bluuebunny/crossref_metadata_2025 huggingface dataset:
A methyltransferase required for proper timing of the vernalization response in
Arabidopsis
Authors: Lee Joohyun , Yun Jae-Young , Zhao Wei , Shen Wen-Hui , Amasino Richard M.
Published: January 2015

Significance

Proper timing of flowering is a key factor in reproductive success. Certain plant species require prolonged cold exposure during winter to flower in the spring; however, how plants measure the duration of cold exposure is not well understood. In this study, we describe the identification of a methyltransferase that is required for proper measurement of the duration of cold exposure.
Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists
Authors: Liu Tao , Zhang Yong , Liu Yan , Wang Ying , Jia Haiqun , Kang Mingchao , Luo Xiaozhou , Caballero Dawna , Gonzalez Jose , Sherwood Lance , Nunez Vanessa , Wang Danling , Woods Ashley , Schultz Peter G. , Wang Feng
Published: January 2015

Significance

Many therapeutic proteins suffer from short plasma half-lives and, as a consequence, require frequent injections to be therapeutically effective; this in turn can adversely affect patient compliance and quality of life. In contrast, therapeutic antibodies typically have half-lives of weeks in humans. Consequently, there is considerable interest in generating functional antibodies with agonist or antagonist activities. Based on the structure of a natural bovine antibody with an ultralong, well-folded heavy-chain complementarity-determining region, we have developed a strategy for the generation of functional human antibody–hormone chimeras with biological activities comparable to native hormones and significantly enhanced pharmacological properties. This approach likely provides a general, relatively straightforward platform for generating antibody agonists and antagonists for a range of therapeutic applications.
Population dynamics of islet-infiltrating cells in autoimmune diabetes
Authors: Magnuson Angela M. , Thurber Greg M. , Kohler Rainer H. , Weissleder Ralph , Mathis Diane , Benoist Christophe
Published: January 2015

Significance

In many autoimmune diseases, self-reactive lymphocytes lead to immunocyte infiltration in the target tissue, whose evolution over time is regulated. Such lesions can be well-tolerated and lead to minimal damage, or have more drastic consequences. We show here, for the insulitis of the nonobese diabetic (NOD) mouse model of autoimmune diabetes, that the autoimmune infiltrate is an open and dynamic cell population, with a high turnover and constant reseeding with fresh cells coming from the general lymphoid circulation; this implies that such a lesion is susceptible to extraneous events and influences, which could either provoke overt disease or instill stronger immunosuppression.
Structural insights into mis-regulation of protein kinase A in human tumors
Authors: Cheung Jonah , Ginter Christopher , Cassidy Michael , Franklin Matthew C. , Rudolph Michael J. , Robine Nicolas , Darnell Robert B. , Hendrickson Wayne A.
Published: January 2015

Significance

Mutations in the catalytic subunit of protein kinase A (PKA) have been found in tumors associated with the kidney disorder Cushing’s syndrome and with the rare liver cancer fibrolamellar hepatocellular carcinoma (FL-HCC). Crystal structures and biochemical characterizations of the relevant PKA mutants clarify the molecular basis for disease caused by these mutations. We find contrasting underlying mechanisms for increased PKA signaling in these cancers. In Cushing’s syndrome, the L205R PKA mutation abolishes regulatory-subunit binding, whereas in FL-HCC, the recurring DnaJ–PKA fusion that results from a chromosomal deletion exhibits wild-type characteristics, but is overproduced by a more active promoter. Our findings provide a structural basis for designing selective drugs that may lead to effective treatments for these diseases.
Force-dependent transition in the T-cell receptor β-subunit allosterically regulates peptide discrimination and pMHC bond lifetime
Authors: Das Dibyendu Kumar , Feng Yinnian , Mallis Robert J. , Li Xiaolong , Keskin Derin B. , Hussey Rebecca E. , Brady Sonia K. , Wang Jia-Huai , Wagner Gerhard , Reinherz Ellis L. , Lang Matthew J.
Published: January 2015

Significance

The αβ T-cell receptor (TCR) on mammalian T lymphocytes recognizes intracellular pathogens to afford protective immunity. Detection of various foreign peptides bound to MHC molecules as TCR ligands occurs during immune surveillance where mechanical forces are generated through cell movement. Using single-molecule optical tweezer assays, we show with isolated and complete receptors on single T cells that both sensitivity and specificity of the biological T-lymphocyte response is dependent upon force-based interactions. Our work demonstrates a catch-and-release αβTCR structural conversion correlating with ligand potency wherein a strongly binding/compact state transitions to a weakly binding/extended state. An allosteric mechanism controls bond strength and lifetime, supporting a model in which quaternary αβTCR subunit associations regulate TCR recognition under load.
Tomato extract suppresses the production of proinflammatory mediators induced by interaction between adipocytes and macrophages
Authors: Kim Young-il , Mohri Shinsuke , Hirai Shizuka , Lin Shan , Goto Tsuyoshi , Ohyane Chie , Sakamoto Tomoya , Takahashi Haruya , Shibata Daisuke , Takahashi Nobuyuki , Kawada Teruo
Published: January 2015

Obese adipose tissue is characterized by enhanced macrophage infiltration. A loop involving monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNFα) between adipocytes and macrophages establishes a vicious cycle that augments inflammatory changes and insulin resistance in obese adipose tissue. Tomatoes, one of the most popular crops worldwide, contain many beneficial phytochemicals that improve obesity-related diseases such as diabetes. Some of them have also been reported to have anti-inflammatory properties. In this study, we focused on the potential protective effects of phytochemicals in tomatoes on inflammation. We screened fractions of tomato extract using nitric oxide (NO) assay in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. One fraction, RF52, significantly inhibited NO production in LPS-stimulated RAW264 macrophages. Furthermore, RF52 significantly decreased MCP-1 and TNFα productions. The coculture of 3T3-L1 adipocytes and RAW264 macrophages markedly enhanced MCP-1, TNFα, and NO productions compared with the control cultures; however, the treatment with RF52 inhibited the production of these proinflammatory mediators. These results suggest that RF52 from tomatoes may have the potential to suppress inflammation by inhibiting the production of NO or proinflammatory cytokines during the interaction between adipocytes and macrophages.
Prioritizing—The Task Strategy of the Powerful?
Authors: Schmid Petra C. , Schmid Mast Marianne , Mast Fred W.
Published: January 2015

Previous research has shown that power increases focus on the main goal when distractor information is present. As a result, high-power people have been described as goal-focused. In real life, one typically wants to pursue multiple goals at the same time. There is a lack of research on how power affects how people deal with situations in which multiple important goals are present. To address this question, 158 participants were primed with high or low power or assigned to a control condition, and were asked to perform a dual-goal task with three difficulty levels. We hypothesized and found that high-power primed people prioritize when confronted with a multiple-goal situation. More specifically, when task demands were relatively low, power had no effect; participants generally pursued multiple goals in parallel. However, when task demands were high, the participants in the high-power condition focused on a single goal whereas participants in the low-power condition continued using a dual-task strategy. This study extends existing power theories and research in the domain of goal pursuit.
Haagerup approximation property for quantum reflection groups
Authors: Lemeux François
Published: January 2015

In this paper we prove that the duals of the quantum reflection groups

H
N

s
+

H_N^{s+}

have the Haagerup property for all

N
≥
4

N\ge 4

and

s
∈
[
1
,
∞
)

s\in [1,\infty )

. We use the canonical arrow

π
:
C
(

H
N

s
+

)
→
C
(

S
N
+

)

\pi : C(H_N^{s+})\to C(S_N^+)

onto the quantum permutation groups, and we describe how the characters of

C
(

H

N

s
+

)

C(H_{N}^{s+})

behave with respect to this morphism

π
\pi

thanks to the description of the fusion rules binding irreducible corepresentations of

C
(

H
N

s
+

)

C(H_N^{s+})

as in Banica and Vergnioux, 2009. This allows us to construct states on the central

C
∗

C^*

-algebra

C
(

H
N

s
+

)
0

C(H_N^{s+})_0

generated by the characters of

C
(

H

N

s
+

)

C(H_{N}^{s+})

and to use a fundamental theorem proved by M. Brannan giving a method to construct nets of trace-preserving, normal, unital and completely positive maps on the von Neumann algebra of a compact quantum group

G

\mathbb {G}

of Kac type.
Clofazimine for the Treatment of Multidrug-Resistant Tuberculosis: Prospective, Multicenter, Randomized Controlled Study in China
Authors: Tang Shenjie , Yao Lan , Hao Xiaohui , Liu Yidian , Zeng Linhai , Liu Gang , Li Mingwu , Li Fujian , Wu Meiying , Zhu Yousheng , Sun Hua , Gu Jin , Wang Xiafang , Zhang Zhanjun
Published: January 2015

Background.  Clofazimine (Cfz) has shown activity against Mycobacterium tuberculosis, including multidrug-resistant (MDR) strains in vitro and in animal studies. Here we evaluate the clinical efficacy and tolerability of using Cfz to treat MDR tuberculosis in China.

Methods.  We enrolled 105 patients who had sputum culture–positive MDR tuberculosis in 6 major tuberculosis specialty hospitals in China. Patients were randomly assigned to either the Cfz therapy group (n = 53) or control group (n = 52). Patients in the 2 groups were given 21 months of individual-based chemotherapy regimens based on medication history and drug susceptibility test results. The Cfz therapy group regimens incorporated 100 mg of Cfz once daily for 21 months.

Results.  Three patients in each group discontinued therapy because of side effects or other reasons. Sputum culture conversion to negative was earlier in patients who received Cfz compared with controls (P = .042 by log-rank test). Chest computed tomography showed cavitary changes in 46 patients in the Cfz therapy group and 45 in the control group. Cavity closure was earlier in patient who received Cfz compared with controls (P = .047 by log-rank test). The treatment success rate in the Cfz group was 73.6%, higher than that in control group (53.8%; P = .035). Side effects in skin only occurred in the Cfz group. The rates of skin discoloration and ichthyosis were 94.3% and 47.2%, respectively.

Conclusions.  Using Cfz to treat MDR tuberculosis promotes cavity closure, accelerates sputum culture conversion, and improves treatment success rates.
Aminoglycoside-modifying enzymes determine the innate susceptibility to aminoglycoside antibiotics in rapidly growing mycobacteria
Authors: Maurer Florian P. , Bruderer Vera L. , Castelberg Claudio , Ritter Claudia , Scherbakov Dimitri , Bloemberg Guido V. , Böttger Erik C.
Published: January 2015

Objectives

Infections caused by the rapidly growing mycobacterium (RGM) Mycobacterium abscessus are notoriously difficult to treat due to the innate resistance of M. abscessus to most clinically available antimicrobials. Aminoglycoside antibiotics (AGA) are a cornerstone of antimicrobial chemotherapy against M. abscessus infections, although little is known about intrinsic drug resistance mechanisms. We investigated the role of chromosomally encoded putative aminoglycoside-modifying enzymes (AME) in AGA susceptibility in M. abscessus.

Methods

Clinical isolates of M. abscessus were tested for susceptibility to a series of AGA with different substituents at positions 2′, 3′ and 4′ of ring 1 in MIC assays. Cell-free extracts of M. abscessus type strain ATCC 19977 and Mycobacterium smegmatis strains SZ380 [aac(2′)-Id+], EP10 [aac(2′)-Id−] and SZ461 [aac(2′)-Id+, rrs A1408G] were investigated for AGA acetylation activity using thin-layer chromatography (TLC). Cell-free ribosome translation assays were performed to directly study drug–target interaction.

Results

Cell-free translation assays demonstrated that ribosomes of M. abscessus and M. smegmatis show comparable susceptibility to all tested AGA. MIC assays for M. abscessus and M. smegmatis, however, consistently showed the lowest MIC values for 2′-hydroxy-AGA as compared with 2′-amino-AGA, indicating that an aminoglycoside-2′-acetyltransferase, Aac(2′), contributes to innate AGA susceptibility. TLC experiments confirmed enzymatic activity consistent with Aac(2′). Using M. smegmatis as a model for RGM, acetyltransferase activity was shown to be up-regulated in response to AGA-induced inhibition of protein synthesis.

Conclusions

Our findings point to AME as important determinants of AGA susceptibility in M. abscessus.
Risk factors for acute kidney injury (AKI) in patients treated with polymyxin B and influence of AKI on mortality: a multicentre prospective cohort study
Authors: Rigatto Maria Helena , Behle Tainá F. , Falci Diego R. , Freitas Thiela , Lopes Natane T. , Nunes Mariá , Costa Leonardo W. , Zavascki Alexandre P.
Published: January 2015

Objectives

The objectives of this study were to assess risk factors for acute kidney injury (AKI) in patients treated with polymyxin B, a last resort antibiotic against Gram-negative bacteria, with a focus on dose, and to determine the impact of AKI on mortality of these patients.

Methods

A multicentre prospective cohort study was performed including patients ≥18 years treated with intravenous polymyxin B for ≥48 h. The primary outcome was AKI defined by RIFLE criteria. Secondary outcomes were 30 day mortality and failure stage of AKI. Multivariate analysis with a Cox regression model was performed. The probability of developing AKI was determined in a logistic regression model.

Results

Four-hundred-and-ten patients were included. AKI occurred in 189 (46.1%) patients. Polymyxin B dose ≥150 mg/day was a risk factor for AKI: adjusted HR = 1.95, 95% CI = 1.31–2.89, P = 0.01. Higher weight and age were also independently associated with AKI. The probability of developing AKI significantly increased with doses between 150 and 199 mg/day, regardless of patient weight, with no significant increase with higher doses. Higher weight also increased the risk in patients receiving the same daily doses. AKI was barely associated with increased risk for 30 day mortality (adjusted HR = 1.35, 95% CI = 0.99–1.85, P = 0.06), while ≥150 mg/day did not increase this risk despite its association with AKI.

Conclusions

Polymyxin B total dose is highly related to the risk of AKI, regardless of patient weight. Thirty-day mortality tended to be higher in patients who developed AKI. The relationship between dose, AKI and mortality must be further investigated in studies specifically designed to evaluate this latter outcome.
A KALA-modified lipid nanoparticle containing CpG-free plasmid DNA as a potential DNA vaccine carrier for antigen presentation and as an immune-stimulative adjuvant
Authors: Miura Naoya , Shaheen Sharif M. , Akita Hidetaka , Nakamura Takashi , Harashima Hideyoshi
Published: January 2015

Technologies that delivery antigen-encoded plasmid DNA (pDNA) to antigen presenting cell and their immune-activation are required for the success of DNA vaccines. Here we report on an artificial nanoparticle that can achieve these; a multifunctional envelope-type nanodevice modified with KALA, a peptide that forms α-helical structure at physiological pH (KALA-MEND). KALA modification and the removal of the CpG-motifs from the pDNA synergistically boosted transfection efficacy. In parallel, transfection with the KALA-MEND enhances the production of multiple cytokines and chemokines and co-stimulatory molecules via the Toll-like receptor 9-independent manner. Endosome-fusogenic lipid envelops and a long length of pDNA are essential for this immune stimulation. Furthermore, cytoplasmic dsDNA sensors that are related to the STING/TBK1 pathway and inflammasome are involved in IFN-β and IL-1β production, respectively. Consequently, the robust induction of antigen-specific cytotoxic T-lymphoma activity and the resulting prophylactic and therapeutic anti-tumor effect was observed in mice that had been immunized with bone marrow-derived dendritic cells ex vivo transfected with antigen-encoding pDNA. Collectively, the KALA-MEND possesses dual functions; gene transfection system and immune-stimulative adjuvant, those are both necessary for the successful DNA vaccine.
Evaluating the potential for undesired genomic effects of the piggyBac transposon system in human cells
Authors: Saha Sunandan , Woodard Lauren E. , Charron Elizabeth M. , Welch Richard C. , Rooney Cliona M. , Wilson Matthew H.
Published: January 2015

Non-viral transposons have been used successfully for genetic modification of clinically relevant cells including embryonic stem, induced pluripotent stem, hematopoietic stem and primary human T cell types. However, there has been limited evaluation of undesired genomic effects when using transposons for human genome modification. The prevalence of piggyBac(PB)-like terminal repeat (TR) elements in the human genome raises concerns. We evaluated if there were undesired genomic effects of the PB transposon system to modify human cells. Expression of the transposase alone revealed no mobilization of endogenous PB-like sequences in the human genome and no increase in DNA double-strand breaks. The use of PB in a plasmid containing both transposase and transposon greatly increased the probability of transposase integration; however, using transposon and transposase from separate vectors circumvented this. Placing a eGFP transgene within transposon vector backbone allowed isolation of cells free from vector backbone DNA. We confirmed observable directional promoter activity within the 5′TR element of PB but found no significant enhancer effects from the transposon DNA sequence. Long-term culture of primary human cells modified with eGFP-transposons revealed no selective growth advantage of transposon-harboring cells. PB represents a promising vector system for genetic modification of human cells with limited undesired genomic effects.
Identification and Characterization of the SnTox6-Snn6Interaction in theParastagonospora nodorum–Wheat Pathosystem
Authors: Gao Y. , Faris J. D. , Liu Z. , Kim Y. M. , Syme R. A. , Oliver R. P. , Xu S. S. , Friesen T. L.
Published: January 2015

Parastagonospora nodorum is a necrotrophic fungal pathogen that causes Septoria nodorum blotch (SNB) (formerly Stagonospora nodorum blotch) on wheat. P. nodorum produces necrotrophic effectors (NE) that are recognized by dominant host sensitivity gene products resulting in disease development. The NE–host interaction is critical to inducing NE-triggered susceptibility (NETS). To date, seven NE–host sensitivity gene interactions, following an inverse gene-for-gene model, have been identified in the P. nodorum–wheat pathosystem. Here, we used a wheat mapping population that segregated for sensitivity to two previously characterized interactions (SnTox1-Snn1 and SnTox3-Snn3-B1) to identify and characterize a new interaction involving the NE designated SnTox6 and the host sensitivity gene designated Snn6. SnTox6 is a small secreted protein that induces necrosis on wheat lines harboring Snn6. Sensitivity to SnTox6, conferred by Snn6, was light-dependent and was shown to underlie a major disease susceptibility quantitative trait locus (QTL). No other QTL were identified, even though the P. nodorum isolate used in this study harbored both the SnTox1 and SnTox3 genes. Reverse transcription-polymerase chain reaction showed that the expression of SnTox1 was not detectable, whereas SnTox3 was expressed and, yet, did not play a significant role in disease development. This work expands our knowledge of the wheat–P. nodorum interaction and further establishes this system as a model for necrotrophic specialist pathosystems.
New Method of Controlling Sugarcane Smut using Flutriafol Fungicide
Authors: Bhuiyan Shamsul A. , Croft Barry J. , Tucker Glen R.
Published: January 2015

Sugarcane smut, caused by Sporisorium scitamineum, is one of the most devastating diseases of sugarcane worldwide. Triazole fungicides such as propiconazole and triadimefon have been routinely used as dip treatments to protect seed-cane (stalk cuttings) from infection by sugarcane smut fungus. However, dip treatments can be applied only to mother stock (nursery) planting materials because of the logistics of dipping large quantities of seed-cane and it is difficult to dispose of the large volumes of waste fungicide solution in an environmentally safe manner. There was a need for a new fungicide that can be applied using more practical methods. The efficacy of flutriafol fungicide to control smut was evaluated in inoculated and infected stalks of a highly susceptible cultivar using various application methods. In a 2007 experiment, flutriafol fungicide was equally effective or better in controlling sugarcane smut as a dip than were two fungicides, propiconazole and triadimefon, registered in Australia. In 2009, two experiments determined the effectiveness of flutriafol when applied by mixing with fertilizer or spraying on the seed-cane at planting. All fungicide treatments significantly suppressed smut in one experiment but, in the second experiment, flutriafol-fertilizer mix treatments were ineffective. In 2010, two experiments verified the efficacy and effective rates of flutriafol against sugarcane smut when applied through existing spray equipment designed to spray fungicide on cuttings as they drop into the planting furrow on a commercial planter. Area under the disease progress curve values of smut incidence were reduced significantly to 47 and 56% with low (125 g a.i. ha−1) and high (375 g a.i. ha−1) application rates, respectively, in both experimental sites compared with the inoculated control plots. Sugar yield increased by 46 to 65% in one experiment and 157 to 203% in the second experiment compared with the inoculated control. This research formulated a more practical method of application of flutriafol and suggests greater applications of this fungicide for the management of sugarcane smut.
Identifying Resistance to Crown Rot Caused byColletotrichum gloeosporioidesin Strawberry
Authors: Mangandi Jozer , Peres Natalia A. , Whitaker Vance M.
Published: January 2015

Resistance to Colletotrichum crown rot (CCR, caused by Colletotrichum gloeosporioides) among commercial strawberry cultivars is variable, and increasing host resistance is a goal of the strawberry breeding program at the University of Florida. Twenty-eight accessions of Fragaria virginiana and F. chiloensis, the progenitor species of the cultivated strawberry (F. × ananassa), were evaluated for CCR resistance on artificially inoculated plants in a field trial, along with cultivars and breeding selections. Accessions PI 612320, PI 612323, and PI 551736 and selections FL 10-128 and FL 10-129 had no mortality in either of two seasons. The most susceptible genotypes had mortality between 75 and 100%. In a separate growth-chamber evaluation, seven genotypes were inoculated by spraying a spore suspension onto the crown or by injecting the suspension directly into the crown tissues. Mortality was higher using the injection method but the ranking of the genotypes was similar for both methods, indicating that resistance is expressed within crown tissues. Among the seven genotypes, selections FL 10-128 and FL 10-129 had the lowest mortality regardless of inoculation method, illustrating that a high level of resistance can be found within the cultivated germplasm.
Comparison of Pathogenic Variation among Phakopsora pachyrhizi Isolates Collected from the United States and International Locations, and Identification of Soybean Genotypes Resistant to the U.S. Isolates
Authors: Paul C. , Frederick R. D. , Hill C. B. , Hartman G. L. , Walker D. R.
Published: January 2015

A major constraint in breeding for resistance to soybean rust has been the virulence diversity in Phakopsora pachyrhizi populations. In greenhouse experiments, reactions of 18 soybean genotypes to 24 U.S. isolates from 2007 and 2008 and 4 foreign isolates were compared. Reactions of four differentials (Rpp1 to Rpp4) to these U.S. isolates were also compared with reactions to nine foreign isolates and three U.S. isolates from 2004. Principal component analysis (PCA) of the reaction types grouped the U.S. isolates into a single virulence group, whereas each of the foreign isolates had a unique virulence pattern. In another experiment, reactions of 11 differentials to the 24 U.S. isolates were compared and significant interactions (P < 0.001) were found between the isolates and host genotypes for rust severity and uredinia densities. PCA of these two measures of disease placed the 24 isolates into seven or six aggressiveness groups, respectively. In a third experiment, evaluation of 20 soybean genotypes for resistance to the previously established aggressive groups identified 10 genotypes resistant to isolates representing most of the groups. This study confirmed the pathogenic diversity in P. pachyrhizi populations and identified soybean germplasm with resistance to representative U.S. isolates that can be used in breeding.
Discovery of a Novel General Anesthetic Chemotype Using High-throughput Screening
Authors: McKinstry-Wu Andrew R. , Bu Weiming , Rai Ganesha , Lea Wendy A. , Weiser Brian P. , Liang David F. , Simeonov Anton , Jadhav Ajit , Maloney David J. , Eckenhoff Roderic G.
Published: January 2015

AbstractAbstract

A high-throughput assay based on competitive binding to a soluble protein model was used to screen a library of more than 350,000 compounds for anesthetic-like binding activity. A novel chemotype, the 6-phenylpyridazin-3(2H)-ones, exhibited general anesthetic activity in secondary assays and ultimately in mice.

Supplemental Digital Content is available in the text.

Background:

The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures.

Methods:

Using a novel high-throughput screen employing the fluorescent anesthetic 1-aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein target(s), we screened a 350,000 compound library for competition with 1-aminoanthracene–apoferritin binding. Hit compounds meeting structural criteria had their binding affinities for apoferritin quantified with isothermal titration calorimetry and were tested for γ-aminobutyric acid type A receptor binding using a flunitrazepam binding assay. Chemotypes with a strong presence in the top 700 and exhibiting activity via isothermal titration calorimetry were selected for medicinal chemistry optimization including testing for anesthetic potency and toxicity in an in vivo Xenopus laevis tadpole assay. Compounds with low toxicity and high potency were tested for anesthetic potency in mice.

Results:

From an initial chemical library of more than 350,000 compounds, we identified 2,600 compounds that potently inhibited 1-aminoanthracene binding to apoferritin. A subset of compounds chosen by structural criteria (700) was successfully reconfirmed using the initial assay. Based on a strong presence in both the initial and secondary screens the 6-phenylpyridazin-3(2H)-one chemotype was assessed for anesthetic activity in tadpoles. Medicinal chemistry efforts identified four compounds with high potency and low toxicity in tadpoles, two were found to be effective novel anesthetics in mice.

Conclusion:

The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.
Revisiting Barry Cox and James Hill's theory of superluminal motion: a possible solution to the problem of spinless tachyon localization
Authors: Mantegna Michele
Published: January 2015

In 2012, Barry Cox and James Hill published a new and elegant way to deduce the formulae of extended relativity, developed by Erasmo Recami and others during the 1960s and 1970s. Extended relativity applies to superluminal or FTL (faster than light in the vacuum) particles, calledtachyonsby the late American physicist Gerald Feinberg. However, tachyons generate causality paradoxes in special relativity when used for signalling. These paradoxes are safely removed only in a space–time containing a preferred inertial reference frame. Moreover, quantum properties should be taken into account. They cause further trouble for tachyons because, for instance, spin-zero FTL particles satisfying the Klein–Gordon equation cannot be localized as pointlike particles, contrary to all other known fundamental constituents of matter. Perhaps the most interesting suggestion in Cox and Hill's paper is that a certain freedom is allowed in the theory of superluminal particles as no such particle has been reliably detected until now, so that it is worthwhile exploring theoretical alternatives. We shall prove that an idea from Cox and Hill's paper, when applied not in the context of extended relativity but in the framework of F. R. Tangherlini's absolute synchronization, allows the problem of tachyon localization for spinless particles to be solved.
Serinibacter tropicus sp. nov., an actinobacterium isolated from the rhizosphere of a mangrove, and emended description of the genus Serinibacter
Authors: Hamada Moriyuki , Shibata Chiyo , Nurkanto Arif , Ratnakomala Shanti , Lisdiyanti Puspita , Tamura Tomohiko , Suzuki Ken-ichiro
Published: January 2015

A novel Gram-stain-positive actinobacterium, designated PS-14-7T, was isolated from the rhizosphere of a mangrove on Pramuka Island, Indonesia, and its taxonomic position was investigated using a polyphasic approach. The peptidoglycan type of strain PS-14-7T was A4α and lysine was the diagnostic diamino acid of the peptidoglycan. The predominant menaquinone was MK-8(H4) and the major fatty acids were anteiso-C15 : 0, C16 : 0 and iso-C16 : 0. The DNA G+C content was 72.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain PS-14-7T was closely related to

Serinibacter salmoneus

Kis4-28T (99.6 %). However, DNA–DNA hybridization and phenotypic characteristics revealed that strain PS-14-7T differed from

Serinibacter salmoneus

. Therefore, strain PS-14-7T represents a novel species of the genus

Serinibacter

, for which the name Serinibacter
tropicus sp. nov. is proposed. The type strain is PS-14-7T ( = NBRC 110108T = InaCC A 515T). An emended description of the genus

Serinibacter

is also proposed.
Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploidCapsella bursa-pastoris
Authors: Douglas Gavin M. , Gos Gesseca , Steige Kim A. , Salcedo Adriana , Holm Karl , Josephs Emily B. , Arunkumar Ramesh , Ågren J. Arvid , Hazzouri Khaled M. , Wang Wei , Platts Adrian E. , Williamson Robert J. , Neuffer Barbara , Lascoux Martin , Slotte Tanja , Wright Stephen I.
Published: January 2015

Whole genome duplication events have occurred repeatedly during flowering plant evolution, and there is growing evidence for predictable patterns of gene retention and loss following polyploidization. Despite these important insights, the rate and processes governing the earliest stages of diploidization remain poorly understood, and the relative importance of genetic drift, positive selection and relaxed purifying selection in the process of gene degeneration and loss is unclear. Here, we conduct whole genome resequencing inCapsella bursa-pastoris, a recently formed tetraploid with one of the most widespread species distributions of any angiosperm. Whole genome data provide strong support for recent hybrid origins of the tetraploid species within the last 100-300,000 years from two diploid progenitors in theCapsellagenus. Major-effect inactivating mutations are frequent, but many were inherited from the parental species and show no evidence of being fixed by positive selection. Despite a lack of large-scale gene loss, we observe a decrease in the efficacy of natural selection genome-wide, due to the combined effects of demography, selfing and genome redundancy from whole genome duplication. Our results suggest that the earliest stages of diploidization are associated with quantitative genome-wide decreases in the strength and efficacy of selection rather than rapid gene loss, and that non-functionalization can receive a 'head start' through a legacy of deleterious variants and differential expression originating in parental diploid populations.
PDMQ-Protein Digestion Multi Query software tool to performin silicodigestion of protein/peptide sequences
Authors: Haraszi Reka , Tasi Csongor , Juhasz Angela , Makai Szabolcs
Published: January 2015

Motivation

In silicoenzymatic digestion tools mostly can be used for digestion of single sequence query, which means a significant limitation in their utility when a number of sequences need to be processed. The other limitation of these applications is the selection options of restriction enzymes that are usually allow only simultaneous digestion. Non-conventional proteins such as cereal prolamins require multi-enzyme multi step digestion, and for cereal proteomics experts this type of application is missing.

Results

PDMQ, Protein Digestion Multi Queryapplication was developed having multi query and multi enzyme options and that way can be customized for any digestion protocol.

Availability and implementation

PDMQ is implemented in C# using the .NET framework and can be downloaded fromhttp://www.agrar.mta.hu/_user/browser/File/bioinformatics/ProteinDigestion_v0_0_0_15.rar
Crystal structure of 2-benzylamino-4-p-tolyl-6,7-dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile
Authors: Nagalakshmi R. A. , Suresh J. , Maharani S. , Kumar R. Ranjith , Lakshman P. L. Nilantha
Published: January 2015

The title compound, C23H21N3, comprises a 2-amino-3-cyanopyridine ring fused with a cyclopentane ring. The later adopts an envelope conformation with the central methylene C atom as the flap. The benzyl and andp-tolyl rings are inclined to one another by 56.18 (15)°, and to the pyridine ring by 81.87 (14) and 47.60 (11)°, respectively. In the crystal, molecules are linked by pairs of N—H...Nnitrilehydrogen bonds, forming inversion dimers with anR22(12) ring motif. The dimers are linked by C—H...π and π–π interactions [centroid–centroid distance = 3.7211 (12) Å], forming a three-dimensional framework.
Crystal structure of 2-methyl-4-[(thiophen-2-yl)methylidene]-1,3-oxazol-5(4H)-one
Authors: Sharma Preetika , Subbulakshmi K. N. , Narayana B. , Byrappa K. , Kant Rajni
Published: January 2015

The asymmetric unit of the title compound, C9H7NO2S, contains two crystallographically independent molecules (AandB). Both molecules are almost planar [maximum deviations = 0.047 (1) and 0.090 (1) Å, respectively, for the S atoms] with the oxazole and thiophene rings being inclined to one another by 2.65 (16)° in moleculeAand by 4.55 (15)° in moleculeB. In the crystal, the individual molecules are linkedviaC—H...O hydrogen bonds, forming –A–B–A–B– chains along the [10-1] direction. The chains are linkedviaC—H...π and π–π interactions [intercentroid distances = 3.767 (2) and 3.867 (2) Å] involving inversion-related oxazole and thiophene rings in both molecules, forming a three-dimensional structure.
Crystal structure of aqua[N-(2-oxidobenzyl-κO)-L-leucinato-κ2N,O](1,10-phenanthroline-κ2N,N′)nickel(II) pentahydrate
Authors: Faizi Md. Serajul Haque , Sharkina Natalia O.
Published: January 2015

In the title compound, [Ni(C13H17NO3)(C12H8N2)(H2O)]·5H2O, the NiIIatom is in a distorted octahedral coordination environment provided by the two N atoms of one bidentate phenanthroline ligand and two O atoms and one N atom from a tridentate 2-[(2-hydroxybenzyl)amino]-4-methylpentanoic acid (HAMA) ligand and one water molecule. The complex was prepared by the reaction of nickel(II) nitrate with HAMA in the presence of 1,10-phenanthroline in a 1:1:1 ratio. In the crystal, the complex molecules and solvate water molecules are associatedviaO—H...O hydrogen bonds into a three-dimensional network.
Once upon a time at work: discovering the stories in workplace training
Authors: Stroud Katie
Published: January 2015

Purpose

– The importance of using stories to impact memory is highly explored and documented; however, little guidance exists for how to develop stories in the context of instructional design. The purpose of this paper is to offer a template for conforming workplace training material into stories. With specific examples and reasoning, the author offers a new way to develop training materials based on the framework of a story.

Design/methodology/approach

– Exploring basic storytelling elements learned in grade school, the author combines past experience with general observations on how stories affect the learner. Applying these concepts, she walks the reader through an experience that reveals how the brain interprets stories. She uses her own story with specific examples and reasoning along the way to help you find the stories that already exist in your everyday world.

Findings

– This paper shows, anecdotally, how to build stories around workplace problems for use in training. It suggests that modeling training around the framework of a story helps the audience to process the information as an experience and therefore retain the information longer.

Originality/value

– This paper was designed to help anyone who is responsible for developing instructional content and has been looking for a structured way to frame that content into a story.
Implementing Democratic Equality in Political Parties: Organisational Consequences in theSwedish and theGerman Pirate Parties
Authors: Bolleyer Nicole , Little Conor , von Nostitz Felix‐Christopher
Published: January 2015

This article theorises and empirically assesses some important intra‐organisational implications of maximising democratic equality in political parties both between followers and members and between members and elites. They include weak member commitment, passivity of the rank‐and‐file membership and – depending on party structure – high levels of internal conflict. To substantiate the arguments, two parties that implement principles of democratic equality in their organisations are examined: theSwedish andGerman Pirate parties. These cases show, first, that while organisational structures implementing norms of equality allowed them to rapidly mobilise a considerable following, the same structures systematically reduced their capacity to consolidate support in the longer term – a weakness that might eventually put these parties' survival at risk. Second, they show that differences in the extent to which subnational units provide a foundation for member mobilisation helps to explain variation in the level of internal conflict experienced by these parties.
Heterologous expression and characterization of endocellulase from the Japanese pine sawyer Monochamus saltuarius (MsGHF5)
Authors: Ko Hyunjun , Kwon Hyuk‐Min , Ko Hyun‐Jin , Ryu Ji‐Hyeon , Song Hwi‐Seung , Park Yong Chul
Published: January 2015

In this study, the endocellulase gene from Monochamus saltuarius (MsGHF5) was transformed into Escherichia coli (RosettaBlue(DE3)pLysS strain), and induced by IPTG. The molecular weight of recombinant MsGHF5 (rMsGHF5) was 78 kDa and was expressed as a fusion protein with maltose binding protein in pMAL‐c2 expression vector. Native‐PAGE was conducted with 0.1% carboxymethyl cellulose as a substrate, and the zymogenic bands were observed. The Michaelis constant and maximum velocity of rMsGHF5 were 0.199 mg/mL and 0.034 μmol/min/mL, respectively. The optimal condition for rMsGHF5 occurred at pH 5 and 30°C. Fe2+ and Mn2+ stimulated the activity of rMsGHF5 by 167 and 114% respectively, whereas Cu2+, Hg2+ and Zn2+ inhibited its activity.
Covariation in abscission force and terminal velocity of windborne sibling seeds alters long‐distance dispersal projections
Authors: Teller Brittany J. , Marden James H. , Shea Katriona
Published: January 2015

Despite the fact that seeds are unlikely to be identical – even among siblings within a maternal individual – dispersal models typically use one mean trait value to represent the ability of an entire species to disperse. Previous work has shown that the environmental conditions under which individuals leave the maternal site strongly affect how far seeds will travel. However, less is known about how trait variation within individuals contributes to dispersal or how such variation might interact with abiotic factors.

Here, we develop the use of an ergometer in a novel application to investigate variation in seed traits, specifically the force required for seed abscission and seed terminal velocity, exhibited by seeds from different locations within maternal capitula of the invasive species Carduus nutans (Asteraceae).

We find that seeds from the centre of capitula are significantly easier to liberate and have slower falling velocities than siblings found near the edge of capitula. When abscission force is positively correlated with terminal velocity, slowly falling, easily abscised, central seeds are projected to travel much further than edge seeds on slow winds.

Our experimental and theoretical results, which together show that within‐individual variation can strongly affect model projections of species dispersal, have important implications for our broader understanding of population spread rates, the spatial structure of populations, metapopulation connectivity and gene flow in the landscape.
A high‐resolution panorama camera system for monitoring colony‐wide seabird nesting behaviour
Authors: Lynch Tim P. , Alderman Rachael , Hobday Alistair J.
Published: January 2015

Obtaining accurate and representative demographic metrics for animal populations is critical to many aspects of wildlife monitoring and management. However, at remote animal colonies, metrics derived from sequential counts or other continuous monitoring are often subject to logistical, weather and disturbance challenges. The development of remote camera technologies has assisted monitoring, but limitations in spatial and temporal resolution and sample sizes remain.

Here, we describe the application of a robotic camera system (Gigapan) which takes a tiled sequence of photographs that are automatically stitched together to form high‐resolution panoramas. We demonstrate the application of the Gigapan using data collected during field testing at a shy albatross colony on Albatross Island in northwest Tasmania.

We took daily panoramas over 5 days to estimate mean incubation shift duration, an indirect measure for foraging trip duration, in an existing study area. Similar numbers of occupied nests could be observed at a distance of approximately 100 m in the Gigapan panoramas compared to ground‐based counts (115 and 117, respectively). Of these, birds on 90% of nests visible in the panoramas could be unambiguously identified as marked or unmarked with a small daub of paint throughout the study period and thus a shift change reliably recorded. Gigapan‐based shift duration was estimated using a novel instantaneous statistical method and were longer than estimates earlier in the egg brooding period, potentially revealing a new pattern in shift duration.

This example field application provides proof of concept and demonstration that the relatively low‐cost Gigapan system provides the spatial advantages of aerial photos with the detail and temporal replication of land‐based camera systems. The Gigapan system can extend or enhance traditional data collection methods, particularly for simultaneous observations at distance, of the behaviour of surface nesting colonial seabirds.
On the existence of maximum likelihood estimates for presence‐only data
Authors: Hefley Trevor J. , Hooten Mevin B.
Published: January 2015

Presence‐only data can be used to determine resource selection and estimate a species’ distribution. Maximum likelihood is a common parameter estimation method used for species distribution models. Maximum likelihood estimates, however, do not always exist for a commonly used species distribution model – the Poisson point process.

We demonstrate the issue with conventional maximum likelihood mathematically, using a data example, and a simulation experiment and show alternative estimation methods.

We found that when habitat preferences are strong or the number of presence‐only locations is small, by chance, maximum likelihood coefficient estimates for the Poisson point process model may not exist. We found that several alternative estimation methods can produce reliable estimates, but results will depend on the chosen method.

It is important to identify conditions for which maximum likelihood estimates are unlikely to be identifiable from presence‐only data. In data sets where the maximum likelihood estimates do not exist, penalized likelihood and Bayesian methods will produce coefficient estimates, but these are sensitive to the choice of estimation procedure and prior or penalty term. When sample size is small or it is thought that habitat preferences are strong, we propose a suite of estimation procedures researchers can consider using.
Troubleshooting the potential pitfalls of cross‐fostering
Authors: Winney Isabel , Nakagawa Shinichi , Hsu Yu‐Hsun , Burke Terry , Schroeder Julia
Published: January 2015

Cross‐fostering is the transfer of offspring between their natal environment and a new social environment. This method allows researchers to disentangle the genetic and interacting environmental effects that influence phenotypes, and is popular in both wild and laboratory studies. Here, we discuss three factors that might bias cross‐fostering and influence ecological and evolutionary conclusions if not accommodated.

First, cross‐fostering tends to be spatially and temporally non‐random because heterogeneous breeding conditions can result in clustered breeding attempts. Secondly, cross‐fostering will often change the brood composition because the exchanged broods are unlikely to be precisely matched in age, size and composition. Thirdly, some methods can introduce bias by using a systematically structured subset of the population, leading to a systematically structured data set.

We use a 12‐year case study of wild house sparrows Passer domesticus to demonstrate how to identify these biases with statistical modelling and how to adjust the cross‐fostering protocol according to the identified biases.

In our data set, cross‐fostered nestlings were more likely to survive than non‐cross‐fostered nestlings, but postfledging and overall survival were not affected. Survival differed between cross‐fostering treatments, partially due to temporally nonrandom breeding conditions and nonrandom offspring selection, demonstrating two of the three forms of bias in data from a wild population.

In all cases, we suggest using statistical models to examine whether cross‐fostering opportunities and offspring fitness are affected by nonrandom breeding, changes to the brood composition and biased methodology. We provide guidelines for optimising a cross‐fostering design and reducing inherent bias.