the physical properties. From X-ray diffraction, neutron diffraction and X-ray computed tomography experiments we observe that natural isotope containing (SmB6) and doubly isotope enriched (154Sm11B6) crystals prepared using aluminum flux contain co-crystallized, epitaxial aluminum. Further, a large, nearly stoichiometric crystal of SmB6 was successfully grown using the float-zone technique; upon continuing the zone melting, samarium vacancies were introduced. These samarium vacancies drastically alter the resistance and plateauing magnitude of the low temperature resistance compared to stoichiometric SmB6. These results highlight that impurities and compositional variations, even at low concentrations, must be considered when collecting/analyzing physical property data of SmB6. Finally, a more accurate samarium-154 coherent neutron scattering length, 8.9(1) fm, is reported.
OCT-based label-free in vivo lymphangiography within human skin and areola
Authors: Baran Utku , Qin Wan , Qi Xiaoli , Kalkan Goknur , Wang Ruikang K.
Published: February 2016

Due to the limitations of current imaging techniques, visualization of lymphatic capillaries within tissue in vivo has been challenging. Here, we present a label-free high resolution optical coherence tomography (OCT) based lymphangiography (OLAG) within human skin in vivo. OLAG enables rapid (~seconds) mapping of lymphatic networks, along with blood vessel networks, over 8 mm x 8 mm of human skin and 5 mm x 5 mm of human areola. Moreover, lymphatic system’s response to inflammation within human skin is monitored throughout an acne lesion development over 7 days. The demonstrated results promise OLAG as a revolutionary tool in the clinical research and treatment of patients with pathologic conditions such as cancer, diabetes and autoimmune diseases.
Heme oxygenase-1 induction attenuates imiquimod-induced psoriasiform inflammation by negative regulation of Stat3 signaling
Authors: Zhang Bin , Xie Sijing , Su Zhonglan , Song Shiyu , Xu Hui , Chen Gang , Cao Wangsen , Yin Shasha , Gao Qian , Wang Hongwei
Published: February 2016

Heme oxygenase-1 (HO-1), a stress-inducible protein with a potential anti-inflammatory effect, plays an important role in skin injury and wound healing. However, the function of HO-1 in cutaneous inflammatory diseases, such as psoriasis, remains unknown. The abnormal activation of Stat3, a known transcription factor that induces inflammation and regulates cell differentiation, is directly involved in the pathogenesis and development of psoriasis. Hence, targeting Stat3 is potentially beneficial in the treatment of psoriasis. In this study, HO-1 activation significantly alleviated the disease-related pathogenesis abnormality. To determine the mechanism by which HO-1 exerts immune protection on Th17-related cytokines, IL6/IL22-induced Stat3 activation was significantly suppressed, accompanied by decreased cell proliferation and reversed abnormal cell proliferation. Importantly, HO-1-induced Stat3 suppression was mediated through the activation of protein tyrosine phosphatase SHP-1. Overall, our study provides direct evidence indicating that HO-1 might be a useful therapeutic target for psoriasis. SHP-1-mediated suppression of Stat3 activation after HO-1 activation is a unique molecular mechanism for the regulation of Stat3 activation.
A block mixture model to map eQTLs for gene clustering and networking
Authors: Wang Ningtao , Gosik Kirk , Li Runze , Lindsay Bruce , Wu Rongling
Published: February 2016

To study how genes function in a cellular and physiological process, a general procedure is to classify gene expression profiles into categories based on their similarity and reconstruct a regulatory network for functional elements. However, this procedure has not been implemented with the genetic mechanisms that underlie the organization of gene clusters and networks, despite much effort made to map expression quantitative trait loci (eQTLs) that affect the expression of individual genes. Here we address this issue by developing a computational approach that integrates gene clustering and network reconstruction with genetic mapping into a unifying framework. The approach can not only identify specific eQTLs that control how genes are clustered and organized toward biological functions, but also enable the investigation of the biological mechanisms that individual eQTLs perturb in a signaling pathway. We applied the new approach to characterize the effects of eQTLs on the structure and organization of gene clusters in Caenorhabditis elegans. This study provides the first characterization, to our knowledge, of the effects of genetic variants on the regulatory network of gene expression. The approach developed can also facilitate the genetic dissection of other dynamic processes, including development, physiology and disease progression in any organisms.
Chemical Partition of the Radiative Decay Rate of Luminescence of Europium Complexes
Authors: Lima Nathalia B. D. , Dutra José Diogo L. , Gonçalves Simone M. C. , Freire Ricardo O. , Simas Alfredo M.
Published: February 2016

The spontaneous emission coefficient, Arad, a global molecular property, is one of the most important quantities related to the luminescence of complexes of lanthanide ions. In this work, by suitable algebraic transformations of the matrices involved, we introduce a partition that allows us to compute, for the first time, the individual effects of each ligand on Arad, a property of the molecule as a whole. Such a chemical partition thus opens possibilities for the comprehension of the role of each of the ligands and their interactions on the luminescence of europium coordination compounds. As an example, we applied the chemical partition to the case of repeating non-ionic ligand ternary complexes of europium(III) with DBM, TTA and BTFA, showing that it allowed us to correctly order, in an a priori manner, the non-obvious pair combinations of non-ionic ligands that led to mixed-ligand compounds with larger values of Arad.
Neural basis of uncertain cue processing in trait anxiety
Authors: Zhang Meng , Ma Chao , Luo Yanyan , Li Ji , Li Qingwei , Liu Yijun , Ding Cody , Qiu Jiang
Published: February 2016

Individuals with high trait anxiety form a non-clinical group with a predisposition for an anxiety-related bias in emotional and cognitive processing that is considered by some to be a prerequisite for psychiatric disorders. Anxious individuals tend to experience more worry under uncertainty and processing uncertain information is an important, but often overlooked factor in anxiety. So, we decided to explore the brain correlates of processing uncertain information in individuals with high trait anxiety using the learn-test paradigm. Behaviorally, the percentages on memory test and the likelihood ratios of identifying novel stimuli under uncertainty were similar to the certain fear condition, but different from the certain neutral condition. The brain results showed that the visual cortex, bilateral fusiform gyrus and right parahippocampal gyrus were active during the processing of uncertain cues. Moreover, we found that trait anxiety was positively correlated with the BOLD signal of the right parahippocampal gyrus during the processing of uncertain cues. No significant results were found in the amygdala during uncertain cue processing. These results suggest that memory retrieval is associated with uncertain cue processing, which is underpinned by over-activation of the right parahippocampal gyrus, in individuals with high trait anxiety.
Extracellular Forces Cause the Nucleus to Deform in a Highly Controlled Anisotropic Manner
Authors: Haase Kristina , Macadangdang Joan K. L. , Edrington Claire H. , Cuerrier Charles M. , Hadjiantoniou Sebastian , Harden James L. , Skerjanc Ilona S. , Pelling Andrew E.
Published: February 2016

Physical forces arising in the extra-cellular environment have a profound impact on cell fate and gene regulation; however the underlying biophysical mechanisms that control this sensitivity remain elusive. It is hypothesized that gene expression may be influenced by the physical deformation of the nucleus in response to force. Here, using 3T3s as a model, we demonstrate that extra-cellular forces cause cell nuclei to rapidly deform (<1 s) preferentially along their shorter nuclear axis, in an anisotropic manner. Nuclear anisotropy is shown to be regulated by the cytoskeleton within intact cells, with actin and microtubules resistant to orthonormal strains. Importantly, nuclear anisotropy is intrinsic, and observed in isolated nuclei. The sensitivity of this behaviour is influenced by chromatin organization and lamin-A expression. An anisotropic response to force was also highly conserved amongst an array of examined nuclei from differentiated and undifferentiated cell types. Although the functional purpose of this conserved material property remains elusive, it may provide a mechanism through which mechanical cues in the microenvironment are rapidly transmitted to the genome.
Association of long-term blood pressure variability and brachial-ankle pulse wave velocity: a retrospective study from the APAC cohort
Authors: Wang Yang , Yang Yuling , Wang Anxin , An Shasha , Li Zhifang , Zhang Wenyan , Liu Xuemei , Ruan Chunyu , Liu Xiaoxue , Guo Xiuhua , Zhao Xingquan , Wu Shouling
Published: February 2016

We investigated associations between long-term blood pressure variability (BPV) and brachial-ankle pulse wave velocity (baPWV). Within the Asymptomatic Polyvascular Abnormalities Community (APAC) study, we retrospectively collected long-term BPV and baPWV measures. Long-term BPV was calculated using the mean and standard deviation of systolic blood pressure (SBP) across 4 years based on annual values of SBP. In total, 3,994 subjects (2,284 men) were eligible for inclusion in this study. We stratified the study population into four SBP quartiles. Left and right baPWV was higher in participants with long-term SBPV in the fourth quartile compared with the first quartile (left: 1,725 ± 488 vs. 1,461 ± 340 [p < 0.001]; right: 1,722 ± 471 vs. 1,455 ± 341 [p < 0.001], respectively). We obtained the same result for total baPWV (fourth vs. first quartile: 1,772 ± 429 vs. 1,492 ± 350 [p < 0.001]). Furthermore, there was a trend for gradually increased baPWV (≥1,400 cm/s) with increased SBPV (p < 0.001). After multivariable adjustment, baPWV was positively correlated with long-term BPV (p < 0.001). In conclusion, long-term BPV is significantly associated with arterial stiffness as assessed by baPWV.
Weak localization effect in topological insulator micro flakes grown on insulating ferrimagnet BaFe12O19
Authors: Zheng Guolin , Wang Ning , Yang Jiyong , Wang Weike , Du Haifeng , Ning Wei , Yang Zhaorong , Lu Hai-Zhou , Zhang Yuheng , Tian Mingliang
Published: February 2016

Many exotic physics anticipated in topological insulators require a gap to be opened for their topological surface states by breaking time reversal symmetry. The gap opening has been achieved by doping magnetic impurities, which however inevitably create extra carriers and disorder that undermine the electronic transport. In contrast, the proximity to a ferromagnetic/ferrimagnetic insulator may improve the device quality, thus promises a better way to open the gap while minimizing the side-effects. Here, we grow thin single-crystal Sb1.9Bi0.1Te3 micro flakes on insulating ferrimagnet BaFe12O19 by using the van der Waals epitaxy technique. The micro flakes show a negative magnetoresistance in weak perpendicular fields below 50 K, which can be quenched by increasing temperature. The signature implies the weak localization effect as its origin, which is absent in intrinsic topological insulators, unless a surface state gap is opened. The surface state gap is estimated to be 10 meV by using the theory of the gap-induced weak localization effect. These results indicate that the magnetic proximity effect may open the gap for the topological surface attached to BaM insulating ferrimagnet. This heterostructure may pave the way for the realization of new physical effects as well as the potential applications of spintronics devices.
Comparative genomics and functional analysis of the 936 group of lactococcal Siphoviridae phages
Authors: Murphy James , Bottacini Francesca , Mahony Jennifer , Kelleher Philip , Neve Horst , Zomer Aldert , Nauta Arjen , van Sinderen Douwe
Published: February 2016

Genome sequencing and comparative analysis of bacteriophage collections has greatly enhanced our understanding regarding their prevalence, phage-host interactions as well as the overall biodiversity of their genomes. This knowledge is very relevant to phages infecting Lactococcus lactis, since they constitute a significant risk factor for dairy fermentations. Of the eighty four lactococcal phage genomes currently available, fifty five belong to the so-called 936 group, the most prevalent of the ten currently recognized lactococcal phage groups. Here, we report the genetic characteristics of a new collection of 936 group phages. By combining these genomes to those sequenced previously we determined the core and variable elements of the 936 genome. Genomic variation occurs across the 936 phage genome, such as genetic elements that (i) lead to a +1 translational frameshift resulting in the formation of additional structures on the phage tail, (ii) specify a double neck passage structure, and (iii) encode packaging module-associated methylases. Hierarchical clustering of the gene complement of the 936 group phages and nucleotide alignments allowed grouping of the ninety 936 group phages into distinct clusters, which in general appear to correspond with their geographical origin.
Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers
Authors: Gupta Rajinder K. , Himashree G. , Singh Krishan , Soree Poonam , Desiraju Koundinya , Agrawal Anurag , Ghosh Dishari , Dass Deepak , Reddy Prassana K. , Panjwani Usha , Singh Shashi Bala
Published: February 2016

Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility.
Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na+/Ca2+ exchanger
Authors: Zhu Jingzhen , Dong Xingyou , Liu Qian , Wu Chao , Wang Qingqing , Long Zhou , Li Longkun
Published: February 2016

Hydrophobic bile acids (BAs) are thought to inhibit smooth muscle contractility in several organs. The present study was undertaken to investigate the effects of hydrophobic BAs on the detrusor contractility of rat bladder and to explore the possible mechanism. Lithocholic acid (LCA) treatment increased the micturition interval and induced a concentration-dependent relaxation of bladder detrusor strips. In addition, LCA reduced the concentration of intracellular free Ca2+([Ca2+]i) and inhibited both the outward and inward Na+/Ca2+ exchanger (NCX) current (INCX) in primary isolated smooth muscle cells (SMCs). To further investigate the mechanism of action of LCA, several pharmacologic agents were used. We found that the NCX inhibitor 3′,4′-Dichlorobenzamil (DCB) can significantly inhibit the relaxation of detrusor strips and a reduction of the [Ca2+]i induced by LCA, while the antagonist of muscarinic receptor and the agonist of the G protein-coupled bile acid receptor (TGR5) and the farnesoid X receptor (FXR) had no effect. In conclusion, these data suggest that the relaxation of rat detrusor induced by hydrophobic BAs is mediated by NCX. Further research is needed to carry out to demonstrate the possible pathway and provide a potential new strategy to investigation for the treatment of the low urinary tract syndromes.