bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate ofAchromobacter xylosoxidans
Authors: Fleurbaaij Frank , Henneman Alex A. , Corver Jeroen , Knetsch Cornelis W. , Smits Wiep Klaas , Nauta Sjoerd T. , Giera Martin , Dragan Irina , Kumar Nitin , Lawley Trevor D. , Verhoeven Aswin , van Leeuwen Hans C. , Kuijper Ed J. , Hensbergen Paul J.
Published: September 2017

The development of antibiotic resistance during treatment is a threat to patients and their environment. Insight in the mechanisms of resistance development is important for appropriate therapy and infection control. Here, we describe how through the application of mass spectrometry-based proteomics, a novel beta-lactamase Axc was identified as an indicator of acquired carbapenem resistance in a clinical isolate ofAchromobacter xylosoxidans.

Comparative proteomic analysis of consecutively collected susceptible and a resistant isolates from the same patient revealed that high Axc protein levels were only observed in the resistant isolate. Heterologous expression of Axc inEscherichia colisignificantly increased the resistance towards carbapenems. Importantly, direct Axc mediated hydrolysis of imipenem was demonstrated using pH shift assays and1H-NMR, confirming Axc as a legitimate carbapenemase. Whole genome sequencing revealed that the susceptible and resistant isolates were remarkably similar.

Together these findings provide a molecular context for the fast development of meropenem resistance inA. xylosoxidansduring treatment and demonstrate the use of mass spectrometric techniques in identifying novel resistance determinants.
Cyclin A2 localises in the cytoplasm at the S/G2 transition to activate PLK1
Authors: Cascales Helena Silva , Burdova Kamila , Middleton Anna , Kuzin Vladislav , Müllers Erik , Stoy Henriette , Baranello Laura , Macurek Libor , Lindqvist Arne
Published: September 2017

Cyclin A2 is a key regulator of the cell cycle, implicated both in DNA replication and mitotic entry. Cyclin A2 participates in feedback loops that activate mitotic kinases in G2-phase, but why active Cyclin A2-CDK2 during S phase does not trigger mitotic kinase activation remains unclear. Here we describe a change in localisation of Cyclin A2 from being only nuclear to both nuclear and cytoplasmic at the S/G2 border. We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1. Expression of predominately cytoplasmic Cyclin A2 or phospho-mimicking PLK1 T210D can partially rescue a G2 arrest caused by Cyclin A2 depletion. Cytoplasmic presence of Cyclin A2 is restricted by p21, in particular after DNA damage. Cyclin A2 chromatin association during DNA replication and additional mechanisms contribute to Cyclin A2 localisation change in G2 phase. We find no evidence that such mechanisms involve G2 feedback loops and suggest that cytoplasmic appearance of Cyclin A2 at the S/G2 transition functions as a trigger for mitotic kinase activation.

Synopsis

Main mitotic kinases as PLK1 are activated at the S/G2 transition. A change in Cyclin A2 localisation at the S/G2 transition enables activation of PLK1.

Main points

-Cyclin A2 appears in the cytoplasm at the S/G2 transition

-Association with replicating chromatin and p21 restricts Cyclin A2 to the nucleus

-DNA damage ensures nuclear Cyclin A2 through p21

-Cytoplasmic Cyclin A2 initiates PLK1 activation

Graphical abstract
Genetic Identification of Novel Separase regulators inCaenorhabditis elegans
Authors: Melesse Michael , Sloan Dillon E. , Benthal Joseph T. , Caylor Quincey , Gosine Krishen , Bai Xiaofei , Bembenek Joshua N.
Published: September 2017

Separase is a highly conserved protease required for chromosome segregation. Although observations that separase also regulates membrane trafficking events have been made, it is still not clear how separase achieves this function. Here we present an extensive ENU mutagenesis suppressor screen aimed at identifying suppressors ofsep-1(e2406), a temperature sensitive maternal effect embryonic lethal separase mutant. We screened nearly a million haploid genomes, and isolated sixty-eight suppressed lines. We identified fourteen independent intragenicsep-1(e2406)suppressed lines. These intragenic alleles map to seven SEP-1 residues within the N-terminus, compensating for the original mutation within the poorly conserved N-terminal domain. Interestingly, 47 of the suppressed lines have novel mutations throughout the entire coding region of thepph-5phosphatase, indicating that this is an important regulator of separase. We also found that a mutation near the MEEVD motif of HSP-90, which binds and activates PPH-5, also rescuessep-1(e2406)mutants. Finally, we identified six potentially novel suppressor lines that fall into five complementation groups. These new alleles provide the opportunity to more exhaustively investigate the regulation and function of separase.
Nano-scale size holes in ER sheets provide an alternative to tubules for highly-curved membranes
Authors: Schroeder Lena K. , Barentine Andrew E. S. , Schweighofer Sarah , Baddeley David , Bewersdorf Joerg , Bahmanyar Shirin
Published: September 2017

The endoplasmic reticulum (ER) is composed of interconnected membrane sheets and tubules. Super-resolution microscopy recently revealed densely packed, rapidly moving ER tubules, highlighting the importance of revisiting classical views of ER structure with high spatial resolution in living cells. Using live-cell Stimulated Emission Depletion (STED) microscopy, we show highly dynamic, subdiffraction-sized holes in ER sheets. Holes coexist with uniform sheet regions and are distinct from tubular ER structures. The curvature-stabilizing reticulon protein Rtn4 localizes to these holes and the ER luminal tether Climp63 controls their diameter and mobility. Analytical modeling demonstrates that holes in ER sheets can serve as reservoirs for curvature-stabilizing proteins to support ER tubule extension and retraction, thus providing an explanation for how the ER locally alters its morphology on fast time-scales.

One Sentence Summary

Dynamic nano-scale sized holes are prominent features of ER sheets that serve as reservoirs for curvature-stabilizing proteins to support ER tubule extension and retraction.
PyFolding: An open-source software package for graphing, simulation and analysis of the biophysical properties of proteins
Authors: Lowe Alan R. , Perez-Riba Albert , Itzhaki Laura S. , Main Ewan R.G.
Published: September 2017

Abstract]

For many years, curve fitting software has been heavily utilized to fit simple models to various types of biophysical data. Although such software packages are easy to use for simple functions, they are often expensive and present substantial impediments to applying more complex models or for the analysis of large datasets. One field that is relient on such data analysis is the thermodynamics and kinetics of protein folding. Over the past decade, increasingly sophisticated analytical models have been generated, but without simple tools to enable routine analysis. Consequently, users have needed to generate their own tools or otherwise find willing collaborators. Here we presentPyFolding, a free, open source, and extensible Python framework for graphing, analysis and simulation of the biophysical properties of proteins. To demonstrate the utility ofPyFolding, we have used it to analyze and model experimental protein folding and thermodynamic data. Examples include: (i) multi-phase kinetic folding fitted to linked equations, (ii) global fitting of multiple datasets and (iii) analysis of repeat protein thermodynamics with Ising model variants. Moreover, we demonstrate howPyfoldingis easily extensible to novel functionality beyond applications in protein folding via the addition of new models. Example scripts to perform these and other operations are supplied with the software, and we encourage users to contribute notebooks and models to create a community resource. Finally, we show thatPyFoldingcan be used in conjunction with Jupyter notebooks as an easy way to share methods and analysis for publication and amongst research teams.
Targeting histone deacetylase activity to arrest cell growth and promote neural differentiation in Ewing sarcoma
Authors: Souza Bárbara Kunzler , Costa Lopez Patrícia Luciana da , Menegotto Pâmela Rossi , Vieira Igor Araujo , Kersting Nathalia , Abujamra Ana Lúcia , Brunetto André T. , Brunetto Algemir L. , Gregianin Lauro , de Farias Caroline Brunetto , Thiele Carol J. , Roesler Rafael
Published: September 2017

There is an urgent need for advances in the treatment of Ewing sarcoma (EWS), an aggressive childhood tumor with possible neuroectodermal origin. Inhibition of histone deacetylases (HDAC) can revert aberrant epigenetic states and reduce growth in different experimental cancer types. Here, we investigated whether the potent HDAC inhibitor, sodium butyrate (NaB) has the ability to reprogram EWS cells towards a more differentiated state and affect their growth and survival. Exposure of two EWS cell lines to NaB resulted in rapid and potent inhibition of HDAC activity (1 h, IC501.5 mM) and a significant arrest of cell cycle progression (72 h, IC500.68-0.76 mM), marked by G0/G1 accumulation. Delayed cell proliferation and reduced colony formation ability were observed in EWS cells after long-term culture. NaB-induced effects included suppression of cell proliferation accompanied by reduced transcriptional expression of theEWS-FLI1fusion oncogene, decreased expression of key survival and pluripotency-associated genes, and re-expression of the differentiation neuronal marker ²III-tubulin. Finally, NaB reduced c-MYC levels and impaired survival in putative EWS cancer stem cells. Our findings support the use of HDAC inhibition as a strategy to impair cell growth and survival and to reprogram EWS tumors towards differentiation. These results are consistent with our previous studies indicating that HDis can inhibit the growth and modulate differentiation of cells from other types of childhood pediatric tumors possibly originating from neural stem cells.
A simplified electronic circuit for combined single-cell stimulation and recording using loose cell-attached electrodes
Authors: Strowbridge Ben W. , Todd Pressler R.
Published: September 2017

While tight-seal patch clamp recordings have found wide use in neuroscience and in other fields, the requirement to replace the glass pipette after every attempted recording represents an impediment to high throughput studies such as searching for monosynaptically connected pairs of neurons. Loose cell-attached recording was introduced in 2000 to circumvent this problem since it enabled combined recording and stimulation of visually-identified neurons without necessitating a tight (gigaohm) seal. Since the stimulus voltages required to evoke action potentials through low resistance seals are beyond the capacity of most commercial amplifiers, Barbour and Isope introduced a variation of classic patch clamp amplifier circuit that is able to deliver stimulus voltages that are effective in triggering action potentials under the loose cell-attached patch clamp configuration. The present report presents the design and operation of a simpler amplifier that contains only two integrated circuits and is able to effectively stimulate and record action potentials in mitral cells in rodent olfactory bulb slices. The addition of an accessory analog gating circuit enables manual control of the stimulus voltage with pulse timing controlled by a digital output from a computer. This system may be useful in studies that require surveying many potential pairs of neurons for synaptic connections and for sampling and manipulating single-cell activity in in vivo electrophysiology experiments.
Single-molecule diffusometry reveals the nucleotide-dependent oligomerization pathways ofNicotiana tabacumRubisco activase
Authors: Wang Quan , Serban Andrew J. , Wachter Rebekka M. , Moerner W.E.
Published: September 2017

Oligomerization plays an important role in the function of many proteins, but a quantitative picture of the oligomer distribution has been difficult to obtain using existing techniques. Here we describe a method that combines sub-stoichiometric labeling and recently-developed single-molecule diffusometry to measure the size distribution of oligomers under equilibrium conditions in solution, one molecule at a time. We use this technique to characterize the oligomerization behavior ofNicotiana tabacum(Nt) rubisco activase (Nt-Rca), a chaperone-like, AAA-plus ATPase essential in regulating carbon fixation during photosynthesis. We directly observed monomers, dimers and a tetramer/hexamer mixture, and extracted their fractional abundance as a function of protein concentration. We show that the oligomerization pathway of Nt-Rca is nucleotide dependent: ATPγS binding strongly promotes tetramer/hexamer formation from dimers and results in a preferred tetramer/hexamer population for concentrations in the 1-10μM range. Furthermore, we directly observed dynamic assembly and disassembly processes of single complexes in real time, and from there estimated the rate of subunit exchange to be ~0.1s-1with ATPγS. On the other hand, ADP binding destabilizes Rca complexes by enhancing the rate of subunit exchange by >2 fold. These observations provide a quantitative starting point to elucidate the structure-function relations of Nt-Rca complexes. We envision the method to fill a critical gap in defining and quantifying protein assembly pathways in the small-oligomer regime.
Human mobility in the context of climate change and disasters: a South American approach
Authors: Yamamoto Lilian , Serraglio Diogo Andreola , Cavedon-Capdeville Fernanda de Salles
Published: September 2017

Purpose

This paper aims to assess to what extent South American countries have integrated recommendations of the international agenda to address human mobility in the context of disasters and climate change in their national laws and policies.

Design/methodology/approach

This research sought to find the level of discussions around human mobility in disaster laws, NDCs and National Adaptation Plans (NAPs) by looking for a range of search terms connected to human mobility in the context of disasters and climate change, followed by the content analysis of these terms.

Findings

Some advances with regards to human mobility are already confirmed in the domestic level of South American countries through humanitarian visas to disaster displaced persons and the inclusion of the topic in the DRR, climate change laws, NAPs and INDCs/NDCs. But they have not developed specific strategies with regards to it. Hence, their advances still require that national norms and policies are harmonized with the international guidelines. This will enable to fill the protection gap of people in context of disasters and climate change.

Originality/value

The results assess the level of harmonization above-mentioned between international instruments with national policies on human mobility in the context of disasters and climate change in South America.
Who takes responsibility for the climate refugees?
Authors: Ahmed Bayes
Published: September 2017

Purpose

“No climate change, no climate refugees”. On the basis of this theme, this paper aims to propose a method for undertaking the responsibility for climate refugees literally uprooted by liable climate polluting countries. It also considers the historical past, culture, geopolitics, imposed wars, economic oppression and fragile governance to understand the holistic scenario of vulnerability to climate change.

Design/methodology/approach

This paper is organized around three distinct aspects of dealing with extreme climatic events – vulnerability as part of making the preparedness and response process fragile (past), climate change as a hazard driver (present) and rehabilitating the climate refugees (future). Bangladesh is used as an example that represents a top victim country to climatic extreme events from many countries with similar baseline characteristics. The top 20 countries accounting for approximately 82 per cent of the total global carbon dioxide (CO2) emissions are considered for model development by analysing the parameters – per capita CO2 emissions, ecological footprint, gross national income and human development index.

Findings

Results suggest that under present circumstances, Australia and the USA each should take responsibility of 10 per cent each of the overall global share of climate refugees, followed by Canada and Saudi Arabia (9 per cent each), South Korea (7 per cent) and Russia, Germany and Japan (6 per cent each). As there is no international convention for protecting climate refugees yet, the victims either end up in detention camps or are refused shelter in safer places or countries. There is a dire need to address the climate refugee crisis as these people face greater political risks.

Originality/value

This paper provides a critical overview of accommodating the climate refugees (those who have no means for bouncing back) by the liable countries. It proposes an innovative method by considering the status of climate pollution, resource consumption, economy and human development rankings to address the problem by bringing humanitarian justice to the ultimate climate refugees.
Biomarker of burden: Feather corticosterone reflects energetic expenditure and allostatic overload in captive waterfowl
Authors: Johns David W. , Marchant Tracy A. , Fairhurst Graham D. , Speakman John R. , Clark Robert G.
Published: September 2017

Allostatic load describes the interplay between energetic demand and availability and is highly context dependent, varying between seasons and life‐history stages. When energy demands exceed physiological set points modulated by glucocorticoid hormones, individuals may experience allostatic overload and transition between stages in sub‐optimal physiological states.

Corticosterone, the major glucocorticoid hormone regulating energy expenditure in birds, is incorporated into growing feathers (CORTf), and it has been suggested that CORTfreflects long‐term records of allostatic load during feather growth. However, relationships between allostatic load and CORTfhave not been adequately evaluated. If such relationships exist, the use of CORTfto investigate cross‐seasonal effects could provide novel insights into impacts of past allostatic load and/or overload events.

We tested whether experimental increases in daily workload during two adjacent life‐history stages would be reflected in CORTflevels, and examined if CORTflevels reflected either current energetic demand or allostatic load prior to feather growth.

Daily workloads in female mallardAnas platyrhynchosducklings were increased over a 6‐week period using physical obstacles and/or carrying back‐mounted weights. We measured daily energy expenditure, growth, body mass, and CORTfin growing ducklings. Then, we induced feather moult and reapplied combinations of workload treatments for an additional 6 weeks to investigate whether effects of past energetic demands would be detected in future CORTflevels.

Ducklings confronted with higher workloads during development had reduced body mass, growth rates and consequently higher daily energy expenditure and CORTfvalues compared to controls. When ducklings were fully developed, CORTfpatterns in birds re‐exposed to workload treatments reflected only current, rather than past, energetic demands. However, under allostatic overload conditions, past levels of CORTfwere positively associated with CORTfin the subsequent moult.

Our study confirms the previously untested assumption that CORTfreflects energetic demand during the period of feather growth in a precocial bird. We show that allostatic overload conditions early in life, which temporarily suppress growth, can be detected using CORTf, an event potentially missed in studies which rely solely on measures of body condition alone.

We suggest that CORTfcan provide a valuable biomarker of allostatic load and overload conditions during the period of feather growth, but highlight how context should be considered for studies using CORTfto investigate influences of carryover effects. Our study contributes to building a physiological foundation to inform interpretations of ecological patterns using CORTf.

Aplain language summaryis available for this article.
Mammalian herbivores affect leafhoppers associated with specific plant functional types at different timescales
Authors: Vandegehuchte Martijn L. , Trivellone Valeria , Schütz Martin , Firn Jennifer , de Schaetzen Frederic , Risch Anita C.
Published: September 2017

Theory predicts that mammalian herbivores affect the quantity and quality of plants on which they preferentially feed in the short term. In the longer term, they can promote either preferred or less preferred plants, depending on whether preferred plants are adapted or sensitive to grazing. Less clear are the short‐ and long‐term responses of herbivorous insects to mammalian herbivory, and how these responses depend on the specific plants or plant functional types on which the insects feed.

We progressively excluded large, medium and small mammals for five growing seasons in two subalpine vegetation types with long‐term differences in mammalian grazing intensity. Short‐grass vegetation has a history of intensive grazing, while tall‐grass vegetation has been grazed less intensively. We tested whether mammals altered the abundance and body size of leafhoppers specialized on specific plant functional types (grasses, sedges, forbs, or legumes/forbs), distinguishing between short‐term (exclosures) and long‐term (vegetation types) differences in mammalian grazing pressure. Furthermore, we assessed whether leafhoppers’ responses were explained by changes in biomass or quality of the plant functional types on which they feed.

In the short term, mammal exclosures increased the abundance of grass‐ and forb‐feeding leafhoppers via increases in the biomass of grasses and forbs, regardless of vegetation type. Both grasses and forbs are preferred food plants of mammals. In the long term, the biomass of sedges, which are less preferred by mammals, increased in the less intensively grazed tall‐grass vegetation. This resulted in a higher abundance of sedge‐feeding leafhoppers. The small size of these sedge feeders lowered the average leafhopper body size in the tall‐grass vegetation. Plant nutritional quality did not explain any effects of exclusions or vegetation types.

Our results demonstrate that both short‐ and long‐term effects of mammalian herbivores on the biomass of specific plant functional types caused concurrent changes in the abundance of specialized herbivorous insects, which scaled up to community‐wide shifts in insect body size, a key life‐history trait. A plant‐functional‐type approach can thus help to predict how overabundance or extinction of mammalian herbivores impacts on other components of the food web at various timescales.

A plain language summary is available for this article.
Thermoregulatory windows in Darwin's finches
Authors: Tattersall Glenn J. , Chaves Jaime A. , Danner Raymond M.
Published: September 2017

Darwin's finches have been the focus of intense study demonstrating how climatic fluctuations coupled with resource competition drive the evolution of a variety of bill sizes and shapes. The bill, as other peripheral surfaces, also plays an important role in thermoregulation in numerous bird species. The avian bill is vascularized, while limbs have specialized vasculature that facilitate heat loss or heat conservation (i.e. they are thermoregulatory windows).

The Galápagos Islands, home to Darwin's finches, have a hot and relatively dry climate for approximately half of the year, during which thermoregulatory windows (i.e. surfaces) could be important for thermoregulation and the linked challenge of water balance.

We hypothesized that Darwin's finch bills have evolved in part for their role in thermoregulation, possibly co‐opted, following adaptation for other functions, such as foraging. We predicted that bills of Darwin's finches are effective thermoregulatory windows, and that species differences in bill morphology, along with physiology and behaviour, lead to differences in thermoregulatory function.

To test these hypotheses, we conducted a field study to assess heat exchange and microclimate use in three ground finch species and sympatric cactus finch (Geospiza spp.). We collected thermal images of free‐living birds during a hot and dry season and recorded microclimate data for each observation. We used individual thermographic data to model the contribution of bills, legs and bodies to overall heat balance and compared surface temperatures to those from dead birds to test physiological control of heat loss from these surfaces. We derived and compared species‐specific threshold environmental temperatures, which are indicative of a species’ thermally neutral temperature.

In all species, the bill surface was an effective heat dissipater during naturally occurring warm temperatures. As expected, we found that finches controlled surface temperatures through physiology and that young birds had higher surface temperatures than adults. Larger bills contributed proportionally more to overall heat loss than smaller bills.

We demonstrate here that related, sympatric species with different bill sizes exhibit different patterns in the use of these thermoregulatory structures, supporting a role for thermoregulation in the evolution and ecology of Darwin's finch morphology.

A plain language summary is available for this article.
Insulin‐like growth factor 1 and life‐history evolution of passerine birds
Authors: Lodjak Jaanis , Mänd Raivo , Mägi Marko
Published: September 2017

Natural selection has generated a diversity of ways in which vertebrates allocate their resources between fundamental life‐history traits. The availability of possible evolutionary trajectories of these traits is limited by various genetic, physiological and phylogenetic constraints. This causes trade‐offs due to shared resource pools for, or genetic linkage of, competing traits. The majority of these trade‐offs are mediated by hormones and create the variability in phenotypes that can be observed in nature.

Insulin‐like growth factor 1 (IGF‐1) is an evolutionarily conserved peptide, which has been shown to be essential in the regulation of body size, the pattern of reproductive investment and life span across a broad taxonomic range of model species in laboratory and domesticated conditions. However, studies addressing corresponding evolutionary hypotheses on a broader scale and in free‐living vertebrates are very rare.

In this phylogenetic comparative study on free‐living passerines (Passeriformes), we explore the way in which plasma IGF‐1 levels underlie the evolution of body size and demographic fitness correlates (clutch size, egg weight, life span).

We showed firstly that IGF‐1 levels were positively associated with the body size of passerines, although smaller birds had larger IGF‐1‐mediated investment into building up their body faster. IGF‐1 levels were negatively associated with life span of passerines, and more so in birds with smaller body weight. Finally, IGF‐1 levels were negatively associated with clutch size in heavier species, and positively associated with egg weight in species with higher body weight and longer duration of parental care. The pattern was opposite in species with smaller body weight and shorter duration of parental care.

The described evolutionary framework indicates that variation in IGF‐1 levels can be regarded as an important mechanism that may underlie life‐history evolution in passerines. IGF‐1 could act as a physiological link mediating the inter‐regulatory growth–reproduction–lifespan “life‐history triangle” on the pace‐of‐life continuum. Interestingly, body weight and investment into parental care have likely imposed a constraining effect on the IGF‐1‐mediated co‐evolution of demographic fitness traits, such as life span or reproductive investment. This has limited the availability of adaptive pathways via which those traits could evolve as passerines diversified.

A plain language summary is available for this article.
The Variegated Financialization of Housing
Authors: Aalbers Manuel B.
Published: September 2017

There is a small but growing literature on the financialization of housing that demonstrates how housing is a central aspect of financialization. Despite the varied analyses of the financialization of housing and the importance of housing to financialization, the relations between housing and financialization remain under‐researched and under‐theorized. The financialization of housing is not really a specific form of financialization, transcending as it does a number of different forms of financialization. Housing systems, in particular, vary widely across the globe, which implies that housing financialization will be inherently variegated, path‐dependent and uneven. In this introduction to the symposium, I will discuss how the articles to follow contribute to the literature on the financialization of housing. Housing has entered a post‐Fordist, neoliberal and financialized regime. Increasingly, both mortgaged homeownership and subsidized rental housing are there to keep financial markets going, rather than being facilitated by those markets. There is little evidence that the global financial crisis has resulted in any de‐financialization of housing. There are common trajectories within uneven and variegated financialization, rather than radically different and completely unrelated forms of housing financialization.
Production of reduced‐fat Labneh cheese with inulin and β‐glucan fibre‐based fat replacer
Authors: Aydinol Pinar , Ozcan Tulay
Published: September 2017

The beneficial role of dietary fibre in human nutrition and effects of properties on fermented dairy products have led to a growing demand for the incorporation of novel fibre‐based fat replacers. The aim of the present work was to investigate the possibility of using inulin and oat‐based β‐glucan in Labneh cheese and to analyse the physico‐chemical, textural and sensory properties of the resulting product. The results showed that the textural and sensory properties of the cheese with addition of inulin increased at a 12% fat ratio. Overall, full‐fat and reduced‐fat Labneh cheeses were firmer and had better flavour than all the low‐fat cheeses. However, inulin and oat β‐glucan, as fermentable fibres, were also degraded as fermentable fibres to produce organic acids and had the potential for use as fat replacers in low‐fat dairy systems.
Identification of lipopeptide xantholysins from Pseudomonas sp. DJ15 and their insecticidal activity against Myzus persicae
Authors: Lim Da Jung , Yang Si Young , Noh Mi Young , Lee Chul Won , Kim Jin Cheol , Kim In Seon
Published: September 2017

Myzus persicae is an important insect pest that reduces crop production worldwide. The use of pesticides for aphid control has generated much concern related to insect resistance and undesirable environmental effects. In an effort to discover new alternatives to counter M. persicae, we found that Pseudomonas isolate DJ15 produced insecticidal metabolites. To isolate the insecticidal metabolites, a cell‐free supernatant of DJ15 was extracted and subjected to bioassay‐guided chromatography. Based on the structures elucidated in instrumental analyses, the metabolites were identified as xantholysins A and B. The metabolites showed strong insecticidal activity against M. persicae with 50% mortality at levels of 13.4 and 24.6 μg/mL for xantholysins A and B, respectively. This is the first study to identify xantholysins as insecticidal metabolites against M. persicae.
Evaluation of periostin and factors associated with new bone formation in ankylosing spondylitis: Periostin may be associated with the Wnt pathway
Authors: Solmaz Dilek , Uslu Sadettin , Kozacı Didem , Karaca Neslihan , Bulbul Hale , Tarhan Emine Figen , Ozmen Mustafa , Can Gercek , Akar Servet
Published: September 2017

Objective

Periostin has been shown to be involved in bone anabolism through the regulation of Wnt‐β‐catenin signaling. It may be one of the pathogenic mechanisms in syndesmophyte formation in ankylosing spondylitis (AS). The aim of this study was to evaluate serum periostin levels in patients with AS and to assess relationships among biomarkers of bone formation and periostin in disease outcomes, particularly radiographic changes.

Methods

Ninety‐seven consecutive AS patients (78% male) and 48 healthy controls (75% male) were included in the study. Serum periostin, dickkopf‐1 (DKK‐1), sclerostin and vascular endothelial growth factor (VEGF) levels were measured using commercially available enzyme‐linked immunosorbent assay kits. Disease‐related characteristics of patients were assessed using Ankylosing spondylitis disease activity score – C‐reactive protein (ASDAS‐CRP), Bath AS Disease Activity Index, Bath AS Functional Index and Bath AS metrology index. Radiographs were scored using the modified New York criteria and modified Stokes AS spinal score (mSASSS).

Results

Compared with control subjects, patients with AS had significantly lower serum levels of periostin (P < 0.001) and sclerostin (P < 0.001), but higher serum levels of VEGF (P < 0.001) and high‐sensitivity CRP (P < 0.001). Serum periostin (P = 0.005) and sclerostin levels (P = 0.016) were significantly lower in patients with very high disease activity according to ASDAS‐CRP. Current age (P = 0.009), age at symptom onset (P = 0.021) and hip joint involvement (P = 0.012) were independently associated with the development of syndesmophyte, in contrast to biomarkers of bone metabolism that we evaluated.

Conclusion

Our results suggest that periostin is down‐regulated in AS patients with highly active disease and may contribute to disease pathogenesis through an interaction with Wnt signaling.
Increased thalamic resting‐state connectivity as a core driver of LSD‐induced hallucinations
Authors: Müller F. , Lenz C. , Dolder P. , Lang U. , Schmidt A. , Liechti M. , Borgwardt S.
Published: September 2017

Objective

It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system.

Method

100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI‐to‐ROI and ROI‐to‐voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects.

Results

LSD caused significant alterations in all dimensions of the 5D‐ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD‐induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects.

Conclusion

Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5‐HT2A‐receptor in altered states of consciousness.
Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta‐analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate
Authors: Palpacuer Clément , Duprez Renan , Huneau Alexandre , Locher Clara , Boussageon Rémy , Laviolle Bruno , Naudet Florian
Published: September 2017

Background and Aims

Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication.

Design

Systematic review with direct and network meta‐analysis of double‐blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non‐abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data.

Setting

Thirty‐two RCTs.

Participants

A total of 6036 patients.

Measurements

The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes.

Findings

No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = −0.19, 95% confidence interval (CI) = −0.29, –0.10; I2 = 0%], baclofen (SMD = −1.00, 95% CI = −1.80, −0.19; one study) and topiramate (SMD = −0.77, 95% CI = −1.12, –0.42; I2 = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor.

Conclusions

There is currently no high‐grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes.
Fracture resistance of simulated immature teeth after internal bleaching procedures
Authors: Uzunoglu Emel , Eymirli Ayhan , Uyanik Mehmet Özgür , Nagas Emre , Çehreli Zafer Cavit
Published: September 2017

The aim of this study was to evaluate the fracture resistance of simulated immature teeth after internal bleaching. The teeth were assigned as follows (n = 12/group); Group‐1: The pulp chamber was filled with ProRootMTA and bleached intracoronally with sodium perborate mixed with 37% carbamide peroxide gel; Group‐2: The pulp chamber was filled with ProRootMTA without bleaching; Group‐3: The pulp chamber was filled with Biodentine and bleached intracoronally as Group‐1; Group‐4: The pulp chamber was filled with Biodentine without bleaching; and Group‐5: Teeth received no intervention (control). The specimens were loaded vertically until root fracture occurred. The data were analysed with Kruskal–Wallis and Dunn tests. There was no significant difference between the fracture resistances of the experimental groups (P > 0.05). However, all experimental groups had significantly lower fracture resistance than the control group (P < 0.05). Neither the tested calcium silicate cements nor the bleaching procedures had a significant impact on fracture resistance values.
Skull of the grey heron (Ardea cinerea): Detailed investigation of the orbital region
Authors: Bavdek S. V. , Golob Z. , Janžekovič F. , Rutland C. S. , Kubale V.
Published: September 2017

The skull of the grey heron (Ardea cinerea) was examined with an emphasis on describing the orbital region. In the young (circa sixteen to seventeen days old) heron, the frontal bone (os frontale) and nasal bone (os nasale) comprised separate paired bones, connected by sutures (sutura interfrontalis, sutura internasalis and sutura frontonasalis plana). In adult animals, the relationship between these bones was different: the left and right frontal bone and the left and right nasal bone had grown together, and the frontal bone and nasal bone had fused into a common frontonasal bone (os frontonasale). In the ectethmoid bone (os ectethmoidale), the main components comprised of the orbital and antorbital part of the ectethmoid plate (lamina ectethmoidalis orbitalis et antorbitalis), the lateral process (processus lateralis ectethmoidalis) and the tubercle (tuberculum ectethmoidalis); the left and right ectethmoid plates were fused together to form the ectethmoid sinus (sinus ectethmoidalis) between them. In the young heron, the anatomical and functional link between the frontal and lacrimal bones did not exist yet, nor did the osseous frame of the ectethmoid‐lacrimal complex. Further research into the young heron skulls is needed. This article provides novel insights into the grey heron's orbital region.
Evaluation of Combined Extracorporeal Life Support and Continuous Renal Replacement Therapy on Hemodynamic Performance and Gaseous Microemboli Handling Ability in a Simulated Neonatal ECLS System
Authors: Shank Kaitlyn R. , Profeta Elizabeth , Wang Shigang , O'Connor Christian , Kunselman Allen R. , Woitas Karl , Myers John L. , Ündar Akif
Published: September 2017

The objective of this study was to evaluate the hemodynamic performance and gaseous microemboli (GME) handling ability of a simulated neonatal extracorporeal life support (ECLS) circuit with an in‐line continuous renal replacement therapy (CRRT) device. The circuit consisted of a Maquet RotaFlow centrifugal pump or HL20 roller pump, Quadrox‐iD Pediatric diffusion membrane oxygenator, 8‐Fr arterial cannula, 10‐Fr venous cannula, and Better‐Bladder (BB) with “Y” connector. A second Quadrox‐I Adult oxygenator was added postarterial cannula for GME experiments. The circuit and pseudo‐patient were primed with lactated Ringer's solution and packed human red blood cells (hematocrit 40%). All hemodynamic trials were conducted at ECLS flow rates ranging from 200 to 600 mL/min and CRRT flow rate of 75 mL/min at 36°C. Real‐time pressure and flow data were recorded with a data acquisition system and GME were detected and characterized using the Emboli Detection and Classification Quantifier System. CRRT was added at distinct locations such that blood entered CRRT between the pump and oxygenator (A), recirculated through the pump (B), or bypassed the pump (C). With the centrifugal pump, all CRRT positions had similar flow rates, mean arterial pressure (MAP), and total hemodynamic energy (THE) loss. With the roller pump, C demonstrated increased flow rates (293.2–686.4 mL/min) and increased MAP (59.4–75.5 mm Hg) (P < 0.01); B had decreased flow rates (129.7–529.7 mL/min), and MAP (34.2–45.0 mm Hg) (P < 0.01); A maintained the same when compared to without CRRT. At 600 mL/min C lost more THE (81.4%) (P < 0.01) with a larger pressure drop across the oxygenator (95.6 mm Hg) (P < 0.01) than without CRRT (78.3%; 49.1 mm Hg) (P < 0.01). C also demonstrated a poorer GME handling ability using the roller pump, with 87.1% volume and 17.8% count reduction across the circuit, compared to A and B with 99.9% volume and 65.8–72.3% count reduction. These findings suggest that, in contrast to A and B, adding CRRT at position C is unsafe and not advised for clinical use.
Respiratory morbidity was an important consequence of prematurity in the first two years after discharge in three cohorts from 1996 to 2009
Authors: Mulder Estelle E. M. , Rijken Monique , de Smet Lotte , Pauws Steffen , Lopriore Enrico , te Pas Arjan B.
Published: September 2017

Aim

This study aimed to evaluate the respiratory morbidity of preterm infants in the first two years after discharge in three cohorts from 1996 to 2009.

Methods

We included infants with a gestational age from 25 + 0 to 29 + 6 weeks, who were born in 1996–1997, 2003–2004 and 2008–2009 at the Leiden University Medical Center in the Netherlands. The following parameters were recorded: bronchopulmonary dysplasia (BPD), defined as oxygen demand or positive pressure at 36 weeks, mortality, duration of supplemental oxygen, discharge with supplemental oxygen and a nasogastric feeding tube, rehospitalisation and the use of inhaled medication.

Results

In line with our protocols, 106, 120 and 156 infants were analysed in the three study periods and 29%, 22% and 18% were diagnosed with BPD. Respiratory morbidity did not change over time in infants with and without BPD, except for an increase in rehospitalisation for respiratory issues in infants with BPD. This decreased in infants without BPD. Respiratory morbidity occurred more frequently in infants with BPD than without BPD, but this was not statistically significant.

Conclusion

This study showed that when cohorts of preterm infants were compared over time, respiratory morbidity in the first two years of life remained an important consequence after discharge.
Treatment of refractory ascites with an automated low‐flow ascites pump in patients with cirrhosis
Authors: Stirnimann G. , Berg T. , Spahr L. , Zeuzem S. , McPherson S. , Lammert F. , Storni F. , Banz V. , Babatz J. , Vargas V. , Geier A. , Stallmach A. , Engelmann C. , Trepte C. , Capel J. , De Gottardi A.
Published: September 2017

Background

Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low‐flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.

Aim

To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS.

Methods

Fifty‐six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded.

Results

At the time of this analysis, 3 patients completed the 24‐month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty‐three pump‐related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow‐up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month.

Conclusions

The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions.

https://clinicaltrials.gov/ct2/show/NCT01532427