bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylglyoxal is associated with changes in kidney function among individuals with screen‐detected Type 2 diabetes mellitus
Authors: Jensen T. M. , Vistisen D. , Fleming T. , Nawroth P. P. , Rossing P. , Jørgensen M. E. , Lauritzen T. , Sandbæk A. , Witte D. R.
Published: August 2016

Aims

The glycolysis‐derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6‐year follow‐up in 1481 people with screen‐detected Type 2 diabetes, as part of the Danish arm of the ADDITION‐Europe trial (ADDITION‐DK).

Methods

Biobank serum samples collected at ADDITION‐DK baseline (2001–2006) and follow‐up (2009–2010) were used in the current analysis of methylglyoxal. We assessed cross‐sectional baseline and longitudinal associations between methylglyoxal and urinary albumin‐to‐creatinine ratio (ACR) or estimated GFR (eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR.

Results

Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow‐up was inversely associated with change in eGFR (–1.6 ml/min/1.73 m2 per doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c, systolic blood pressure, anti‐hypertensive treatment, LDL‐cholesterol, lipid‐lowering treatment, C‐reactive protein and smoking.

Conclusions

In a population of people with screen‐detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6‐year change in methylglyoxal was inversely associated with 6‐year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy.
Gas exchange pattern in the two‐spot ladybird beetle, Adalia bipunctata, differs in dry vs. moist air
Authors: Jõgar Katrin , Kuusik Aare , Metspalu Luule , Ploomi Angela , Williams Ingrid H. , Hiiesaar Külli , Luik Anne , Sibul Ivar , Mänd Marika
Published: August 2016

Gas exchange patterns in the ladybird beetle, Adalia bipunctata (L.) (Coleoptera: Coccinellidae), were investigated using an infrared gaseous analyser (IRGA) and a coulometric O2 respirometer (manometric–volumetric system). Before testing, the beetles were kept either in dry (dehydrated) or moist (hydrated) conditions for 1 day. Their subsequent gas exchange patterns did not depend on their state of humidity but rather were controlled by the humidity of the insect chamber during gas exchange measurement. If this chamber contained dry air, the beetles exhibited CO2 release by burst, which we interpreted as cyclic gas exchange (CGE) with inter‐burst periods, but if the chamber was switched to contain moist air, then cyclic CO2 release was soon abandoned and a pattern of continuous gas exchange appeared. Measurements with the coulometric respirometer in moist air showed that continuous gas exchange was often associated with weak abdominal pulsations, which we interpreted as active ventilation. Their metabolic rate was lower during gas exchange cycles than during continuous gas exchange. We revealed that in the ladybird beetle metabolic rate increased in moist air when the gas exchange pattern transitioned from cyclic to continuous.
Antennal and behavioural responses of the spruce seed moth, Cydia strobilella, to floral volatiles of Norway spruce, Picea abies, and temporal variation in emission of active compounds
Authors: Jakobsson Johan , Svensson Glenn P. , Löfstedt Christer , Anderbrant Olle
Published: August 2016

We investigated whether spruce seed moth, Cydia strobilella L. (Lepidoptera: Tortricidae, Grapholitini), one of the most damaging seed predators on Norway spruce, Picea abies (L.) H. Karst (Pinaceae), uses olfactory cues during host search. Analyses with coupled gas chromatography and electroantennography revealed that antennae of both sexes of moths responded consistently to three compounds in the headspace from female spruce flowers, i.e., α‐pinene, β‐pinene, and myrcene, but not to limonene as has been previously reported for this species. The amounts of these active volatiles released from flowers and cones of P. abies were quantified, and their diurnal and seasonal variation was monitored. The total release of the active volatiles correlated well with the diurnal and seasonal flight activity of C. strobilella as revealed by catches of males in pheromone‐baited traps. In field trapping experiments, where baits were loaded with proportions and enantiomeric ratios of α‐pinene, β‐pinene, and myrcene matching those of the female P. abies floral headspace, substantial catches of male C. strobilella were achieved, whereas few females were captured. These surprising results suggest that male C. strobilella make use of host volatiles to aid them in their search for females.
Effect of rock fragments on soil porosity: a laboratory experiment with two physically degraded soils
Authors: Gargiulo L. , Mele G. , Terribile F.
Published: August 2016

There are still few studies on the role that rock fragments (RFs) have in the change in soil structure based on direct observation of the soil‐pore system. Physically degraded soil is of particular interest because small RFs might be considered a factor in its remediation. In our laboratory experiment we mixed five different proportions of 4–8‐mm sized RFs with a Luvisol and a Regosol that have poor ability to self‐structure and were characterized by a massive structure in the field. Nine wetting and drying cycles were applied to repacked samples (15 cm in diameter and height) of soil–RF mixtures to facilitate the formation of soil structure. Image analysis was used to quantify development of the pore system at varying RF contents. The physically degraded soils studied in this research initially showed a decrease and then an increase in porosity with increasing amounts of RFs in the soil–RF mixtures. The results indicated that the Regosol responded more than the Luvisol to RF content. Threshold values of RF content at which the mechanism of pore formation prevails over that of pore reduction depended upon the soil type and can be attributed reasonably to small differences in the coefficient of linear extensibility (COLE). We also identified a mechanism for the propagation of porosity downwards from the soil surface with increasing RF content, together with a vertical homogenization effect on porosity. Our results contribute to understanding the mechanisms by which small rock fragments embedded in physically degraded topsoil induce changes in the pore system and confirm the potential of rock fragments to protect soil structure in soil susceptible to compaction.

Highlights

Physical interaction between rock fragments and fine earth in degraded soil.

Soil porosity examined by combined experimental laboratory approach with image analysis.

Soil porosity first decreases then increases with increasing content of rock fragments.

Coexistence of two opposing mechanisms: one of porosity reduction and one of formation of new pores.
Postfeminism, Men, Masculinities and Work: A Research Agenda for Gender and Organization Studies Scholars
Authors: Rumens Nick
Published: August 2016

Mobilizing the concept of postfeminism as a sensibility, this article invites organization and gender scholars to examine how postfeminist masculinities are discursively constituted and performed by men within contemporary work contexts. Acknowledging that women are interpellated within postfeminist discourses as empowered and autonomous subjects whose lives are shaped by individual choice, this article explores the implications for men, in particular how men variously perform postfeminist masculinities and the implications for addressing gendered inequalities within the workplace. Developing a research agenda, this article outlines three research trajectories: (1) problematizing a gender binary in which women are depicted as empowered at work and men in a state of crisis; (2) interrogating signs of ‘new’ postfeminist masculinities coded as inclusive in the workplace; and (3) examining how different types of men perform postfeminist masculinities at work. This article concludes by providing examples of research questions to generate future organizational scholarship in these areas.
Becoming business critical: Knowledge for Healthcare
Authors: Lacey Bryant Sue , Stewart David , Goswami Louise , Grant Maria J.
Published: August 2016

Significant progress has been made in implementing Knowledge for Healthcare. This editorial reports the central contribution of effective partnerships and the involvement of librarians and knowledge specialists in this work. There are compelling business priorities. Key elements of work‐streams on demonstrating impact, workforce development and streamlining are indicated, along with areas of growing importance – knowledge management, embedded roles and health information for the public and patients. Knowledge, and the skills to help people to use it, are business critical.
EMPLOYMENT PROTECTION, TECHNOLOGY CHOICE, AND WORKER ALLOCATION
Authors: Bartelsman Eric J. , Gautier Pieter A. , De Wind Joris
Published: August 2016

We show empirically that high‐risk sectors, which contribute strongly to aggregate productivity growth, are relatively small and have relatively low productivity growth in countries with strict employment protection legislation (EPL). To understand these findings, we develop a two‐sector matching model where firms endogenously choose between a safe technology and a risky technology. For firms that have chosen the risky technology, EPL raises the costs of shedding workers in case they receive a low productivity draw. According to our calibrated model, high‐EPL countries benefit less from the arrival of new risky technologies than low‐EPL countries. Parameters estimated through reduced‐form regressions of employment and productivity on exit costs, riskiness, and in particular their interaction are qualitatively similar for actual cross‐country data and simulated model data. Our model is consistent with the slowdown in productivity in the European Union relative to the United States since the mid‐1990s.
Predictors of intraspecific morphological variability in a tropical hotspot: comparing the influence of random and non‐random factors
Authors: Maestri Renan , Fornel Rodrigo , Gonçalves Gislene Lopes , Geise Lena , de Freitas Thales Renato Ochotorena , Carnaval Ana Carolina
Published: August 2016

Aim

We describe patterns of skull size and shape variation in an Atlantic forest endemic rodent to test the influence of genetic structure, historical and environmental variables upon intraspecific morphological variability.

Location

South America, Brazil, Atlantic forest.

Methods

We analyse subtle differences in skull morphology of Akodon cursor through geometric morphometrics applied to 324 individuals from 12 localities distributed throughout the species range. Using cytochrome‐b gene (cyt‐b) sequences from 125 individuals (38 localities), we describe underlying patterns of genetic structure and transform them into distance measures that are included in our morphological analyses. We estimate the relative importance of genetic structure, historical variables and environmental variables on skull size and shape through mixed model selection and Akaike's information criterion.

Results

Geographical patterns in skull size are mainly explained by non‐random factors related to primary productivity and precipitation, whereas spatial shifts in shape correlate with mitochondrial divergence. Cytochrome‐b data revealed a phylogeographic break around the Jequitinhonha River, yet striking morphological shifts were observed further south. Differences in palaeostability between regions, and the configuration of rivers, appear as secondary sources of explanation for observed patterns.

Main conclusions

Multiple forces explain morphological variation within A. cursor. Teasing apart the effects of local adaptation and gene flow may be difficult, but is a key to improve our understanding of the drivers of intraspecific morphological variation. Our findings support the view that size is a more labile feature than shape, and that it may more easily break away from constraints imposed by gene flow. The combination of random and non‐random factors, together with documented breaks in the distribution of the Atlantic forest over the Late Quaternary, accounts for the majority of morphological differences observed in A. cursor.
Academic Tenure
Authors: Yoon Albert H.
Published: August 2016

In academia, a subset of faculty has tenure, which allows its beneficiaries to retain their professorships without mandatory retirement and with only limited grounds for revocation. Proponents of tenure argue it protects intellectual freedom and encourages investment in human capital. Detractors contend it discourages effort and distorts the academic labor market. This article develops a framework for examining academic tenure in the context of U.S. law schools. We construct a unique data set of tenured U.S. law professors who began their careers between 1993 through 2002, and follow their employment and scholarship for the first 10 years of their career. Across all journal publications, tenured faculty publish more frequently, are cited with roughly the same frequency, and place in comparable caliber of journal. These productivity gains, however, largely disappear when excluding solicited publications. These results suggest that legal academics continue to produce after tenure, but channel more of their efforts toward less competitive outlets.
The Holocene occurrence of Acipenser spp. in the southern North Sea: the archaeological record
Authors: Thieren E. , Ervynck A. , Brinkhuizen D. , Locker A. , Van Neer W.
Published: August 2016

Archaeological sturgeon remains from the southern North Sea basin used to be automatically attributed to Acipenser sturio, since this was the only acipenserid species believed to occur there. These species identifications, however, were in need of revision after a growing number of indications were found for the historical presence of Acipenser oxyrinchus in western Europe. In this study, morphological and genetic data on sturgeon remains from archaeological sites along the southern North Sea are revised. A large number of Dutch, Belgian, British and some French archaeological sturgeon
remains, dating from the Mesolithic up to Late Modern times, are morphologically examined and fish sizes are reconstructed. This study of >7000 acipenserid bones proves the sympatric occurrence of European sturgeon A. sturio and Atlantic sturgeon A. oxyrinchus in the southern North Sea at least since the Neolithic (fourth millennium BC onwards), with A. oxyrinchus remains always outnumbering those of A. sturio. Human influence is documented by the decrease in finds through time, but no clear evidence was found for a diachronic change in fish lengths that could possibly be related to fishing pressure.
Prion‐like propagation as a pathogenic principle in frontotemporal dementia
Authors: Hock Eva‐Maria , Polymenidou Magdalini
Published: August 2016

Frontotemporal dementia is a devastating neurodegenerative disease causing stark alterations in personality and language. Characterized by severe atrophy of the frontal and temporal brain lobes, frontotemporal dementia (FTD) shows extreme heterogeneity in clinical presentation, genetic causes, and pathological findings. Like most neurodegenerative diseases, the initial symptoms of FTD are subtle, but increase in severity over time, as the disease progresses. Clinical progression is paralleled by exacerbation of pathological findings and the involvement of broader brain regions, which currently lack mechanistic explanation. Yet, a flurry of studies indicate that protein aggregates accumulating in neurodegenerative diseases can act as propagating entities, amplifying their pathogenic conformation, in a way similar to infectious prions. In this prion‐centric view, FTD can be divided into three subtypes, TDP‐43 or FUS proteinopathy and tauopathy. Here, we review the current evidence that FTD‐linked pathology propagates in a prion‐like manner and discuss the implications of these findings for disease progression and heterogeneity.

image

Frontotemporal dementia (FTD) is a progressive neurodegenerative disease causing severe personality dysfunctions, characterized by profound heterogeneity. Accumulation of tau, TDP‐43 or FUS cytoplasmic aggregates characterize molecularly distinct and non‐overlapping FTD subtypes. Here, we discuss the current evidence suggesting that prion‐like propagation and cell‐to‐cell spread of each of these cytoplasmic aggregates may underlie disease progression and heterogeneity.

This article is part of the Frontotemporal Dementia special issue.
The etemic model of Gypsy Roma Traveller community vulnerability: is it time to rethink our understanding of vulnerability?
Authors: Heaslip Vanessa , Hean Sarah , Parker Jonathan
Published: August 2016

Aims and objectives

To present a new etemic model of vulnerability.

Background

Despite vulnerability being identified as a core consequence of health and health experiences, there has been little research exploring the meaning of vulnerability as a concept. Yet, being vulnerable is known to have dire physical/mental health consequences. It is therefore a fundamental issue for nurses to address. To date, the meaning of the term vulnerability has been influenced by the work of Spiers (Journal of Advanced Nursing, 31, 2000, 715, The Essential Concepts of Nursing: Building Blocks for Practice, 2005, Elsevier, London). Spiers identified two aspects of vulnerability: the etic (external judgment of another persons’ vulnerability) and the emic (internal lived experience of vulnerability). This approach has led to a plethora of research which has explored the etic (external judgment) of vulnerability and rendered the internal lived (or emic) experience invisible. Consequences of this, for marginalised communities such as Gypsy Roma Travellers include a lack of culturally sensitive services compounding health inequalities.

Design

Position paper.

Method

Drawing upon a qualitative phenomenological research study exploring the lived experience of vulnerability from a Gypsy Roma Travelling community (published previously), this paper presents a new model of vulnerability. This etemic model of vulnerability values both external and internal dimensions of vulnerability and argues for a fusion of these two opposing perspectives.

Conclusions

If nurses and other health‐ and social care professionals wish to develop practice that is successful in engaging with Gypsy Roma Travellers, then there is a need to both understand and respect their community. This can be achieved through an etemic approach to understanding their vulnerability achieved by eliciting lived experience alongside the appreciation of epidemiological studies.

Relevance to clinical practice

If nurses and health practitioners used this etemic approach to practice then it would enable both the development and delivery of culturally sensitive services facilitating health access to this community. Only then, will their poor health status be successfully addressed.
Do organisational constraints explain the use of restraint? A comparative ethnographic study from three nursing homes in Norway
Authors: Øye Christine , Jacobsen Frode Fadnes , Mekki Tone Elin
Published: August 2016

Aims and objectives

To investigate (1) what kind of restraint is used in three nursing homes in Norway and (2) how staff use restraint under what organisational conditions.

Background

Restraint use in residents living with dementia in nursing homes is controversial, and at odds with fundamental human rights. Restraint is a matter of hindering residents’ free movement and will by applying either interactional, physical, medical, surveillance or environmental restraint. Previous research has identified use of restraint related to individual resident characteristics such as agitation, aggressiveness and wandering.

Design

This model is embedded in an overall mixed‐method education intervention design study called Modelling and evaluating evidence‐based continuing education program in dementia care (MEDCED), applying ethnography postintervention to examine the use of restraint in 24 nursing homes in Norway.

Method

Based on restraint diversity measured in the trial, ethnographic investigation was carried out in three different nursing homes in Norway over a 10‐month period to examine restraint use in relation to organisational constraints.

Results

Several forms of restraint were observed; among them, interactional restraint was used most frequently. We identified that use of restraint relates to the characteristics of individual residents, such as agitation, aggressiveness and wandering. However, restraint use should also be explained in relation to organisational conditions such as resident mix, staff culture and available human resources.

Conclusion

A fluctuating and dynamic interplay between different individual and contextual factors determines whether restraint is used – or not in particular situations with residents living with dementia.

Relevance to clinical practice

Educational initiatives targeting staff to reduce restraint must be sensitive towards fluctuating organisational constraints.
Comparison of Clinical Results Following the Use of Drug‐Eluting Balloons for a Bare‐Metal Stent and Drug‐Eluting Stent Instent Restenosis
Authors: Lee Wei‐Chieh , Fang Yen‐Nan , Fang Chih‐Yuan , Chen Chien‐Jen , Yang Cheng‐Hsu , Yip Hon‐Kan , Hang Chi‐Ling , Wu Chiung‐Jen , Fang Hsiu‐Yu
Published: August 2016

Background

Drug‐eluting balloons (DEBs) have emerged as a potential alternative to current treatments of instent restenosis (ISR). The study aims to investigate the clinical outcomes of a DEB angioplasty to treat bare‐metal stent (BMS) ISR and drug‐eluting stent (DES) ISR at 1‐year clinical follow‐up period.

Methods

Between November 2011 and December 2014, 312 patients were diagnosed with coronary artery ISR at our hospital. A total of 426 coronary ISR lesions were treated with DEBs. The clinical outcomes, including target lesion revascularization (TLR), myocardial infarction, stroke, cardiovascular mortality, and all‐cause mortality were compared between the BMS‐ISR group and DES‐ISR group. Propensity score matched analysis was used to minimize bias.

Results

The average age of the patients was 64.99 ± 10.35 years, and 76.9% of the patients were male. After multivariate Cox regression analyses about 1‐year recurrent restenosis in DES‐ISR group, only end stage renal disease (ESRD) (P = 0.047) and previous DEB failure (P < 0.001) were identified with significant difference. After propensity score matched analysis, the bias of baseline characteristics showed no significant difference. The DES‐ISR group experienced more myocardial infarctions (2.8% vs 8.3%, P = 0.075), more TLR (8.1% vs 15.4%, P = 0.051), especially at nonostial lesion (5.7% vs 14.9%, P = 0.030) than the BMS‐ISR group. Higher incidence of major cardiac cerebral adverse events happened in the DES‐ISR group. (11.7% vs 22.1 %, P = 0.038)

Conclusion

During the 1‐year follow‐up period, DEBs angioplasty for BMS‐ISR had better clinical outcomes and less TLR than DES‐ISR. ESRD and previous DEB failure were associated to TLR in DES‐ISR group.
Factors associated with poor adherence to antiviral treatment for hepatitis B
Authors: Allard N. , Dev A. , Dwyer J. , Srivatsa G. , Thompson A. , Cowie B.
Published: August 2016

Antiviral therapy for hepatitis B is effective and reduces the risk of progression to cirrhosis and liver cancer but is often required for an indefinite duration. Treatment adherence is important to prevent the development of resistance and optimize outcomes. Pharmacy adherence measures can be used to assess treatment adherence, with the medication possession ratio being less susceptible to bias than physician‐ or self‐reported adherence. The aim of this study was to measure adherence in public hospital outpatients over a 3‐year period and to examine factors associated with nonadherence. A retrospective study of pharmacy records of patients dispensed antiviral therapy for hepatitis B from four major hospitals in Melbourne between 2010 and 2013. Hospital record numbers were linked with and de‐identified demographic information including age, sex, Indigenous status, country of birth, interpreter requirement, spoken language and postcode of residence. The medication possession ratio was the outcome measure with poor adherence defined <.90. Univariate logistic regression and multivariate logistic regression were performed to examine associations with nonadherence. Records of 1026 patients were included in the analysis. Twenty per cent of all participants met the definition of poor adherence. Significant factors affecting adherence included age <35 years (P=.002), hospital site and treatment by multiple doctors within shorter time periods. This is the largest study examining detailed factors associated with adherence to hepatitis B treatment. Understanding poor adherence in clinical settings, and the factors associated with lower adherence, is important to inform efforts towards promoting treatment adherence for hepatitis B.
Iron intakes and status of 2‐year‐old children in the Cork BASELINE Birth Cohort Study
Authors: McCarthy Elaine K , ní Chaoimh Carol , Hourihane Jonathan O'B , Kenny Louise C , Irvine Alan D , Murray Deirdre M , Kiely Mairead
Published: August 2016

Young children are at risk of iron deficiency and subsequent anaemia, resulting in long‐term consequences for cognitive, motor and behavioural development. This study aimed to describe the iron intakes, status and determinants of status in 2‐year‐old children. Data were collected prospectively in the mother–child Cork BASELINE Birth Cohort Study from 15 weeks' gestation throughout early childhood. At the 24‐month assessment, serum ferritin, haemoglobin and mean corpuscular volume were measured, and food/nutrient intake data were collected using a 2‐day weighed food diary. Iron status was assessed in 729 children (median [IQR] age: 2.1 [2.1, 2.2] years) and 468 completed a food diary. From the food diary, mean (SD) iron intakes were 6.8 (2.6) mg/day and 30% had intakes < UK Estimated Average Requirement (5.3 mg/day). Using WHO definitions, iron deficiency was observed in 4.6% (n = 31) and iron deficiency anaemia in five children (1.0%). Following an iron series workup, five more children were diagnosed with iron deficiency anaemia. Twenty‐one per cent had ferritin concentrations <15 µg/L. Inadequate iron intakes (OR [95% CI]: 1.94 [1.09, 3.48]) and unmodified cows' milk intakes ≥ 400 mL/day (1.95 [1.07, 3.56]) increased the risk of low iron status. Iron‐fortified formula consumption was associated with decreased risk (0.21 [0.11, 0.41] P < 0.05). In this, the largest study in toddlers in Europe, a lower prevalence of low iron status was observed than in previous reports. Compliance with dietary recommendations to limit cows' milk intakes in young children and consumption of iron‐fortified products appears to have contributed to improved iron status at two years.
Understanding the double burden of malnutrition in food insecure households in Brazil
Authors: Gubert Muriel Bauermann , Spaniol Ana Maria , Segall‐Corrêa Ana Maria , Pérez‐Escamilla Rafael
Published: August 2016

Household food insecurity (HFI) has been associated with both obesity among mothers and undernutrition among children. However, this association has not been well investigated in mother/child pairs living in the same household. The objective of this study was to examine the relationship of coexistence of maternal overweight and child stunting with HFI in Brazil. We conducted secondary data analyses of the 2006 Brazilian National Demographic and Health Survey. We analyzed the nutritional status of 4299 pairs of 15–49‐year‐olds mothers and their children under 5 years of age. The double burden of malnutrition (DBM) was defined as the presence of an overweight mother and a stunted child in the same household. HFI was measured with the Brazilian HFI Measurement Scale. The association between DBM and HFI was examined with hierarchical multivariable logistic regression analyses. Severe HFI was associated with DBM after adjusting for macroeconomic and household level socio‐economic and demographic variables (Adjusted OR: 2.65 – CI: 1.17–8.53). Findings suggest that policies and programmes targeting HFI are needed to prevent the coexistence of child chronic undernutrition and maternal overweight/obesity in the same household. These investments are likely to be highly cost‐effective as stunting has been identified as one of the major risk factors for poor child development and adult overweight/obesity and a strong risk factor for the development of costly chronic diseases including type 2 diabetes and cardiovascular disease.
AvaR2, a pseudo γ‐butyrolactone receptor homologue from Streptomyces avermitilis, is a pleiotropic repressor of avermectin and avenolide biosynthesis and cell growth
Authors: Zhu Jianya , Sun Di , Liu Wenshuai , Chen Zhi , Li Jilun , Wen Ying
Published: August 2016

Avermectins produced by Streptomyces avermitilis are effective anthelmintic agents. The autoregulatory signalling molecule that triggers avermectin biosynthesis is a novel butenolide‐type molecule, avenolide, rather than common γ‐butyrolactones (GBLs). We identified AvaR2, a pseudo GBL receptor homologue, as an important repressor of avermectin and avenolide biosynthesis and cell growth. AvaR2 directly repressed transcription of aveR (the ave cluster‐situated activator gene), aco (a key gene for avenolide biosynthesis), its own gene (avaR2) and two other GBL receptor homologous genes (avaR1 and avaR3) by binding to their promoter regions. The aveR promoter had the highest affinity for AvaR2. A consensus 18 bp ARE (autoregulatory element)‐like sequence was found in the AvaR2‐binding regions of these five target genes. Eleven novel AvaR2 targets were identified, including genes involved in primary metabolism, ribosomal protein synthesis, and stress responses. AvaR2 bound and responded to endogenous avenolide and exogenous antibiotics jadomycin B (JadB) and aminoglycosides to modulate its DNA‐binding activity. Our findings help to clarify the roles of pseudo GBL receptors as pleiotropic regulators and as receptors for new type autoregulator and exogenous antibiotic signal. A pseudo GBL receptor‐mediated antibiotic signalling transduction system may be a common strategy that facilitates Streptomyces interspecies communication and survival in complex environments.
Shuttling of (deoxy‐) purine nucleotides between compartments of the diatom Phaeodactylum tricornutum
Authors: Chu Lili , Gruber Ansgar , Ast Michelle , Schmitz‐Esser Stephan , Altensell Jacqueline , Neuhaus Horst Ekkehard , Kroth Peter G. , Haferkamp Ilka
Published: August 2016

Diatom plastids show several peculiarities when compared with primary plastids of higher plants or algae. They are surrounded by four membranes and depend on nucleotide uptake because, unlike in plants, nucleotide de novo synthesis exclusively occurs in the cytosol. Previous analyses suggest that two specifically adapted nucleotide transporters (NTTs) facilitate the required passage of nucleotides across the innermost plastid membrane. However, nucleotide transport across the additional plastid membranes remains to be clarified.

Phylogenetic studies, transport assays with the recombinant protein as well as GFP‐based targeting analyses allowed detailed characterization of a novel isoform (PtNTT5) of the six NTTs of Phaeodactylum tricornutum.

PtNTT5 exhibits low amino acid similarities and is only distantly related to all previously characterized NTTs. However, in a heterologous expression system, it acts as a nucleotide antiporter and prefers various (deoxy‐) purine nucleotides as substrates. Interestingly, PtNTT5 is probably located in the endoplasmic reticulum, which in diatoms also represents the outermost plastid membrane.

PtNTT5, with its unusual transport properties, phylogeny and localization, can be taken as further evidence for the establishment of a sophisticated and specifically adapted nucleotide transport system in diatom plastids.
Encounters with an unearthly mudstone: Understanding the first mudstone found on Mars
Authors: Schieber Juergen , Bish David , Coleman Max , Reed Mark , Hausrath Elisabeth M. , Cosgrove John , Gupta Sanjeev , Minitti Michelle E. , Edgett Kenneth S. , Malin Mike
Published: August 2016

The Sheepbed mudstone forms the base of the strata examined by the Curiosity rover in Gale Crater on Mars, and is the first bona fide mudstone known on another planet. From images and associated data, this contribution proposes a holistic interpretation of depositional regime, diagenesis and burial history. A lake basin probably received sediment pulses from alluvial fans. Bed cross‐sections show millimetre to centimetre‐scale layering due to distal pulses of fluvial sediment injections (fine‐grained hyperpycnites), fall‐out from river plumes, and some aeolian supply. Diagenetic features include mineralized synaeresis cracks and millimetre‐scale nodules, as well as stratiform cementation. Clay minerals were initially considered due to in situ alteration, but bulk rock chemistry and mineralogy suggests that sediments were derived from variably weathered source rocks that probably contained pre‐existing clay minerals. X‐ray diffraction analyses show contrasting clay mineralogy in closely spaced samples, consistent with at least partial detrital supply of clay minerals. A significant (ca 30 wt%) amorphous component is consistent with little post‐depositional alteration. Theoretical modelling of diagenetic reactions, as well as kinetic considerations, suggest that the bulk of diagenetic clay mineral formation occurred comparatively late in diagenesis. Diagenetic features (synaeresis cracks and nodules) were previously thought to reflect early diagenetic gas formation, but an alternative scenario of synaeresis crack formation via fabric collapse of flocculated clays appears more likely. The observed diagenetic features, such as solid nodules, hollow nodules, matrix cement and ‘raised ridges’ (synaeresis cracks) can be explained with progressive alteration of olivine/glass in conjunction with centrifugal and counter diffusion of reactive species. Anhydrite‐filled fractures in the Sheepbed mudstone occurred late in diagenesis when fluid pressures built up to exceed lithostatic pressure. Generating fluid overpressure by burial to facilitate hydraulic fracturing suggests a burial depth of at least 1000 m for the underlying strata that supplied these fluids.
Evaluation of a deformable registration algorithm for subsequent lung computed tomography imaging during radiochemotherapy
Authors: Stützer Kristin , Haase Robert , Lohaus Fabian , Barczyk Steffen , Exner Florian , Löck Steffen , Rühaak Jan , Lassen‐Schmidt Bianca , Corr Dörte , Richter Christian
Published: August 2016

Purpose:

Rating both a lung segmentation algorithm and a deformable image registration (DIR) algorithm for subsequent lung computed tomography (CT) images by different evaluation techniques. Furthermore, investigating the relative performance and the correlation of the different evaluation techniques to address their potential value in a clinical setting.

Methods:

Two to seven subsequent CT images (69 in total) of 15 lung cancer patients were acquired prior, during, and after radiochemotherapy. Automated lung segmentations were compared to manually adapted contours. DIR between the first and all following CT images was performed with a fast algorithm specialized for lung tissue registration, requiring the lung segmentation as input. DIR results were evaluated based on landmark distances, lung contour metrics, and vector field inconsistencies in different subvolumes defined by eroding the lung contour. Correlations between the results from the three methods were evaluated.

Results:

Automated lung contour segmentation was satisfactory in 18 cases (26%), failed in 6 cases (9%), and required manual correction in 45 cases (66%). Initial and corrected contours had large overlap but showed strong local deviations. Landmark‐based DIR evaluation revealed high accuracy compared to CT resolution with an average error of 2.9 mm. Contour metrics of deformed contours were largely satisfactory. The median vector length of inconsistency vector fields was 0.9 mm in the lung volume and slightly smaller for the eroded volumes. There was no clear correlation between the three evaluation approaches.

Conclusions:

Automatic lung segmentation remains challenging but can assist the manual delineation process. Proven by three techniques, the inspected DIR algorithm delivers reliable results for the lung CT data sets acquired at different time points. Clinical application of DIR demands a fast DIR evaluation to identify unacceptable results, for instance, by combining different automated DIR evaluation methods.
Response to Comment on “SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML”
Authors: Fasci Domenico , Anania Veronica , Lill Jennie , Salvesen Guy
Published: August 2016

SUMO switching on an oncoprotein triggers its ubiquitylation, but not necessarily its degradation, in cells exposed to arsenic.
A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both
In Vitro
and
In Vivo
by Targeting Type IB Topoisomerase
Authors: Saha Sourav , Acharya Chiranjit , Pal Uttam , Chowdhury Somenath Roy , Sarkar Kahini , Maiti Nakul C. , Jaisankar Parasuraman , Majumder Hemanta K.
Published: August 2016

Visceral leishmaniasis is a fatal parasitic disease, and there is an emergent need for development of effective drugs against this neglected tropical disease. We report here the development of a novel spirooxindole derivative,
N
-benzyl-2,2′α-3,3′,5′,6′,7′,7α,α′-octahydro-2methoxycarbonyl-spiro[indole-3,3′-pyrrolizidine]-2-one (compound 4c), which inhibits
Leishmania donovani
topoisomerase IB (LdTopIB) and kills the wild type as well as drug-resistant parasite strains. This compound inhibits catalytic activity of LdTopIB in a competitive manner. Unlike camptothecin (CPT), the compound does not stabilize the DNA-topoisomerase IB cleavage complex; rather, it hinders drug-DNA-enzyme covalent complex formation. Fluorescence studies show that the stoichiometry of this compound binding to LdTopIB is 2:1 (mole/mole), with a dissociation constant of 6.65 μM. Molecular docking with LdTopIB using the stereoisomers of compound 4c produced two probable hits for the binding site, one in the small subunit and the other in the hinge region of the large subunit of LdTopIB. This spirooxindole is highly cytotoxic to promastigotes of
L. donovani
and also induces apoptosis-like cell death in the parasite. Treatment with compound 4c causes depolarization of mitochondrial membrane potential, formation of reactive oxygen species inside parasites, and ultimately fragmentation of nuclear DNA. Compound 4c also effectively clears amastigote forms of wild-type and drug-resistant parasites from infected mouse peritoneal macrophages but has less of an effect on host macrophages. Moreover, compound 4c showed strong antileishmanial efficacies in the BALB/c mouse model of leishmaniasis. This compound potentially can be used as a lead for developing excellent antileishmanial agents against emerging drug-resistant strains of the parasite.
Determining the Optimal Carbapenem MIC That Distinguishes Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae
Authors: Tamma Pranita D. , Huang Yanjie , Opene Belita N. A. , Simner Patricia J.
Published: August 2016

Carbapenemase-producing (CP)
Enterobacteriaceae
are largely responsible for the rapid spread of carbapenem-resistant
Enterobacteriaceae
(CRE). Distinguishing CP-CRE from non-CP-CRE has important infection control implications. In a cohort of 198 CRE isolates, for isolates that remained susceptible or intermediate to some carbapenem antibiotics, an ertapenem MIC of 0.5 μg/ml and meropenem, imipenem, and doripenem MICs of 2 μg/ml were best able to distinguish CP-CRE from non-CP-CRE isolates.
First Report of the Globally Disseminated IncX4 Plasmid Carrying the
mcr-1
Gene in a Colistin-Resistant Escherichia coli Sequence Type 101 Isolate from a Human Infection in Brazil
Authors: Fernandes Miriam R. , McCulloch John A. , Vianello Marco A. , Moura Quézia , Pérez-Chaparro Paula J. , Esposito Fernanda , Sartori Luciana , Dropa Milena , Matté Maria H. , Lira Débora P. A. , Mamizuka Elsa M. , Lincopan Nilton
Published: August 2016

A colistin-resistant
Escherichia coli
strain was recovered from a patient with a diabetic foot infection in Brazil. Whole-genome analysis revealed that the
E. coli
isolate belonged to the widespread sequence type (ST) 101 and harbored the
mcr-1
gene on an IncX4 plasmid that was highly similar to
mcr-1
-bearing IncX4 plasmids that were recently identified in
Enterobacteriaceae
from food, animal, and human samples recovered on different continents. These results suggest that self-transmissible IncX4-type plasmids may represent promiscuous plasmids contributing to the intercontinental spread of the
mcr-1
gene.
Gel-Entrapped Staphylococcus aureus Bacteria as Models of Biofilm Infection Exhibit Growth in Dense Aggregates, Oxygen Limitation, Antibiotic Tolerance, and Heterogeneous Gene Expression
Authors: Pabst Breana , Pitts Betsey , Lauchnor Ellen , Stewart Philip S.
Published: August 2016

An experimental model that mimicked the structure and characteristics ofin vivobiofilm infections, such as those occurring in the lung or in dermal wounds where no biomaterial surface is present, was developed. In these infections, microbial biofilm forms as cell aggregates interspersed in a layer of mucus or host matrix material. This structure was modeled by filling glass capillary tubes with an agarose gel that had been seeded withStaphylococcus aureusbacteria and then incubating the gel biofilm in medium for up to 30 h. Confocal microscopy showed that the bacteria formed in discrete pockets distributed throughout the gel matrix. These aggregates enlarged over time and also developed a size gradient, with the clusters being larger near the nutrient- and oxygen-supplied interface and smaller at greater depths. Bacteria entrapped in gels for 24 h grew slowly (specific growth rate, 0.06 h−1) and were much less susceptible to oxacillin, minocycline, or ciprofloxacin than planktonic cells. Microelectrode measurements showed that the oxygen concentration decreased with depth into the gel biofilm, falling to values less than 3% of air saturation at depths of 500 μm. An anaerobiosis-responsive green fluorescent protein reporter gene for lactate dehydrogenase was induced in the region of the gel where the measured oxygen concentrations were low, confirming biologically relevant hypoxia. These results show that the gel biofilm model captures key features of biofilm infection in mucus or compromised tissue: formation of dense, distinct aggregates, reduced specific growth rates, local hypoxia, and antibiotic tolerance.
The Synergistic Effect of Azoles and Fluoxetine against Resistant Candida albicans Strains Is Attributed to Attenuating Fungal Virulence
Authors: Gu Wenrui , Guo Dongmei , Zhang Liuping , Xu Dongmei , Sun Shujuan
Published: August 2016

This study evaluated the synergistic effects of the selective serotonin reuptake inhibitor, fluoxetine, in combination with azoles against
Candida albicans
both
in vitro
and
in vivo
and explored the underlying mechanism. MICs, sessile MICs, and time-kill curves were determined for resistant
C. albicans
.
Galleria mellonella
was used as a nonvertebrate model for determining the efficacy of the drug combinations against
C. albicans
in vivo
. For the mechanism study, gene expression levels of the
SAP
gene family were determined by reverse transcription (RT)-PCR, and extracellular phospholipase activities were detected
in vitro
by the egg yolk agar method. The combinations resulted in synergistic activity against
C. albicans
strains, but the same effect was not found for the non-
albicans Candida
strains. For the biofilms formed over 4, 8, and 12 h, synergism was seen for the combination of fluconazole and fluoxetine. In addition, the time-kill curves confirmed the synergism dynamically. The results of the
G. mellonella
studies agreed with the
in vitro
analysis. In the mechanism study, we observed that fluconazole plus fluoxetine caused downregulation of the gene expression levels of
SAP1
to
SAP4
and weakened the extracellular phospholipase activities of resistant
C. albicans
. The combinations of azoles and fluoxetine showed synergistic effects against resistant
C. albicans
may diminish the virulence properties of
C. albicans
.
Isolated brain metastasis from a small renal mass
Authors: Wallis Christopher J D , Downes Michelle R , Bjarnason Georg , Satkunasivam Raj
Published: August 2016

The identification of small renal masses is increasing. Active surveillance is a guideline-approved management strategy for select patients with small renal masses. Metastases during the observation of small renal masses are uncommon, and no cases of brain metastasis have been reported. We report the case of a 73-year-old man who presented with tonic–clonic seizures as the result of a brain metastasis from a small renal mass (3.5 cm in maximal dimension). Treatment with whole brain radiotherapy was undertaken successfully. The patient will undergo surveillance with consideration for systemic therapy at the time of progression.
Drag load on end-bearing piles in collapsible soil due to inundation
Authors: Mashhour Ibrahim , Hanna Adel
Published: August 2016

Collapsible soils may experience sudden and excessive settlement when inundated. The use of pile foundations that penetrate the collapsible soil layer to reach a firm stratum is widely used in practice. However, when the ground is inundated, large and sudden settlement of the surrounding soil may take place, causing negative skin friction on the pile’s shaft, which may lead to catastrophic failure. In the literature, research dealing with negative skin friction for piles in collapsible soil is lagging due to the complexity of modeling collapsible soil analytically. Alternatively, results of sophisticated experimental investigation may produce valuable information to predict the negative skin friction and accordingly the drag load on these piles. This paper presents the results of an experimental investigation on a single end-bearing pile in collapsible soil. The investigation is tailored to measure the soil collapse before and during inundation and the associated drag load on the pile. The theory proposed by Hanna and Sharif in 2006 for predicting negative skin friction on piles due to consolidation of the surrounding soft clay was extended to predict the negative skin friction for these piles in collapsible soils. A proposed design procedure is presented.