bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance
Authors: Kim Seungsoo , Lieberman Tami D. , Kishony Roy
Published: September 2014

Significance

Antibiotic resistance is a growing threat, but the pace of drug discovery remains slow. Combination therapy can inhibit the emergence of de novo resistance but is often too toxic for long-term use. Alternating treatments, in which drugs are used sequentially with periodic switching, have been proposed as a substitute, but it remains uncertain when and how they slow the evolution of resistance. Using experimental evolution and whole-genome sequencing, we find that alternating drugs slows the rate of increase in resistance compared with single-drug treatments, by constraining resistance mutations with trade-offs in resistance to a second drug. Thus, drug combinations can exploit these trade-offs to slow the evolution of resistance, even when the drugs are not used simultaneously.
Antifreeze protein-induced superheating of ice inside Antarctic notothenioid fishes inhibits melting during summer warming
Authors: Cziko Paul A. , DeVries Arthur L. , Evans Clive W. , Cheng Chi-Hing Christina
Published: September 2014

Significance

Antarctic notothenioid fishes are protected from freezing by antifreeze proteins (AFPs) that bind to invading ice crystals and inhibit their growth. Paradoxically, accumulation of AFP-stabilized ice could be lethal. Whether and how fishes eliminate internal ice is unknown; one hypothesis is that it melts during summer warming episodes. However, prior in vitro evidence indicates that AFPs also inhibit melting. Our study establishes that pronounced melting inhibition occurs in vivo (i.e., superheated ice occurs inside notothenioid fishes). Our long-term temperature record of a high-latitude Antarctic fish habitat indicates that summer warming does not overcome AFP-induced superheating to reliably rid fishes of ice. Evolution of the life-saving AFPs exacts a cost: the risk of lifelong accumulation of damaging internal ice crystals.
Deleting titin’s I-band/A-band junction reveals critical roles for titin in biomechanical sensing and cardiac function
Authors: Granzier Henk L. , Hutchinson Kirk R. , Tonino Paola , Methawasin Mei , Li Frank W. , Slater Rebecca E. , Bull Mathew M. , Saripalli Chandra , Pappas Christopher T. , Gregorio Carol C. , Smith John E.
Published: September 2014

Significance

Mutations in titin are a major cause of heart failure, yet the functions of large parts of titin are not understood. Here we studied titin’s I-band/A-band junction that has been proposed to be crucial for thick filament length control. We made a mouse in which titin’s IA junction was deleted. Super-resolution microscopy (structured illumination microscopy) revealed that deleting the IA junction increases the strain on titin’s molecular spring elements without altering thick filament length. Single cell biomechanical measurements showed that this increases passive stiffness while functional studies at the whole animal level revealed diastolic dysfunction, exercise intolerance, and modest concentric cardiac hypertrophy—signature features of heart failure with preserved ejection fraction. Our studies support that titin is a promising therapeutic target for treating heart failure.
Iron oxides stimulate sulfate-driven anaerobic methane oxidation in seeps
Authors: Sivan Orit , Antler Gilad , Turchyn Alexandra V. , Marlow Jeffrey J. , Orphan Victoria J.
Published: September 2014

Significance

Anaerobic oxidation of methane (AOM) coupled to sulfate reduction has been shown to consume up to 90% of the greenhouse gas methane produced within the subseafloor environment; however, the mechanism of this process has remained enigmatic. Here, we provide geochemical evidence based on sulfur, oxygen, and carbon isotopes for the involvement of iron oxides in sulfate-driven AOM in methane seeps. Our results suggest that, beyond the function of iron as nutrient, the presence of iron oxides stimulates sulfate-driven AOM to a greater extent than in sediments with low concentrations of iron oxides. The isotope analyses further indicate that sulfate reduction in methane seep habitats differs than sulfate reduction in diffusive profiles in and above the sulfate–methane transition zone.
NODULE INCEPTION creates a long-distance negative feedback loop involved in homeostatic regulation of nodule organ production
Authors: Soyano Takashi , Hirakawa Hideki , Sato Shusei , Hayashi Makoto , Kawaguchi Masayoshi
Published: September 2014

Significance

Long-range organ-to-organ communications are important for the coordination of development and environmental adaptation in multicellular organisms, particularly plants that continuously produce postembryonic lateral organs in various environmental conditions. The substance of homeostatic regulation of organ development via long-distance signals has not yet been identified, however. Legumes use an autoregulatory negative-feedback system involving root–shoot communication to maintain optimal numbers of nodules by systemically suppressing nodulation. We show that a transcription factor, NODULE INCEPTION (NIN), an essential inducer for nodule primordium formation, directly activates genes encoding small peptides that act as root-derived long-distance mobile signals, leading to repression of endogenous
NIN
though the root–shoot communication and resulting in systemic suppression of nodulation. We demonstrate that an autoregulatory negative-feedback loop homeostatically regulates nodule production via this long-range signaling.
Multistep hierarchical self-assembly of chiral nanopore arrays
Authors: Kim Hanim , Lee Sunhee , Shin Tae Joo , Korblova Eva , Walba David M. , Clark Noel A. , Lee Sang Bok , Yoon Dong Ki
Published: September 2014

Significance

Bent-core mesogenic molecules form smectic liquid crystal phases in which the molecular layers are locally polar and chiral, and have a built-in tendency for saddle splay curvature, a combination that fills bulk neat bent-core smectics with self-assembled helical nanofilament bundles of twisted layers. This observation led us to explore the growth mode of such smectics under conditions of nanoconfinement and the remarkable observation reported here that single nanofilaments readily grow in linear nanoscale pores, generating a new motif of hierarchically self-assembled hybrid organic/inorganic structures for applications in chiral synthesis and separation.
Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling
Authors: Han Joo Seok , Vitre Benjamin , Fachinetti Daniele , Cleveland Don W.
Published: September 2014

Significance

The mitotic checkpoint (or the spindle assembly checkpoint) ensures genome integrity by preventing premature chromosome segregation. The pathway is triggered locally by kinetochores, multiprotein complexes assembled onto centromeres. Unattached kinetochores produce Mad2 bound to Cdc20, the mitotic activator of the E3 ubiquitin ligase APC/C. The initial Mad2–Cdc20 complex is then converted into the final mitotic checkpoint inhibitor Bub3–BubR1–Cdc20 that blocks APC/C (anaphase promoting complex or cyclosome)-dependent ubiquitination of cyclin B and securin, thereby stabilizing them and preventing an advance to anaphase. In this study, we identify dual mechanisms by which Bub3 promotes mitotic checkpoint signaling. Bub3 binding to BubR1 promotes two distinct BubR1–Cdc20 interactions, one acting at unattached kinetochores and the other cytoplasmically to facilitate production of the mitotic checkpoint inhibitor.
α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation
Authors: Burré Jacqueline , Sharma Manu , Südhof Thomas C.
Published: September 2014

Significance

Physiologically, α-synuclein promotes soluble NSF attachment protein receptor (SNARE) complex assembly during synaptic exocytosis. Pathologically, however, α-synuclein forms neurotoxic aggregates that promote neurodegeneration and represent hallmarks of Parkinson's disease and other synucleinopathies. α-Synuclein exists in a monomeric unfolded state in solution and in an α-helical folded state upon binding to membranes. Yet the relation between these conformational states and their physiological and pathological roles remain unknown. Here, we demonstrate that α-synuclein multimerizes during membrane binding and that the membrane-bound, multimeric form of α-synuclein mediates SNARE complex assembly in presynaptic terminals. Our data delineate a folding pathway for α-synuclein that ranges from a monomeric unfolded form in cytosol to a physiologically functional multimeric form that is membrane bound and chaperones SNARE complex assembly, and that may protect against neurodegeneration.
Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles
Authors: Kong Dong , Farmer Veronica , Shukla Anil , James Jana , Gruskin Richard , Kiriyama Shigeo , Loncarek Jadranka
Published: September 2014

Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells.
Progressive replacement of embryo-derived cardiac macrophages with age
Authors: Molawi Kaaweh , Wolf Yochai , Kandalla Prashanth K. , Favret Jeremy , Hagemeyer Nora , Frenzel Kathrin , Pinto Alexander R. , Klapproth Kay , Henri Sandrine , Malissen Bernard , Rodewald Hans-Reimer , Rosenthal Nadia A. , Bajenoff Marc , Prinz Marco , Jung Steffen , Sieweke Michael H.
Published: September 2014

Cardiac macrophages (cMΦ) are critical for early postnatal heart regeneration and fibrotic repair in the adult heart, but their origins and cellular dynamics during postnatal development have not been well characterized. Tissue macrophages can be derived from embryonic progenitors or from monocytes during inflammation. We report that within the first weeks after birth, the embryo-derived population of resident CX3CR1+ cMΦ diversifies into MHCII+ and MHCII− cells. Genetic fate mapping demonstrated that cMΦ derived from CX3CR1+ embryonic progenitors persisted into adulthood but the initially high contribution to resident cMΦ declined after birth. Consistent with this, the early significant proliferation rate of resident cMΦ decreased with age upon diversification into subpopulations. Bone marrow (BM) reconstitution experiments showed monocyte-dependent quantitative replacement of all cMΦ populations. Furthermore, parabiotic mice and BM chimeras of nonirradiated recipient mice revealed a slow but significant donor contribution to cMΦ. Together, our observations indicate that in the heart, embryo-derived cMΦ show declining self-renewal with age and are progressively substituted by monocyte-derived macrophages, even in the absence of inflammation.
NAIL, a software toolset for inferring, analyzing and visualizing regulatory networks
Authors: Hurley Daniel G. , Cursons Joseph , Wang Yi Kan , Budden David M. , Print Cristin G. , Crampin Edmund J.
Published: September 2014

Summary : The wide variety of published approaches for the problem of regulatory network inference makes using multiple inference algorithms complex and time-consuming. Network Analysis and Inference Library (NAIL) is a set of software tools to simplify the range of computational activities involved in regulatory network inference. It uses a modular approach to connect different network inference algorithms to the same visualization and network-based analyses. NAIL is technology-independent and includes an interface layer to allow easy integration of components into other applications.

Availability and implementation : NAIL is implemented in MATLAB, runs on Windows, Linux and OSX, and is available from SourceForge at https://sourceforge.net/projects/nailsystemsbiology/ for all researchers to use.

Contact : daniel.hurley@unimelb.edu.au

Supplementary information : Supplementary data are available at Bioinformatics online.
Reproducibility of telomere length assessment: an international collaborative study
Authors: Martin-Ruiz Carmen M , Baird Duncan , Roger Laureline , Boukamp Petra , Krunic Damir , Cawthon Richard , Dokter Martin M , van der Harst Pim , Bekaert Sofie , de Meyer Tim , Roos Goran , Svenson Ulrika , Codd Veryan , Samani Nilesh J , McGlynn Liane , Shiels Paul G , Pooley Karen A , Dunning Alison M , Cooper Rachel , Wong Andrew , Kingston Andrew , von Zglinicki Thomas
Published: September 2014

Background: Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories.

Methods: We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques.

Results: Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63–0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant ( P  = 0.06). Gel-based and PCR-based techniques were not different in accuracy.

Conclusions: Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories.
Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes
Authors: Li Xiaobing , Saitoh Shin-ichiroh , Shibata Takuma , Tanimura Natsuko , Fukui Ryutaro , Miyake Kensuke
Published: September 2014

Toll-like receptor 7 (TLR7) and TLR9 sense microbial single-stranded RNA (ssRNA) and ssDNA in endolysosomes. Nucleic acid (NA)-sensing in endolysosomes is thought to be important for avoiding TLR7/9 responses to self-derived NAs. Aberrant self-derived NA transportation to endolysosomes predisposes to autoimmune diseases. To restrict NA-sensing in endolysosomes, TLR7/9 trafficking is tightly controlled by a multiple transmembrane protein Unc93B1. In contrast to TLR7/9 trafficking, little is known about a mechanism underlying NA transportation. We here show that Mucolipin 1 (Mcoln1), a member of the transient receptor potential (TRP) cation channel gene family, has an important role in ssRNA trafficking into lysosomes. Mcoln1−/− dendritic cells (DCs) showed impaired TLR7 responses to ssRNA. A mucolipin agonist specifically enhanced TLR7 responses to ssRNAs. The channel activity of Mcoln1 is activated by a phospholipid phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), which is generated by a class III lipid kinase PIKfyve. A PIKfyve inhibitor completely inhibited TLR7 responses to ssRNA in DCs. Confocal analyses showed that ssRNA transportation to lysosomes in DCs was impaired by PIKfyve inhibitor as well as by the lack of Mcoln1. Transportation of TLR9 ligands was also impaired by the PIKfyve inhibitor. These results demonstrate that the PtdIns(3,5)P2–Mcoln1 axis has an important role in ssRNA transportation into lysosomes in DCs.
Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis
Authors: Iinuma Chihiro , Waki Masashi , Kawakami Ai , Yamaguchi Madoka , Tomaru Utano , Sasaki Naomi , Masuda Sakiko , Matsui Yuki , Iwasaki Sari , Baba Tomohisa , Kasahara Masanori , Yoshiki Takashi , Paletta Daniel , Herrmann Thomas , Ishizu Akihiro
Published: September 2014

We previously generated a rat model that spontaneously developed small vessel vasculitis (SVV). In this study, a T cell clone reactive with rat vascular endothelial cells (REC) was established and named VASC-1. Intravenous injection of VASC-1 induced SVV in normal recipients. VASC-1 was a TCRαβ/CD3-positive CD4/CD8 double-negative T cell clone with expression of NKG2D. The cytokine mRNA profile under unstimulated condition was positive for IL-4 and IFN-γ but negative for IL-2 and IL-10. After interaction with REC, the mRNA expression of IL-2, IL-5 and IL-6 was induced in VASC-1, which was inhibited by blocking of CD1d on the REC surface. Although the protein levels of these cytokines seemed to be lower than the detection limit in the culture medium, IFN-γ was detectable. The production of IFN-γ from the VASC-1 stimulated with LPS-pre-treated REC was inhibited by the CD1d blockade on the REC. These findings indicated VASC-1 as an NKT cell clone. The NKT cell pool includes two major subsets, namely types I and II. Type I NKT cells are characterized by expression of semi-invariant TCRs and the potential to bind to marine sponge-derived α-galactosylceramide (α-GalCer) loaded on CD1d; whereas, type II NKT cells do not manifest these characteristics. VASC-1 exhibited a usage of TCR other than the type I invariant TCR α chain and did not bind to α-GalCer-loaded CD1d; therefore, it was determined as a type II NKT cell clone. The collective evidence suggested that REC-reactive type II NKT cells could be involved in the pathogenesis of SVV in rats.
Unleashing the clinical power of T cells: CD19/CD3 bi-specific T cell engager (BiTE®) antibody construct blinatumomab as a potential therapy
Authors: Zimmerman Zachary , Maniar Tapan , Nagorsen Dirk
Published: September 2014

Multi-agent chemotherapy is the standard treatment for most B cell malignancies. Since chemotherapy can be associated with significant toxicity and since relapses resistant to chemotherapy often develop, new therapies are needed. Blinatumomab (AMG 103 or MT103) is a late-stage candidate in clinical development, which belongs to a novel class of antibody constructs termed bi-specific T cell engager antibodies. This antibody construct has dual specificity for CD19 and CD3 and can re-direct polyclonal cytotoxic T lymphocytes toward the tumor. This review focuses on the pre-clinical and clinical development of blinatumomab as a powerful new tool in the treatment of B cell malignancies.
Accuracy of Noninvasive Intraocular Pressure or Optic Nerve Sheath Diameter Measurements for Predicting Elevated Intracranial Pressure in Cryptococcal Meningitis
Authors: Nabeta Henry W. , Bahr Nathan C. , Rhein Joshua , Fossland Nicholas , Kiragga Agnes N. , Meya David B. , Dunlop Stephen J. , Boulware David R.
Published: September 2014

Background.  Cryptococcal meningitis is associated with increased intracranial pressure (ICP). Therapeutic lumbar puncture (LP) is recommended when the initial ICP is >250 mm H2O, yet the availability of manometers in Africa is limited and not always used where available. We assessed whether intraocular pressure could be a noninvasive surrogate predictor to determine when additional therapeutic LPs are necessary.

Methods.  Ninety-eight human immunodeficiency virus-infected Ugandans with suspected meningitis (81% Cryptococcus) had intraocular pressure measured using a handheld tonometer (n = 78) or optic nerve sheath diameter (ONSD) measured by ultrasound (n = 81). We determined the diagnostic performance of these methods for predicting ICP vs a standard manometer.

Results.  The median ICP was 225 mm H2O (interquartile range [IQR], 135–405 mm H2O). The median intraocular pressure was 28 mm Hg (IQR, 22–37 mm Hg), and median ultrasound ONSD was 5.4 mm (IQR, 4.95–6.1 mm). ICP moderately correlated with intraocular pressure (ρ = 0.45, P < .001) and with ultrasound ONSD (ρ = 0.44, P < .001). There were not discrete threshold cutoff values for either tonometry or ultrasound ONSD that provided a suitable cutoff diagnostic value to predict elevated ICP (>200 mm H2O). However, risk of elevated ICP >200 mm H2O was increased with an average intraocular pressure >28 mm Hg (relative risk [RR] = 3.03; 95% confidence interval [CI], 1.55–5.92; P < .001) or an average of ONSD >5 mm (RR = 2.39; 95% CI, 1.42–4.03; P = .003). As either intraocular pressure or ONSD increased, probability of elevated ICP increased (ie, positive predictive value increased).

Conclusions.  Noninvasive intraocular pressure measurements by tonometry or ultrasound correlate with cerebrospinal fluid opening pressure, but both are a suboptimal replacement for actual ICP measurement with a manometer.
Investigation of Cardiomyopathy in Children With Cirrhotic and Noncirrhotic Portal Hypertension
Authors: Celtik Coskun , Durmaz Ozlem , Oner Naci , Yavuz Taner , Gökce Selim , Aydogan Aysen , Nisli Kemal , Emiroglu H. Haldun , Ömeroglu Rukiye E. , Sökücü Semra
Published: September 2014

Background:

Cirrhotic cardiomyopathy (CCMP) is a functional disorder characterized by electrophysiological disturbances, and diastolic and/or systolic dysfunction in patients with liver disease. This disorder is a well‐defined entity in adults, but pediatric data are limited. The aim of the study was to determine the incidence, features, and risk factors of CCMP in children with portal hypertension (PHT).

Methods:

This study included 50 children with cirrhotic PHT (40/50) and noncirrhotic PHT (10/50). Fifty healthy children were also selected for the control group. Electrocardiography and echocardiography were used to evaluate cardiac functions. Corrected QT (QTc) ≥ 0.45 was accepted as prolonged on electrocardiography. The study group was divided into 3 groups: cirrhotic, noncirrhotic, and control. Then, the CCMP group was created according to the diagnostic criteria. Latent CCMP was diagnosed in the presence of prolonged‐QTc along with a minor criterion (tachycardia). Manifest CCMP was diagnosed in the presence of at least 2 major criteria (prolonged‐QTc along with abnormal echocardiographic findings). Moreover, in this study, the risk factors for CCMP were investigated.

Results:

The CCMP group included 10 cases (20%). Nine of these cases had latent CCMP (18%), and the remaining one (2%) had manifest CCMP. All of the cases with CCMP had cirrhosis and ascites. None of the patients with CCMP had severe cardiac symptoms, but they were already using some cardioprotective drugs such as propanolol and spironolactone. As risk factors for CCMP, pediatric end‐stage liver disease scores, Child‐Pugh scores, and ascites grades were found to be significant for the determination of CCMP. The most important risk factor was ascites severity (P = 0.001, odds ratio 9.4).

Conclusions:

Approximately 20% of children with PHT have CCMP. A detailed cardiac examination should be carried out periodically in children with cirrhotic PHT, especially in the presence of ascites and high Child‐Pugh score.
Response of laser-localized structures to external perturbations in coupled semiconductor microcavities
Authors: Turconi M. , Giudici M. , Barland S.
Published: September 2014

Laser-localized structures have been observed in several experiments based on broad-area semiconductor lasers. They appear as bounded regions of laser light emission which can exist independently of each other and are expected to be commuted via external optical perturbations. In this work, we perform a statistical analysis of time-resolved commutation experiments in a system of coupled lasers and show the role of wavelength, polarization and pulse energy in the switching process. Furthermore, we also analyse the response of the system outside of the stability region of laser-localized states in search of an excitable response. We observe not only a threshold separating two types of responses, but also a strong variability in the system's trajectory when returning to the initial stable fixed point.
Cavity solitons in vertical-cavity surface-emitting lasers
Authors: Vladimirov A. G. , Pimenov A. , Gurevich S. V. , Panajotov K. , Averlant E. , Tlidi M.
Published: September 2014

We investigate a control of the motion of localized structures (LSs) of light by means of delay feedback in the transverse section of a broad area nonlinear optical system. The delayed feedback is found to induce a spontaneous motion of a solitary LS that is stationary and stable in the absence of feedback. We focus our analysis on an experimentally relevant system, namely the vertical-cavity surface-emitting laser (VCSEL). We first present an experimental demonstration of the appearance of LSs in a 80 μm aperture VCSEL. Then, we theoretically investigate the self-mobility properties of the LSs in the presence of a time-delayed optical feedback and analyse the effect of the feedback phase and the carrier lifetime on the delay-induced spontaneous drift instability of these structures. We show that these two parameters affect strongly the space–time dynamics of two-dimensional LSs. We derive an analytical formula for the threshold associated with drift instability of LSs and a normal form equation describing the slow time evolution of the speed of the moving structure.
Time-delayed feedback control of breathing localized structures in a three-component reaction–diffusion system
Authors: Gurevich Svetlana V.
Published: September 2014

The dynamics of a single breathing localized structure in a three-component reaction–diffusion system subjected to time-delayed feedback is investigated. It is shown that variation of the delay time and the feedback strength can lead either to stabilization of the breathing or to delay-induced periodic or quasi-periodic oscillations of the localized structure. A bifurcation analysis of the system in question is provided and an order parameter equation is derived that describes the dynamics of the localized structure in the vicinity of the Andronov–Hopf bifurcation. With the aid of this equation, the boundaries of the stabilization domains as well as the dependence of the oscillation radius on delay parameters can be explicitly derived, providing a robust mechanism to control the behaviour of the breathing localized structure in a straightforward manner.
Light–matter interaction induces a single positive vortex with swirling arms
Authors: Barboza R. , Bortolozzo U. , Clerc M. G. , Residori S. , Vidal-Henriquez E.
Published: September 2014

Homeotropic nematic liquid crystal cells with a photosensitive wall and negative dielectric anisotropy exhibit, under the influence of local illumination, stable vortexes with swirling arms that are trapped at the illuminated area. Close to the Fréedericksz transition an amplitude equation is derived, which allows us to understand the origin of the induced vortex and the competition between the illuminating profile and the elastic anisotropy generating the swirling of the arms.
Lactobacillus gorillae sp. nov., isolated from the faeces of captive and wild western lowland gorillas (Gorilla gorilla gorilla)
Authors: Tsuchida Sayaka , Kitahara Maki , Nguema Pierre Philippe Mbehang , Norimitsu Saeko , Fujita Shiho , Yamagiwa Juichi , Ngomanda Alfred , Ohkuma Moriya , Ushida Kazunari
Published: September 2014

Four strains of Gram-staining-positive, anaerobic rods were isolated from the faeces of western lowland gorillas (Gorilla gorilla gorilla). Three strains, KZ01T, KZ02 and KZ03, were isolated at the Kyoto City Zoo, Japan, and one strain, GG02, was isolated in the Moukalaba-Doudou National Park, Gabon. These strains were investigated taxonomically. These strains belonged to the

Lactobacillus reuteri

phylogenetic group according to phylogenetic analysis based on 16S rRNA gene sequences and specific phenotypic characteristics. Phylogenetic analysis of their 16S rRNA gene sequences revealed that strains KZ01T, KZ02, KZ03 and GG02 formed a single monophyletic cluster and had a distinct line of descent. Based on sequence similarity of the 16S rRNA gene,

Lactobacillus fermentum

JCM 1173T (96.6 %) was the closest neighbour to these novel strains, although it was clear that these strains belonged to a different species. Partial pheS sequences also supported these relationships. DNA–DNA relatedness between strain KZ01T and

L. fermentum

JCM 1173T was less than 22 % and the DNA G+C content of strain KZ01T was 50.7 mol%. The cell-wall peptidoglycan type was A4β (l-Orn–d-Asp) and the major fatty acids were C16 : 0, C18 : 1ω9c and C19 : 1 cyclo 9,10. Therefore, based on phylogenetic, phenotypic and physiological evidence, these strains represent a novel species of the genus

Lactobacillus

, for which the name Lactobacillus gorillae sp. nov. is proposed. The type strain is KZ01T ( = JCM 19575T = DSM 28356T).
ISEcp1-mediated transposition of bla
KPC into the chromosome of a clinical isolate of Acinetobacter baumannii from Puerto Rico
Authors: Martínez Teresa , Vázquez Guillermo J. , Aquino Edna E. , Martínez Idalí , Robledo Iraida E.
Published: September 2014

Carbapenems are the last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacilli. Klebsiella pneumoniae carbapenemase (KPC) hydrolyses β-lactam antibiotics including the carbapenems. KPCs have been detected in Enterobacteriaceae and Pseudomonas aeruginosa isolates worldwide associated with transposon Tn4401 commonly located in plasmids. Acinetobacter baumannii has become an important multidrug-resistant nosocomial pathogen capable of hydrolysing the carbapenem antibiotics. KPC-producing A. baumannii has so far only been reported in Puerto Rico. During a surveillance study, four KPC-producing A. baumannii with identical pulse type were identified in a single institution. The objectives of this study were to characterize the KPC genetic background and the allelic diversity of one of the isolates. Next-generation sequencing and multilocus sequence typing (MLST) were performed. Molecular characterization of the isolate demonstrated bla
KPC in Tn4401b located in the bacterial chromosome within a 26.5 kb DNA fragment, which included a KQ-like element (18.9 kb) very similar to that described previously in a K. pneumoniae plasmid and a 7.6 kb DNA fragment with 98 % homology to a putative plasmid from Yersinia pestis strain PY-95. Our data suggested that the 26.5 kb DNA fragment harbouring bla
KPC was integrated in the chromosome by a transposition event mediated by the transposase of ISEcp1 found in the KQ-like element. MLST showed a novel sequence type, ST250. To our knowledge, this is the first report of the identification of the genetic background of bla
KPC in A. baumannii.
MUSiCC: A marker genes based framework for metagenomic normalization and accurate profiling of gene abundances in the microbiome
Authors: Manor Ohad , Borenstein Elhanan
Published: September 2014

Functional metagenomic analyses commonly involve a normalization step, where measured levels of genes or pathways are converted into relative abundances. Here, we demonstrate that this normalization scheme introduces marked biases both across and within human microbiome samples and systematically identify various sample-and gene-specific properties that contribute to these biases. We introduce an alternative normalization paradigm, MUSiCC, which combines universal single-copy genes with machine learning methods to correct these biases and to obtain a more accurate and biologically meaningful measure of gene abundances. Finally, we demonstrate that MUSiCC significantly improves downstream discovery of functional shifts in the microbiome.

MUSiCC is available athttp://elbo.gs.washington.edu/software.html.
Molecular phenotypes that are causal to complex traits can have low heritability and are expected to have small influence
Authors: Parts Leopold
Published: September 2014

Work on genetic makeup of complex traits has led to some unexpected findings. Molecular trait heritability estimates have consistently been lower than those of common diseases, even though it is intuitively expected that the genotype signal weakens as it becomes more dissociated from DNA. Further, results from very large studies have not been sufficient to explain most of the heritable signal, and suggest hundreds if not thousands of responsible alleles. Here, I demonstrate how trait heritability depends crucially on the definition of the phenotype, and is influenced by the variability of the assay, measurement strategy, and the quantification approach used. For a phenotype downstream of many molecular traits, it is possible that its heritability is larger than for any of its upstream determinants. I also rearticulate via models and data that if a phenotype has many dependencies, a large number of small effect alleles are expected. However, even if these alleles do drive highly heritable causal intermediates that can be modulated, it does not imply that large changes in phenotype can be obtained.
Phenylcoumaran Benzylic Ether Reductase Prevents Accumulation of Compounds Formed under Oxidative Conditions in Poplar Xylem
Authors: Niculaes Claudiu , Morreel Kris , Kim Hoon , Lu Fachuang , McKee Lauren S. , Ivens Bart , Haustraete Jurgen , Vanholme Bartel , Rycke Riet De , Hertzberg Magnus , Fromm Jorg , Bulone Vincent , Polle Andrea , Ralph John , Boerjan Wout
Published: September 2014

Phenylcoumaran benzylic ether reductase (PCBER) is one of the most abundant proteins in poplar (Populus spp) xylem, but its biological role has remained obscure. In this work, metabolite profiling of transgenic poplar trees downregulated in PCBER revealed both the in vivo substrate and product of PCBER. Based on mass spectrometry and NMR data, the substrate was identified as a hexosylated 8–5-coupling product between sinapyl alcohol and guaiacylglycerol, and the product was identified as its benzyl-reduced form. This activity was confirmed in vitro using a purified recombinant PCBER expressed in Escherichia coli. Assays performed on 20 synthetic substrate analogs revealed the enzyme specificity. In addition, the xylem of PCBER-downregulated trees accumulated over 2000-fold higher levels of cysteine adducts of monolignol dimers. These compounds could be generated in vitro by simple oxidative coupling assays involving monolignols and cysteine. Altogether, our data suggest that the function of PCBER is to reduce phenylpropanoid dimers in planta to form antioxidants that protect the plant against oxidative damage. In addition to describing the catalytic activity of one of the most abundant enzymes in wood, we provide experimental evidence for the antioxidant role of a phenylpropanoid coupling product in planta.
Crystal structure of 4-((1E)-1-{(2Z)-2-[4-(4-bromophenyl)-3-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene}ethyl)phenol hemihydrate
Authors: Mague Joel T. , Akkurt Mehmet , Mohamed Shaaban K. , Hassan Alaa A. , Albayati Mustafa R.
Published: September 2014

In the title compound, C23H18BrN3OS·0.5H2O, the bromophenyl, phenyl and phenol rings make dihedral angles of 46.5 (1), 66.78 (8) and 15.4 (2)°, respectively, with the mean squares plane of the thiazolidene ring. In the crystal, the lattice water molecule is hydrogen bonded to the phenol group and makes a weaker O—H...N connection to an inversion-related molecule, forming a ring while weak pairwise C—H...S interactions involving inversion-related molecules form a second ring. Both these motifs result in the formation of two-dimensional networks lying parallel to (10-1).
Crystal structure of bis{2-[(E)-(4-fluorobenzyl)iminomethyl]phenolato-κ2N,O}nickel(II)
Authors: Tajuddin Amalina Mohd , Bahron Hadariah , Hanafiah Rohazila Mohammad , Ibrahim Nazlina , Fun Hoong-Kun , Chantrapromma Suchada
Published: September 2014

The asymmetric unit of the title complex, [Ni(C14H11FNO)2], contains one-half of the molecule with the NiIIcation lying on an inversion centre coordinated by a bidentate Schiff base anion. The cationic NiIIcenter is in a distorted square-planar coordination environment chelated by the imine N and phenolate O donor atoms of the two Schiff base ligands. The N and O donor atoms of the two ligands are mutuallytranswith Ni—N and Ni—O bond lengths of 1.9242 (10) and 1.8336 (9) Å, respectively. The fluorophenyl ring is almost orthogonal to the coordination plane and makes a dihedral angle of 82.98 (7)° with the phenolate ring. In the crystal, molecules are linked into screw chains by weak C—H...F hydrogen bonds. Additional C—H...π contacts arrange the molecules into sheets parallel to theacplane.
Crystal structure of the cage derivative pentacyclo[5.4.0.02,6.03,10.05,9]undeca-8,11-dione ethylene dithioketal
Authors: Kotha Sambasivarao , Sreenivasachary Nampalli , Deodhar Deepak , Shaikh Mobin
Published: September 2014

The title pentacycloundecane cage derivative, C13H14OS2, was identified during a thioketalization reaction. The reaction selectively gave the title compound and the product corresponding to bis-ketal was not formed. The title compound exhibits unusual Csp3—Csp3single bond lengths ranging from 1.495 (3) to 1.581 (2) and strained bond angles as small as 89.29 (12) and as large as 115.11 (11)°.
Crystal structure of ethyl 2-[(4-bromophenyl)amino]-3,4-dimethylpent-3-enoate
Authors: Zukerman-Schpector Julio , Caracelli I. , Stefani Hélio A. , Khan Amna N. , Tiekink Edward R. T.
Published: September 2014

In the title compound, C15H20BrNO2, there are two independent molecules (AandB) comprising the asymmetric unit and these adopt very similar conformations. InA, the dihedral angle between the CO2and MeC=CMe2groups is 80.7 (3)°, and these make dihedral angles of 3.5 (3) and 84.09 (16)°, respectively, with the bromobenzene ring. The equivalent dihedral angles for moleculeBare 78.4 (3), 2.1 (3) and 78.37 (12)°, respectively. The most prominent interactions in the crystal packing are amine-N—H...O(carbonyl) hydrogen bonds between the two independent molecules, resulting in non-centrosymmetric ten-membered {...OC2NH}2synthons. Statistical disorder is noted for each of the terminal methyl groups of the ethyl residues.
Crystal structure of [(2S)-1-[(3S)-3-carboxy-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl]-1-oxopropan-2-yl][(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]azanium chloride acetonitrile monosolvate
Authors: Li Ai-zhen , Xu Wen-jie
Published: September 2014

The title compound (trivial name moexipril hydrochloride) crystallizes as the acetonitrile monosolvate, C27H35N2O7+·Cl−·C2H3N, with the salt comprising a U-shaped cation and a chloride anion. The conformation of the cation is stabilized by a weak intramolecular N+—H...O hydrogen bond and the tetrahydropyridine ring adopts aboatconformation. The dihedral angle between the planes of the benzene rings is 85.6 (1)°. In the crystal, the cations and anions form tight ionic pairs by strong intermolecular O—H...Cl hydrogen bonds. C—H...Cl and C—H...N hydrogen bonds link these ionic pairs and the acetonitrile solvate molecules into puckered layers parallel to (100).
Tracing Teutonic footprints in VET around the world?
Authors: Pilz Matthias , Li Junmin
Published: September 2014

Purpose

– This paper aims to focus on the vocational and training behaviours of German corporations at their subsidiaries in the USA, China and India. Although all three countries are important markets for Germany, they are characterised by very different cultures, vocational education and training (VET) systems and employment systems. The transfer of the German VET system to other countries has been the topic of discussion and controversy.

Design/methodology/approach

– In this study, the authors rely on interviews with local training experts of German subsidiaries to analyse VET activities. Their analysis is based on convergence (standardisation) versus divergence (localisation) theory borrowed from approaches in international management studies.

Findings

– The findings indicate a “localisation” effect in all three nations. The similarities can be explained partially by the stronger focus on off-the-job trainings and greater preferences for academic careers.

Research limitations/implications

– The study is a pilot study.

Practical implications

– The transfer of the German VET system to other countries seems to be very difficult.

Originality/value

– Beyond this general debate, the specialist literature pays virtually no attention to the training practices of German companies abroad. The authors have tried to fill this research gap.
‘Genre Blurring’ and Public Administration: What Can We Learn from Ethnography?
Authors: Rhodes R. A. W.
Published: September 2014

This article seeks to broaden the craft of public administration by ‘blurring genres’. First, I explain the phrase ‘blurring genres’. Second, I provide some examples of early work in administrative ethnography. Third, I compare this early, modernist‐empiricist ethnography with interpretive ethnography, suggesting researchers confront three choices: naturalism vs. anti‐naturalism; intensive vs. hit‐and‐run fieldwork; and generalisation vs. local knowledge. After this general discussion, and fourth, I discuss the more prosaic issues that confront anyone seeking to use ethnography to study public administration and look at fieldwork roles, relevance, time, evidence and fieldwork relationships. Fifth, I describe and illustrate the several tools students of public administration can use as well as observation and interviews; namely, focus groups, para‐ethnography, visual ethnography, and storytelling. Finally, I conclude that ethnographic fieldwork provides texture, depth and nuance, and lets interviewees explain the meaning of their actions. It is an indispensable tool and a graphic example of how to enrich public administration by drawing on the theories and methods of the humanities.
Anticipating Interpretivism: Heclo and Wildavsky as Pioneers?
Authors: Weller Patrick
Published: September 2014

The Private Government of Public Money, published by Hugh Heclo and Aaron Wildavsky, was a study of the working of the Treasury in Britain. Even if some of the detail is now dated, their bold and innovative approach, portraying Whitehall as a community, was an antidote to the rather formal descriptions that had been the standard early accounts. This article examines the approach they took, assesses its impact on future studies and asks whether they were pioneering the route for future interpretivist studies. It concluded that even if neither of the authors would have been comfortable to be categorised in those terms, they did open up the study of government in a way that has encouraged and enabled later interpretevist research.
Isolation, Identification, and Quantification of Lichenysin, a Novel Nonvolatile Compound in Chinese Distilled Spirits
Authors: Zhang Rong , Wu Qun , Xu Yan , Qian Michael C.
Published: September 2014

Nonvolatile components influence overall flavor volatility and perception in alcoholic beverages. However, little information has been reported about the nonvolatile compounds in Chinese distilled spirits. For the first time, we isolated and identified a cyclic lipopeptide “lichenysin” as a novel nonvolatile compound in Chinese liquors, using preparative high performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometer and nuclear magnetic resonance. The concentrations of lichenysin were quantified in 14 main types of bottled Chinese liquors by using ultra performance liquid chromatography coupled with triple quadrupole mass spectrometer. The concentrations of lichenysin in Chinese liquor ranged from 0.01 to 111.74 μg/L, where the concentration was the highest in Dongjiu liquor. Furthermore, we found that lichenysin selectively affected aroma volatility in the Chinese liquor, using the headspace solid‐phase microextraction coupled with gas chromatography‐mass spectrometry. The headspace concentrations of 2‐phenylethanol, phenol, and 4‐methylphenol significantly decreased by respectively 58%, 76%, and 59% in 3 Chinese commercial liquors with an increase in lichenysin. These results indicated that lichenysin could be a novel nonvolatile compound that selectively affected aroma volatility in Chinese liquors.
Comparative transcriptome resources of eleven Primulina species, a group of ‘stone plants’ from a biodiversity hot spot
Authors: Ai Bin , Gao Yong , Zhang Xiaolong , Tao Junjie , Kang Ming , Huang Hongwen
Published: September 2014

The genus Primulina is an emerging model system in studying the drivers and mechanisms of species diversification, for its high species richness and endemism, together with high degree of habitat specialization. In this study, we sequenced transcriptomes for eleven Primulina species across the phylogeny of the genus using the Illumina HiSeq 2000 platform. A total of 336 million clean reads were processed into 355 573 unigenes with a mean length of 1336 bp and an N50 value of 2191 bp after pooling and reassembling twelve individual pre‐assembled unigene sets. Of these unigenes, 249 973 (70%) were successfully annotated and 256 601 (72%) were identified as coding sequences (CDSs). We identified a total of 38 279 simple sequence repeats (SSRs) and 367 123 single nucleotide polymorphisms (SNPs). Marker validation assay revealed that 354 (27.3%) of the 1296 SSR and 795 (39.6%) of the 2008 SNP loci showed successful genotyping performance and exhibited expected polymorphism profiles. We screened 834 putative single‐copy nuclear genes and proved their high effectiveness in phylogeny construction and estimation of ancestral population parameters. We identified a total of 85 candidate orthologs under positive selection for 46 of the 66 species pairs. This study provided an efficient application of RNA‐seq in development of genomic resources for a group of ‘stone plants’ from south China Karst regions, a biodiversity hot spot of the World. The assembled unigenes with annotations and the massive gene‐associated molecular markers would help guide further molecular systematic, population genetic and ecological genomics studies in Primulina and its relatives.