bluuebunny/crossref_metadata_2025 huggingface dataset:
The RNA polymerase clamp interconverts dynamically among three states and is stabilized in a partly closed state by ppGpp
Authors: Duchi Diego , Mazumder Abhishek , Malinen Anssi M. , Ebright Richard H. , Kapanidis Achillefs N.
Published: March 2018

RNA polymerase (RNAP) contains a mobile structural module, the “clamp,” that forms one wall of the RNAP active-center cleft and that has been linked to crucial aspects of the transcription cycle, including loading of promoter DNA into the RNAP active-center cleft, unwinding of promoter DNA, transcription elongation complex stability, transcription pausing, and transcription termination. Crystal structures and single-molecule FRET studies establish that the clamp can adopt open and closed conformational states; however, the occurrence, pathway, and kinetics of transitions between clamp states have been unclear. Using single-molecule FRET (smFRET) on surface-immobilized RNAP molecules, we show that the clamp in RNAP holoenzyme exists in three distinct conformational states: the previously defined open state, the previously defined closed state, and a previously undefined partly closed state. smFRET time-traces show dynamic transitions between open, partly closed, and closed states on the 0.1-1 second time-scale. Similar analyses of transcription initiation complexes confirm that the RNAP clamp is closed in the catalytically competent transcription initiation complex and in initial transcribing complexes (RPITC), including paused initial transcribing complexes, and show that, in these complexes, in contrast to in RNAP holoenzyme, the clamp does not interconvert between the closed state and other states. The stringent-response alarmone ppGpp selectively stabilizes the partly-closed-clamp state, inhibiting interconversion between the partly closed state and the open state. The methods of this report should allow elucidation of clamp conformation and dynamics during all phases of transcription.

SIGNIFICANCE STATEMENT

The clamp forms a pincer of the RNA polymerase “crab-claw” structure, and adopts many conformations with poorly understood function and dynamics. By measuring distances within single surface-attached molecules, we observe directly the motions of the clamp and show that it adopts an open, a closed, and a partly closed state; the last state is stabilized by a sensor of bacterial starvation, linking the clamp conformation to the mechanisms used by bacteria to counteract stress. We also show that the clamp remains closed in many transcription steps, as well as in the presence of a specific antibiotic. Our approach can monitor clamp motions throughout transcription and offers insight on how antibiotics can stop pathogens by blocking their RNA polymerase movements.
The TRPC6-AMPK pathway is involved in cytoskeleton reorganization and glucose uptake in podocytes
Authors: Rachubik Patrycja , Szrejder Maria , Rogacka Dorota , Audzeyenka Irena , Rychłowski Michał , Angielski Stefan , Piwkowska Agnieszka
Published: March 2018

Podocytes are dynamic polarized cells on the surface of glomerular capillaries that are an essential part of the glomerular filtration barrier. AMP-activated protein kinase (AMPK), a key regulator of glucose and fatty acid metabolism, plays a major role in obesity and type 2 diabetes. Accumulating evidence suggests that TRPC6 channels are crucial mediators of calcium transport in podocytes and are involved in regulating glomerular filtration barrier. Here we investigated whether the AMPK-TRPC6 pathway is involved in insulin-dependent cytoskeleton reorganization and glucose uptake in cultured rat podocytes. Insulin regulates the interaction of TRPC6 with AMPKα2 in cultured rat podocytes The results suggested a key role for the TRPC6 channel in the mediation of insulin-dependent activation of AMPKα2, actin cytoskeleton reorganization and glucose uptake in podocyte. Moreover, AMPK and TRPC6 activation were required to stimulate the Rac1 signaling pathway. These results suggest a potentially important new mechanism that regulates glucose transport in podocytes and that could be injurious during diabetes.
Expansion stimulated emission depletion microscopy (ExSTED)
Authors: Gao Mengfei , Maraspini Riccardo , Beutel Oliver , Zehtabian Amin , Eickholt Britta , Honigmann Alf , Ewers Helge
Published: March 2018

Stimulated emission depletion (STED) microscopy is routinely used to resolve the ultra-structure of cells with a ∼10-fold higher resolution compared to diffraction limited imaging. While STED microscopy is based on preparing the excited state of fluorescent probes with light, the recently developed expansion microscopy (ExM) provides sub-diffraction resolution by physically enlarging the sample before microscopy. Expansion of fixed cells by crosslinking and swelling of hydrogels easily enlarges the sample ∼4-fold and hence increases the effective optical resolution by this factor. To overcome the current limits of these complimentary approaches, we here combined ExM with STED (ExSTED) and demonstrate an increase in resolution of up to 30-fold compared to conventional microscopy (<10 nm lateral and ∼50 nm isotropic). While the increase in resolution is straight forward, we found that high fidelity labelling via multi-epitopes is required to obtain emitter densities that allow to resolve ultra-structural details with ExSTED. Our work provides a robust template for super resolution microscopy of entire cells in the ten nanometer range.
Volvox barberi flocks, forming near-optimal, two-dimensional, polydisperse lattice packings
Authors: Balasubramanian Ravi Nicholas
Published: March 2018

Volvox barberi is a multicellular green alga forming spherical colonies of 10000-50000 differentiated somatic and germ cells. Here, I show that these colonies actively self-organize over minutes into “flocks” that can contain more than 100 colonies moving and rotating collectively for hours. The colonies in flocks form two-dimensional, irregular, “active crystals”, with lattice angles and colony diameters both following log-normal distributions. Comparison with a dynamical simulation of soft spheres with diameters matched to the Volvox samples, and a weak long-range attractive force, show that the Volvox flocks achieve optimal random close-packing. A dye tracer in the Volvox medium revealed large hydrodynamic vortices generated by colony and flock rotations, providing a likely source of the forces leading to flocking and optimal packing.
Quantifying the impact of a periodic presence of antimicrobial on resistance evolution in a homogeneous microbial population of fixed size
Authors: Marrec Loïc , Bitbol Anne-Florence
Published: March 2018

The evolution of antimicrobial resistance often occurs in a variable environment, as antimicrobial is given periodically to a patient or added and removed from a medium. This environmental variability has a huge impact on the microorganisms’ fitness landscape, and thus on the evolution of resistance. Indeed, mutations conferring resistance often carry a fitness cost in the absence of antimicrobial, which may be compensated by subsequent mutations. As antimicrobial is added or removed, the relevant fitness landscape thus switches from a fitness valley to an ascending landscape or vice-versa.

Here, we investigate the effect of these time-varying patterns of selection within a stochastic model. We focus on a homogeneous microbial population of fixed size subjected to a periodic alternation of phases of absence and presence of an antimicrobial that stops growth. Combining analytical approaches and stochastic simulations, we quantify how the time necessary for fit resistant bacteria to take over the microbial population depends on the period of the alternations. We demonstrate that fast alternations strongly accelerate the evolution of resistance, and that a plateau is reached once the period gets sufficiently small. Besides, the acceleration of resistance evolution is stronger for larger populations. For asymmetric alternations, featuring a different duration of the phases with and without antimicrobial, we shed light on the existence of a broad minimum of the time taken by the population to fully evolve resistance. At this minimum, if the alternations are sufficiently fast, the very first resistant mutant that appears ultimately leads to full resistance evolution within the population. This dramatic acceleration of the evolution of antimicrobial resistance likely occurs in realistic situations, and can have an important impact both in clinical and experimental situations.
OMCD: OncoMir Cancer Database
Authors: Sarver Aaron , Sarver Anne , Yuan Ce , Subramanian Subbaya
Published: March 2018

MicroRNAs (miRNAs) are crucially important in the development of cancer. Their dysregulation, commonly observed in various types of cancer, is largely cancer-dependent. Thus, to understand the tumor biology and to develop accurate and sensitive biomarkers, we need to understand pan-cancer miRNA expression. At the University of Minnesota, we developed the OncoMir Cancer Database (OMCD), hosted on a web server, which allows easy and systematic comparative genomic analyses of miRNA sequencing data derived from more than 9,500 cancer patients tissue samples available in the Cancer Genome Atlas (TCGA). OMCD includes associated clinical information and is searchable by organ-specific terms common to the TCGA. Freely available to all users (www.oncomir.umn.edu/omcd/), OMCD enables (1) simple visualization of TCGA miRNA sequencing data, (2) statistical analysis of differentially expressed miRNAs for each cancer type, and (3) exploration of miRNA clusters across cancer types.

Database URL

www.oncomir.umn.edu/omcd
Organ-specific translation elongation rates measured by in vivo ribosome profiling
Authors: Gerashchenko Maxim V. , Peterfi Zalan , Gladyshev Vadim N.
Published: March 2018

Protein synthesis and degradation are intricate biological processes involving more than a hundred proteins operating in a highly orches-trated fashion. Despite the progress, few options are available to access translation in live animals as the increase in animal’s complexity limits the repertoire of experimental tools that could be applied to observe and manipulate processes within animal’s body, organs, and individual cells. It this study, we developed a labeling-free method for measuring organ- and cell-type specific translation elongation rates. It is based on a time-resolved delivery of translation initiation and elongation inhibitors in live animals followed by ribosome profiling. It also reports translation initiation sites in an organ-specific manner. Using this method, we found that the elongation rates differ among mouse organs and determined them to be 6.8, 5.2, and 4.4 amino acids per sec for liver, kidney, and skeletal muscle, respectively.

Significance

Protein synthesis is a vital biological process. Modern methods of genome editing enable generation of sophisticated animal models to study the regulation of protein synthesis in health end disease. However, the methods that could track various steps of translation at a gene level resolutionin vivoare lacking, particularly in complex vertebrates, such as mice and rats. Here, we measured the translation elongation rate in several organs by delivering inhibitors specific to certain phases of translation directly through the mouse bloodstream. This study lays out a path for interrogating translation in animals in response to various genetic and dietary interventions.
Effect of counter-ion on packing and crystal density of 5,5′-(3,3′-bi[1,2,4-oxadiazole]-5,5′-diyl)bis(1H-tetrazol-1-olate) with five different cations
Authors: Giles Ian D. , DeHope Alan J. , Zuckerman Nathaniel B. , Parrish Damon A. , Pagoria Philip F.
Published: March 2018

In energetic materials, the crystal density is an important parameter that affects the performance of the material. When making ionic energetic materials, the choice of counter-ion can have detrimental or beneficial effects on the packing, and therefore the density, of the resulting energetic crystal. Presented herein are a series of five ionic energetic crystals, all containing the dianion 5,5′-(3,3′-bi[1,2,4-oxadiazole]-5,5′-diyl)bis(1H-tetrazol-1-olate), with the following cations: hydrazinium (1) (2N2H5
+·C6N12O4
2−), hydroxylammonium (2) 2NH4O+·C6N12O4
2− [Pagoria et al.. (2017). Chem. Heterocycl. Compd, 53, 760–778; included for comparison], dimethylammonium (3) (2C2H8N+·C6N12O4
2−), 5-amino-1H-tetrazol-4-ium (4) (2CH4N5
+·C6N12O4
2−·4H2O), and aminoguanidinium (5) (2CH7N4
+·C6N12O4
2−). Both the supramolecular interactions and the sterics of the cation play a role in the density of the resulting crystals, which range from 1.544 to 1.873 Mg m−1. In 5, the tetrazolate ring is disordered over two positions [occupancy ratio 0.907 (5):0.093 (5)] due to a 180° rotation in the terminal tetrazole rings.
Naloxegol hydrogen oxalate displaying a hydrogen-bonded layer structure
Authors: Gelbrich Thomas , Langes Christoph , Stefinovic Marijan , Griesser Ulrich J.
Published: March 2018

In the salt (5α,6α)-6-[(2,5,8,11,14,17,20-heptaoxadocosan-22-yl)oxy]-3,14-dihydroxy-17-(prop-2-en-1-yl)-4,5-epoxymorphinan-17-ium hydrogen oxalate, C34H54NO11
+·C2HO4
− the polyether unit of the naloxegol cation adopts the shape of a squashed open letter `O'. In the crystal, the hydrogen oxalate anions are linked into a chain by O—H...O hydrogen bonds. Each naloxegol unit is hydrogen bonded to three hydrogen oxalate ions via two O—H...O and one N—H...O interactions. The resulting hydrogen-bonded two-dimensional layer structure is 3,5-connected and has the 3,5 L50 topology.
Crystal structure of Dehydrodieugenol B methyl ether, a neolignan from Nectandra leucantha Nees and Mart (Lauraceae)
Authors: Grecco Simone S. , Jerz Gerold , Lago Joao Henrique G. , Jones Peter G.
Published: March 2018

In the title compound, C21H24O4 (systematic name: 4,5′-diallyl-2,2′,3′-trimethoxydiphenyl ether), the aromatic rings lie almost perpendicular to each other [dihedral angle = 85.96 (2)°]. The allyl side chains show similar configurations, with Car—C—C=C (ar = aromatic) torsion angles of −123.62 (12) and −115.54 (12)°. A possible weak intramolecular C—H...O interaction is observed. In the crystal, molecules are connected by two C—H...O hydrogen bonds, forming undulating layers lying parallel to the bc plane. Weak C—H...π and π–π stacking interactions also occur.
(E)-1,3-Bis(anthracen-9-yl)prop-2-en-1-one: crystal structure and DFT study
Authors: Zainuri Dian Alwani , Razak Ibrahim Abdul , Arshad Suhana
Published: March 2018

The title compound, C31H20O, was synthesized using a Claisen–Schmidt condensation. The enone group adopts an s-trans conformation and the anthracene ring systems are twisted at angles of 85.21 (19) and 83.98 (19)° from the enone plane. In the crystal, molecules are connected into chains along [100] via weak C—H...π interactions. The observed band gap of 3.03 eV is in excellent agreement with that (3.07 eV) calculated using density functional theory (DFT) at the B3LYP/6–311++G(d,p) level. The Hirshfeld surface analysis indicates a high percentage of C...H/H...C (41.2%) contacts in the crystal.
1-Deoxy-1-(N-methyl-4-fluorophenylamino)-D-arabino-hexulose
Authors: Mossine Valeri V. , Barnes Charles L. , Mawhinney Thomas P.
Published: March 2018

The title compound, C13H18FNO5, consists of D-fructose with an aromatic amine. The carbohydrate chain is in the acyclic keto form and has the zigzag conformation, while the solid-state NMR data suggests a conformational dimorphism at the aromatic amine group. The carbohydrate portion is involved in extensive O—H...O hydrogen bonding, which forms a two-dimensional network parallel to (001) and organized into fused homodromic ring patterns. The Hirshfeld surface fingerprint plots reveal a major contribution of the non-polar H...H and C...H interactions to the crystal packing forces.
Does subsidized MPCI crowds out traditional market-based hail insurance in the Netherlands?
Authors: van Asseldonk Marcel , van der Meulen Harold , van der Meer Ruud , Silvis Huib , Berkhout Petra
Published: March 2018

Purpose

The purpose of this paper is to determine which factors influence the choice to adopt subsidized multi-peril crop insurance (MPCI) in the Netherlands and whether prior hail insurance uptake is one of the determinants of MPCI adoption. In addition, it is analyzed whether subsidized MPCI has reduced disaster relief spending.

Design/methodology/approach

Cross-sectional survey with 512 respondents using a stratified design comprising MPCI adopters and non-adopters sampled from the Dutch national census data base. The national census, including information on subsidized MPCI adoption from 2010 up to and including 2015, was supplemented with information on (prior) traditional market-based hail insurance uptake, and other underlying determining factors were elicited. Logistic regression analysis was used to determine which factors influence the choice to adopt MPCI.

Findings

Analysis of MPCI adoption reveals that subsidized MPCI mainly substituted for market-based hail insurance uptake up to now. Growers who did not insure against hail in the past were hardly reached. Approximately, three-quarter of MPCI adopters insured hail prior to market introduction of MPCI. In the arable sector, MPCI adoption was 2.89 (p<0.01) more likely for prior hail insurance adopters compared to non-adopters, while it was 9.67 (p<0.01) more likely in the fruit sector.

Research limitations/implications

In the arable sector, it is expected that MPCI uptake in the coming years will reach more prior non-adopters of hail insurance as demand is expected to increase. Prior hail insurance adopters in the arable sector can be seen as the early MPCI adopters. In the fruit sector, adoption rates are already at a relative high level and a further significant increase by targeting non-adopters of hail insurance is not likely.

Originality/value

Governmental support has crowded out to some extend traditional market-based hail insurance in the Netherlands. Since the Common Agricultural Policy of the European Union is creating more momentum to subsidize crop insurance more member states with a long history of a mature hail insurance market may be confronted with similar crowding-out effects.
Experiences of visitors to Gallipoli, a nostalgia-themed dark tourism destination: an insight from TripAdvisor
Authors: Çakar Kadir
Published: March 2018

Purpose

The purpose of this paper is to examine and understand the experiences of travelers to Gallipoli, by analyzing their online comments and reviews.

Design/methodology/approach

The data were garnered from the well-known online user blog TripAdvisor. Data, concerning visiting the Gallipoli Peninsula, were retrieved from (n=330) travelers’ reviews and comments, and were examined using content analysis to elicit and identify their experiences.

Findings

Overall, the travelers’ reviews and comments mostly conveyed emotional and nostalgic experiences. Further, the travelers’ nostalgic experiences of Gallipoli emerged as historical nostalgia deriving from the personal attachment of travelers to the site.

Research limitations/implications

The data have shown that the experiences of travelers to Gallipoli can mostly be identified as emotional, which are generally consistent with the current literature. This paper utilized traveler reviews and comments on TripAdvisor, left by tourists who had previously visited Gallipoli, and this represents the limitation of the present study. Thus, to better understand the experiences of travelers visiting Gallipoli, with regard to their psychological aspect, future research should be conducted with travelers either through face-to-face interviews or via a survey.

Originality/value

Despite its significance for dark tourists, limited research has been carried out that deals with the experiences of travelers visiting the Gallipoli battlefield. As such, this is the first research project designed to highlight the experience of dark tourism, under the concept of nostalgic tourism, by providing valuable data and a deeper understanding of the field.
Exploring entrepreneurial intention’s mediating role in the relationship between self-efficacy and nascent behaviour
Authors: Mwiya Bruce M.K. , Wang Yong , Kaulungombe Bernadette , Kayekesi Maidah
Published: March 2018

Purpose

The purpose of this paper is to examine the mediating role of entrepreneurial intention (EI) in relation to the influence of the five dimensions of entrepreneurial self-efficacy (ESE) on nascent behaviour.

Design/methodology/approach

The study relies on a quantitative approach where primary data were collected from 294 final year undergraduate students at a public university in Zambia. The data were examined by using correlation, logistic regression and mediation analyses.

Findings

The findings indicate that each of the five dimensions of ESE is positively and significantly related with EI. Additionally, each of the ESE dimensions, except the financial aspect, is positively correlated with nascent behaviour. Finally, the results show that the influence of ESE dimensions on nascent behaviour is significantly mediated by intention.

Research limitations/implications

The study took place in a public university in Zambia; more universities could be involved to improve the generalisability of the study conclusions.

Practical implications

The study shows that the five ESE dimensions positively influence not only business start-up intention but also nascent behaviour. To motivate graduates’ involvement in business start-up, there is a need to tailor training and practical pedagogical approaches on entrepreneurship that are focussed on developing the five ESE dimensions.

Originality/value

This paper extends an emerging body of knowledge which has not been fully investigated in terms of the mediating role of intention on the relationships between dimensions of ESE and nascent behaviour. The study also makes a valuable contribution to the under-researched context of Zambia and African entrepreneurship.
Enigma of successful new technology utilization by auto parts MSMEs in northern India
Authors: Singh Jagdeep , Singh Harpuneet
Published: March 2018

Purpose

The purpose of this study is to discover the elements that affect the new technology utilization by auto parts’ micro-, small- and medium-sized enterprises (MSMEs) in northern India.

Design/methodology/approach

Based on the literature and professional reviews, 75 critical factors were identified on the basis of that affecting technology utilization in the auto parts-manufacturing MSMEs in Punjab. A survey was conducted in 113 auto parts industries (MSMEs) in Punjab. Descriptive statistics and factors analysis (principle component analysis) in SPSS software was used to examine the data.

Findings

After the analysis, 56 prominent factors were presented those are affecting the technology utilization in auto parts industry. After the study, 23 factors were identified, which explains the variance of 74.99 per cent of the total data. Most important factors for new technology utilization in MSMEs in Punjab are proper understanding of current operation and availability of professional consultant, problems with the compatibility of equipment and fear of layoffs, and the least important factors are volume flexibility and maintenance expenses.

Research limitations/implications

These results deliver valuable perceptions into the awareness of by what means technology utilization has taken place in MSMEs.

Practical implications

The present work delivers beneficial strategies to MSMEs facing ups and downs because of their industry atmosphere.

Originality/value

This research adds to the literature on technology utilization and aids MSMEs in improving themselves for the excursion ahead.
Notes on pollination ecology and floral scent chemistry of the rare neotropical orchid Catasetum galeritumRchb.f.
Authors: Milet‐Pinheiro Paulo , Silva João Batista F. , Navarro Daniela M.A.F. , Machado Isabel C.S. , Gerlach Günter
Published: March 2018

The neotropical orchid genus Catasetum embraces about 180 species that produce perfume as reward for pollinators (i.e. male euglossine bees). Among the ca. 1000 perfume‐rewarding plants, Catasetum species are the best studied with respect to their natural history. Nevertheless, the pollination ecology of most species (> 80%) remains unknown. Here, we investigated the pollination ecology and floral scent chemistry of C. galeritum, a rare species endemic to the poorly investigated Brazilian Amazon. Flowers of C. galeritum were visited only by male bees of Eufriesea superba. Its perfume bouquet was composed of six volatiles, with 1,4‐dimethoxybenzene accounting for about 85% of the total scent discharge. Curiously, this compound is a potent attractant of more than 40 euglossine species. The absence of euglossine species other than Ef. superba on flowers of C. galeritum might be, therefore, be mediated by a modifier effect of another compound(s) in its floral scent bouquet.
Primer selection impacts specific population abundances but not community dynamics in a monthly time‐series 16S rRNA gene amplicon analysis of coastal marine bacterioplankton
Authors: Wear Emma K. , Wilbanks Elizabeth G. , Nelson Craig E. , Carlson Craig A.
Published: March 2018

Primers targeting the 16S small subunit ribosomal RNA marker gene, used to characterize bacterial and archaeal communities, have recently been re‐evaluated for marine planktonic habitats. To investigate whether primer selection affects the ecological interpretation of bacterioplankton populations and community dynamics, amplicon sequencing with four primer sets targeting several hypervariable regions of the 16S rRNA gene was conducted on both mock communities constructed from cloned 16S rRNA genes and a time‐series of DNA samples from the temperate coastal Santa Barbara Channel. Ecological interpretations of community structure (delineation of depth and seasonality, correlations with environmental factors) were similar across primer sets, while population dynamics varied. We observed substantial differences in relative abundances of taxa known to be poorly resolved by some primer sets, such as Thaumarchaeota and SAR11, and unexpected taxa including Roseobacter clades. Though the magnitude of relative abundances of common OTUs differed between primer sets, the relative abundances of the OTUs were nonetheless strongly correlated. We do not endorse one primer set but rather enumerate strengths and weaknesses to facilitate selection appropriate to a system or experimental goal. While 16S rRNA gene primer bias suggests caution in assessing quantitative population dynamics, community dynamics appear robust across studies using different primers.
The ecological genetics of Pseudomonas syringae from kiwifruit leaves
Authors: Straub Christina , Colombi Elena , Li Li , Huang Hongwen , Templeton Matthew D. , McCann Honour C. , Rainey Paul B.
Published: March 2018

Interactions between commensal microbes and invading pathogens are understudied, despite their likely effects on pathogen population structure and infection processes. We describe the population structure and genetic diversity of a broad range of co‐occurring Pseudomonas syringae isolated from infected and uninfected kiwifruit during an outbreak of bleeding canker disease caused by P. syringae pv. actinidiae (Psa) in New Zealand. Overall population structure was clonal and affected by ecological factors including infection status and cultivar. Most isolates are members of a new clade in phylogroup 3 (PG3a), also present on kiwifruit leaves in China and Japan. Stability of the polymorphism between pathogenic Psa and commensal P. syringae PG3a isolated from the same leaf was tested using reciprocal invasion from rare assays in vitro and in planta. P. syringae G33C (PG3a) inhibited Psa NZ54, while the presence of Psa NZ54 enhanced the growth of P. syringae G33C. This effect could not be attributed to virulence activity encoded by the Type 3 secretion system of Psa. Together our data contribute toward the development of an ecological perspective on the genetic structure of pathogen populations.
Nutrient factories: metabolic function of beneficial microorganisms associated with insects
Authors: Ankrah Nana Y. D. , Douglas Angela E.
Published: March 2018

Many symbiotic microorganisms in animals, including insects, have parallels to microbial nutrient factories of biotechnology: just as the metabolism of individual microorganisms and microbial communities is modified by biotechnologists to produce specific nutrients, so the many insect‐associated microorganisms synthesize specific nutrients that support the sustained growth and reproduction of their animal host. Three broad metabolic functions are mediated by insect‐associated microorganisms: (i) fermentation of dietary constituents, releasing products that contribute to host carbon and energy metabolism; (ii) overproduction of nutrients, notably essential amino acids, required by the host and (iii) recycling of host waste metabolites. In many systems, the nutrients that are released from living microbial cells have been identified, with evidence for metabolite cross‐feeding and shared metabolic pathways both among different microbial taxa and between microorganisms and the host. However, the flux of nutrients from microbial cells to host has rarely been quantified; our understanding of the processes that regulate nutrient transfer is fragmentary; and the scale and mechanism of metabolic adaptations of microorganisms to host nutritional demand are largely unknown. Recent advances in metabolic, microscopical and modelling techniques offer excellent opportunities to resolve these outstanding issues, with insights that can contribute to the effective design of nutrient factories for biotechnological applications.
From the Wembley Conference to the ‘McDonnell Amendment’: Labour's Leadership Nomination Rules
Authors: Quinn Tom
Published: March 2018

A recent change to the Labour party's nomination rules for leadership elections was the eighth such major modification of this brief clause in the party's rule book since 1981. These changes have provided a barometer of factional conflict over this period and indicate the importance of gate‐keeping powers in leadership selection. This article recounts the history of these eight rule changes. It shows how the proportion of Labour MPs (and later MEPs) required to nominate candidates in leadership elections has oscillated markedly, as the left has tried to reduce it while centrists have sought to increase it. The most recent change in 2017, when the threshold was decreased to 10 per cent of Labour MPs and MEPs, was a victory for the left. The article argues that the changes to Labour's nomination rules, while lower‐key than the extension of voting rights from MPs to ordinary members, have been just as significant.
Pricing Lives: International Guideposts for Safety
Authors: Viscusi W. Kip
Published: March 2018

Government agencies throughout the world use the value of a statistical life (VSL) to monetise the mortality risk reduction benefits of government policies. The most reliable empirical estimates of the VSL using US labour market data are about US$10 million (year 2015 US dollars). Based on international estimates of the income elasticity of the VSL, one can transfer these values to other countries, leading to my VSL estimate for Australia of US$7.9 million, or A$10.0 million, which is over double the current Australia best‐practices value. Transferring US VSL estimates to other nations after accounting for income differences will boost global VSL estimates. Potential refinements of the VSL based on age and income are also feasible. The VSL could serve a pivotal role in promoting safety by valuing lives in litigation contexts, regulatory sanctions, and corporate risk analyses.
Does respiratory variation of inferior vena cava diameter predict fluid responsiveness in spontaneously ventilating children with sepsis
Authors: Long Elliot , Duke Trevor , Oakley Ed , O'Brien Adam , Sheridan Bennett , Babl Franz E ,   on behalf of the Pediatric Research in Emergency Departments International Collaborative (PREDICT)
Published: March 2018

Objective

The intent of fluid bolus therapy (FBT) is to increase cardiac output and tissue perfusion, yet only 50% of septic children are fluid responsive. We evaluated respiratory variation of inferior vena cava (IVC) diameter as a predictor of fluid responsiveness.

Methods

A prospective observational study in the ED of The Royal Children's Hospital, Melbourne, Australia. Patients were spontaneously ventilating children treated with FBT for sepsis‐induced acute circulatory failure. IVC ultrasound was performed prior to FBT. Trans‐thoracic echocardiography was performed prior to, 5 and 60 min after FBT. IVC collapsibility index and stroke distance were calculated by a blinded Paediatric Emergency Physician and blinded Paediatric Cardiologist, respectively.

Results

Thirty‐nine fluid boluses were recorded in 33 children, 28/39 (72%) of which met criteria for fluid responsiveness at 5 min, which was sustained in 2/28 (7%) of initial fluid responders at 60 min. Sensitivity and specificity (95% confidence interval) of IVC collapsibility index were 0.44 (0.25–0.65) and 0.33 (0.10–0.65) with an area under the receiver operator characteristics curve (95% confidence interval) of 0.38 (0.23–0.55) at 5 min. Test characteristics 60 min after fluid bolus administration were not meaningful because of the infrequency of sustained fluid responsiveness in this patient group. There was no significant correlation between IVC collapsibility and fluid responsiveness at 5 or 60 min.

Conclusions

IVC collapsibility has poor test characteristics for predicting fluid responsiveness in spontaneously ventilating children with sepsis.
Predictors of weight reduction and maintenance in a large cohort of overweight and obese adults in a community setting
Authors: Bachar Adina , Livshits Gregory , Birk Ruth
Published: March 2018

Aim

In overweight/obese individuals, modest 5% weight loss and its maintenance promotes health; however, it is challenging and typically unachievable, especially in community settings. Established predictors of weight loss outcome in a community setting are lacking, hindering the development of practical interventions and prevention tools. Our aim was to identify predictors associated with 5% weight reduction (initial 6 months) and maintenance (1 year) in overweight and obese adults undergoing weight reduction treatment, free of charge, in a community setting.

Methods

Computerised medical files of 11 842 adults aged 50.6 ± 16.3 years, attending 162 primary clinics, were analysed retrospectively. Thirty medical, biochemical and demographic independent variables were tested as potential predictors using multiple logistic regression models.

Results

Significant predictors of high successful weight reduction were: not being treated with insulin (odds ratio (OR) = 0.53), higher baseline body mass index (OR = 1.05) and younger age (OR = 0.98). Weight maintenance predictors were: successful initial weight reduction (OR = 1.26), short time intervals between weighings (OR = 0.88) and frequent weighing (OR = 0.95). Visits to a dietitian were significantly associated with success during both periods: each visit raised the probability of success by 13.4 and 7.6%, respectively. Type 2 diabetes or use of hypoglycaemic drugs were not significant predictors.

Conclusions

In a community‐based setting, number of visits to a dietitian is a strong predictor of successful weight reduction and maintenance. Initial success is a critical predictor of weight loss maintenance. Subgroup of older, diabetic patients treated with insulin has a dramatically lower probability of weight reduction success.
Loan Sales and Borrowers’ Accounting Conservatism
Authors: Deng Saiying , Li Yutao , Lobo Gerald J. , Shao Pei
Published: March 2018

We examine whether initial loan sales in the secondary loan market relate to borrowing firms’ accounting conservatism. We find that borrowing firms exhibit a significant decline in accounting conservatism after the initial loan sales. We show that the decline in borrower conservatism is more pronounced for firms that borrow from lenders with lower monitoring incentives and for firms that have lower incentives to supply conservatism. The baseline results are robust to a battery of sensitivity tests. Collectively, we provide corroborative evidence that lead lenders’ monitoring incentives enforce accounting conservatism in the private debt market, and that lead lenders play a more prominent role than secondary loan market participants in shaping corporate (conservative) reporting.
Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx
Authors: Tranberg A. , Thorarinsdottir H. R. , Holmberg A. , Schött U. , Klarin B.
Published: March 2018

Background

The normal body exists in mutualistic balance with a large range of microbiota. The primary goal of this study was to establish whether there is an imbalance in the oropharyngeal flora early after hospital or ICU admittance, and whether flora differs between control, ward and critically ill patients. The secondary goal was to explore whether there are patient characteristics that can be associated with a disturbed oropharyngeal flora.

Methods

Oropharyngeal cultures were obtained from three different study groups: (1) controls from the community, (2) ward patients and (3) critically ill patients, the two latter within 24 h after admittance.

Results

Cultures were obtained from 487 individuals: 77 controls, 193 ward patients and 217 critically ill patients. Abnormal pharyngeal flora was more frequent in critically ill and ward patients compared with controls (62.2% and 10.4% vs. 1.3%, P < 0.001 and P = 0.010, respectively). Colonisation of gut flora in the oropharynx was more frequent in critically ill patients compared with ward patients or controls (26.3% vs. 4.7% and 1.3%, P < 0.001 and P < 0.001, respectively). Proton pump inhibitor medication was the strongest independent factor associated with the presence of gut flora in the oropharynx in both ward and critically ill patients (P = 0.030 and P = 0.044, respectively).

Conclusion

This study indicates that abnormal oropharyngeal flora is an early and frequent event in hospitalised patients and more so in the critically ill, compared to controls. Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx.
Microanatomy of the digestive tract, hooves and some visceral organs of addax antelope (Addax nasomaculatus) following a concentrate or forage feeding regime
Authors: Tahas S. A. , Hetzel U. , Altenbrunner‐Martinek B. , Martin Jurado O. , Hammer S. , Arif A. , Hatt J.‐M. , Clauss M.
Published: March 2018

Subacute ruminal acidosis is a common disease in captive non‐domesticated ruminants and is mainly diagnosed by rumen fluid pH and rumen histology. Furthermore, differences in ruminant gastrointestinal histology have been hypothesized to correlate with the browser–grazer continuum. Twelve surplus addax antelope (Addax nasomaculatus) were divided into two groups, fed either their usual diet, consisting of a concentrate feed with a limited amount of hay, or a diet of unlimited hay only, for 3 months. After culling, descriptive and morphometric histology and pH measurements were compared between groups. Significant variations in cellular subpopulations were noted between groups, with roughage‐fed individuals presenting primarily with balloon cells of the Stratum corneum and living layer cell vacuolization, whereas parakeratosis and intermediate‐type cells were more frequent in the concentrate‐fed group. Lesions typical of subacute ruminal acidosis were significantly more pronounced in concentrate‐fed individuals. Ruminal pH measurements did not differ significantly, but were more consistent in forage‐fed individuals, indicating a more stable reticuloruminal environment. The results indicate that ruminal histology may be more appropriate in assessing ruminal health compared to a single post‐mortem pH measurement. It is proposed that Stratum corneum balloon cells may indicate cell maturation and not, as previously assumed, hyperfunction. Concentrate‐fed individuals scored higher on the presence of inflammatory cells on hoof corium histology. The study further emphasizes the adaptability of ruminant digestive tract microanatomy in adult animals even after a short period of time and the positive effects an increased roughage diet may have in populations of captive grazing ruminants.
Genetic relatedness of indigenous ethnic groups in northern Borneo to neighboring populations from Southeast Asia, as inferred from genome‐wide SNP data
Authors: Yew Chee Wei , Hoque Mohd Zahirul , Pugh‐Kitingan Jacqueline , Minsong Alexander , Voo Christopher Lok Yung , Ransangan Julian , Lau Sophia Tiek Ying , Wang Xu , Saw Woei Yuh , Ong Rick Twee‐Hee , Teo Yik‐Ying , Xu Shuhua , Hoh Boon‐Peng , Phipps Maude E. , Kumar S. Vijay
Published: March 2018

The region of northern Borneo is home to the current state of Sabah, Malaysia. It is located closest to the southern Philippine islands and may have served as a viaduct for ancient human migration onto or off of Borneo Island. In this study, five indigenous ethnic groups from Sabah were subjected to genome‐wide SNP genotyping. These individuals represent the “North Borneo”‐speaking group of the great Austronesian family. They have traditionally resided in the inland region of Sabah. The dataset was merged with public datasets, and the genetic relatedness of these groups to neighboring populations from the islands of Southeast Asia, mainland Southeast Asia and southern China was inferred. Genetic structure analysis revealed that these groups formed a genetic cluster that was independent of the clusters of neighboring populations. Additionally, these groups exhibited near‐absolute proportions of a genetic component that is also common among Austronesians from Taiwan and the Philippines. They showed no genetic admixture with Austro‐Melanesian populations. Furthermore, phylogenetic analysis showed that they are closely related to non–Austro‐Melansian Filipinos as well as to Taiwan natives but are distantly related to populations from mainland Southeast Asia. Relatively lower heterozygosity and higher pairwise genetic differentiation index (FST) values than those of nearby populations indicate that these groups might have experienced genetic drift in the past, resulting in their differentiation from other Austronesians. Subsequent formal testing suggested that these populations have received no gene flow from neighboring populations. Taken together, these results imply that the indigenous ethnic groups of northern Borneo shared a common ancestor with Taiwan natives and non–Austro‐Melanesian Filipinos and then isolated themselves on the inland of Sabah. This isolation presumably led to no admixture with other populations, and these individuals therefore underwent strong genetic differentiation. This report contributes to addressing the paucity of genetic data on representatives from this strategic region of ancient human migration event(s).
A novel IKBKG mutation in a patient with incontinentia pigmenti and features of hepatic ciliopathy
Authors: Danescu Sorina , Has Cristina , Baican Corina , Müller Thomas , Baican Adrian
Published: March 2018

We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor‐kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.
Maternal cytomegalovirus sero‐positivity and autism symptoms in children
Authors: Slawinski Brooke L. , Talge Nicole , Ingersoll Brooke , Smith Arianna , Glazier Alicynne , Kerver Jean , Paneth Nigel , Racicot Karen
Published: March 2018

Problem

Autism spectrum disorder (ASD) is one of the most commonly diagnosed neurodevelopmental disorders in the United States. While ASD can be significantly influenced by genetics, prenatal exposure to maternal infections has also been implicated in conferring risk. Despite this, the effects of several important maternal pathogens, such as cytomegalovirus (CMV) and herpes simplex virus 2 (HSV2), remain unknown.

Method of study

We tested whether maternal CMV and/or HSV2 sero‐positivity was associated with ASD symptoms in children. ELISA was used to assay for CMV IgG and HSV2 IgG in serum from the mothers of 82 children whose ASD symptoms were assessed at 3‐6 years of age using the Social Responsiveness Scale version 2 (SRS‐2).

Results

Associations between maternal viral serostatus and SRS‐2 scores were estimated using linear regression with covariate adjustments. The children of mothers sero‐positive for CMV, but not for HSV2, had SRS‐2 scores 3.6‐4.2 points higher, depending on the adjustment model, than sero‐negative women, a significant finding, robust to several statistical adjustments.

Conclusion

Our results suggest that maternal CMV infections may influence ASD symptoms. These findings are being further evaluated in ongoing prospective studies with larger population samples.
Surgical versus non‐surgical management of type B ankle fractures with minimal talar shift in adults: a systematic review
Authors: Mittal Rajat , Drynan David , Harris Ian A. , Naylor Justine M.
Published: March 2018

Background

This systematic review aims to determine the effectiveness of surgical and non‐surgical management for the type B ankle fracture with minimal talar shift.

Methods

Two authors independently systematically searched the following databases: MEDLINE, EMBASE and CENTRAL. Only randomized controlled trials were included that evaluated surgical versus non‐surgical management of type B ankle fracture with minimal talar shift in adults. Two authors independently performed study selection, risk of bias assessment and data extraction. Main outcomes extracted were general health and ankle function. Heterogeneity was assessed using I2 and chi‐squared statistic. Data were pooled using fixed effect where appropriate.

Results

Two studies were included involving 241 patients. The pooled mean difference for the physical component score was 0.60 (95% confidence interval (CI): −1.62 to 2.82) non‐significantly favouring surgical management. One study reported no significant difference in ankle function (mean difference: 3.20; 95% CI: −6.56 to 12.96) whilst the other reported a significant difference favouring non‐surgical management (mean difference: 3.20; 95% CI: 0.44–5.96). Ankle function scores were not pooled due to heterogeneity. Meta‐analysis showed that the surgical group was more likely to develop a minor infection (odds ratio: 12.46; 95% CI: 2.29–67.78) or undergo hardware removal (odds ratio: 4.40; 95% CI: 1.09–17.84). There was no significant difference in major infection between the two groups (odds ratio: 4.03; 95% CI: 0.44–36.65; favouring non‐surgical management).

Conclusion

There was no significant difference in the general health outcome or ankle function for patients treated surgically versus non‐surgically at 12 months. Further follow‐up is needed to evaluate longer‐term ankle function.