bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the application of Kaizen principles in Indian small-scale industry
Authors: Arya Amit Kumar , Choudhary Suraj
Published: October 2015

Purpose

– This study aims to represent Kaizen implementation in a machine vice manufacturing company. Kaizen has shown tremendous impacts on the production techniques and lead times. A large number of small-scale industries have shown their existence in India. It has been difficult for small industries to survive due to tough competition among them. All are facing problems like low production and poor-quality products.

Design/methodology/approach

– The methodology applied to implement Kaizen in Indian small-scale industry. Fishbone diagrams have been used to represent cause and effects. The result has been shown as savings in terms of money and time.

Findings

– Inventory access time is reduced up to 87 per cent and total distance travelled and total time taken by product is reduced up to 43.75 and 46.08 per cent, respectively. A habit to maintain a clean workplace has been developed in workers.

Research limitations/implications

– ISO could be integrated with Kaizen for more improvements.

Practical implications

– The paper should assist those practitioners and consultants who have the desire to understand a better way of Kaizen implementation in small-scale industries of India.

Originality/value

– This paper yields lots of values for practitioners to understand the need, impacts and significance of Kaizen implementation in small-scale industries of India. Also, it bridges the gap between theory and practice of Kaizen implementation in real working conditions in Indian industries.
Lean initiative practice for supplier developments in Philippines
Authors: Kim Song-Kyoo
Published: October 2015

Purpose

– The purpose of the paper is to demonstrate how Toyota deploys Lean Manufacturing and Toyota Production System (TPS) for their automotive parts’ suppliers in Philippines based on the case study and the literature review.

Design/methodology/approach

– The methods to better understand how Toyota donates Lean Manufacturing to develop their suppliers include to review the general Lean thinking process and tools and study in depth the selected Lean manufacturing tools that are directly related with Toyota supplier development and to show the actual implementations base in the case of the supplier of Toyota in Philippines.

Findings

– The result of the case study shows how Toyota donates their Lean manufacturing (TPS) methods to the suppliers. There are several procedures and various tools for the Lean process. But one procedure within the process and only some of the Lean tools are suitable for supplier development. The case shows that all improvements (Kaizen) during the Lean implementation should be directly intertwined onsite (Genba) and just a small amount of the Lean tools is needed in real-world situations. In other words, the consultation of the Lean implementation might not require the full package of the Lean implementations. More importantly, the consultations of the Lean implementation without deeply understanding the onsite are useless.

Research limitations/implications

– The project for the Lean deployment for supplier implementation is targeted to understand the full procedure from the start to the end, but the case in this paper is only covering the setup phase. As the suppliers of Toyota, there are additional parts to be implemented (i.e. shipping management), but it is not covered in this paper.

Originality/value

– There are some researches about Lean implementation framework, and only few cases deal with the actual Lean implementations. But the case about the Lean implementation of supplier development initiation which aligned with the Toyota Company is unique.
Sustainable property development by Malaysian property companies
Authors: Razali Muhammad Najib , Mohd Adnan Yasmin
Published: October 2015

Purpose

– The concept of sustainability has become increasingly essential to property development, especially in recent years. The purpose of this paper is to assess the level of sustainability practices among listed property companies in Malaysia.

Design/methodology/approach

– Using content analysis, company websites and annual reports, the level of sustainable practices among property companies in Malaysia will be examined and assessed. The paper will also rigorously assess the sustainability strategies employed by using an attributes scorecard, which takes into account several attributes concerning sustainability issues.

Findings

– The findings have showed sustainable property development concept among listed property companies can be categorised as low level, although this is increasing.

Originality/value

– Given the increasing significance of sustainability issues – especially in property development – this paper provides a more informed investment decision strategies regarding the implementation of the sustainability concept in property portfolio; a consideration that has increasingly come into focus amongst international property actors.
Identification of two essential aspartates for polymerase activity in parainfluenza virus L protein by a minireplicon system expressing secretory luciferase
Authors: Matsumoto Yusuke , Ohta Keisuke , Yumine Natsuko , Goto Hideo , Nishio Machiko
Published: October 2015

Gene expression of nonsegmented negative‐strand RNA viruses (nsNSVs) such as parainfluenza viruses requires the RNA synthesis activity of their polymerase L protein; however, the detailed mechanism of this process is poorly understood. In this study, a parainfluenza minireplicon assay expressing secretory Gaussia luciferase (Gluc) was established to analyze large protein (L) activity. Measurement of Gluc expression in the culture medium of cells transfected with the minigenome and viral polymerase components enabled quick and concise calculation of L activity. By comparing the amino acid sequences in conserved region III (CRIII), a putative polymerase‐active domain of the L protein, two strictly conserved aspartates were identified in all families of nsNSV. A series of L mutants from human parainfluenza virus type 2 and parainfluenza virus type 5 showed that these aspartates are necessary for reporter gene expression. It was also confirmed that these aspartates are important for the production of viral mRNA and antigenome cRNA, but not for a polymerase‐complex formation. These findings suggest that these two aspartates are key players in the nucleotidyl transfer reaction using two metal ions.
An insect ecosystem engineer alleviates drought stress in plants without increasing plant susceptibility to an above‐ground herbivore
Authors: Johnson Scott N. , Lopaticki Goran , Barnett Kirk , Facey Sarah L. , Powell Jeff R. , Hartley Susan E.
Published: October 2015

Climate change models predict more extreme rainfall patterns, ranging from droughts to deluges, which will inevitably affect primary productivity in many terrestrial ecosystems. Insects within the ecosystem, living above‐ and below‐ground, may modify plant responses to water stress. For example, some functional groups improve soil conditions via resource provision, potentially alleviating water stress. Enhanced resource provision may, however, render plants more susceptible to herbivores and negate beneficial effects.

Using a model system, we tested how plants (Brassica oleracea) responded to drought, ambient and increased precipitation scenarios when interacting with both a soil conditioning ecosystem engineer (dung beetles; Bubas bison) and an above‐ground herbivore, the major crop pest diamondback moth (Plutella xylostella).

Dung beetles enhanced soil water retention by 10% and promoted growth in plants subjected to drought by 280%, relieving the impacts of water stress on plants. Under drought conditions, plants grown with dung beetles had c. 30% more leaves and were over twice as tall as those without dung beetles. Dung beetles produced a 2·7‐fold increase in nitrogen content and more than a threefold increase in carbon content of the shoots, though shoot concentrations of nitrogen and carbon were unchanged. Carbon concentrations in roots, however, were increased by dung beetles under both ambient and increased precipitation regimes.

Increased precipitation reduced root and shoot nitrogen concentrations by 16% and 30%, relative to plants under ambient regimes, respectively, most likely due to dilution effects of increased plant growth under increased precipitation. Soil carbon and nitrogen concentrations were largely unaffected.

While dung beetles enhanced plant growth and nitrogen content in plants experiencing drought, the anticipated increase in plant suitability to herbivores did not arise, possibly because shoot nitrogen concentrations and C:N ratio were unaffected.

To our knowledge, this is the first report of an insect ecosystem engineer alleviating the effects of predicted drought events on plants via physical manipulation of the soil matrix. Moreover, their effects did not change plant suitability to an above‐ground herbivore, pointing to potential beneficial role for insect ecosystem engineers in climate change adaptation and crop protection.
Effects of temperature and resource variation on insect population dynamics: the bordered plant bug as a case study
Authors: Johnson Christopher A. , Coutinho Renato M. , Berlin Erin , Dolphin Kimberly E. , Heyer Johanna , Kim Britney , Leung Alice , Sabellon Jamie Lou , Amarasekare Priyanga
Published: October 2015

In species with complex life cycles, population dynamics result from a combination of intrinsic cycles arising from delays in the operation of negative density‐dependent processes (e.g. intraspecific competition) and extrinsic fluctuations arising from seasonal variation in the abiotic environment. Abiotic variation can affect species directly through their life‐history traits and indirectly by modulating the species’ interactions with resources or natural enemies.

We investigate how the interplay between density‐dependent dynamics and abiotic variability affects population dynamics of the bordered plant bug (Largus californicus), a Hemipteran herbivore inhabiting the California coastal sage scrub community. Field data show a striking pattern in abundance: adults are extremely abundant or nearly absent during certain periods of the year, leading us to predict that seasonal forcing plays a role in driving observed dynamics.

We develop a stage‐structured population model with variable developmental delays, in which fecundity is affected by both intraspecific competition and temporal variation in resource availability and all life‐history traits (reproduction, development, mortality) are temperature‐dependent. We parameterize the model with experimental data on temperature responses of life‐history and competitive traits and validate the model with independent field census data.

We find that intraspecific competition is strongest at temperatures optimal for reproduction, which theory predicts leads to more complex population dynamics. Our model predicts that while temperature or resource variability interacts with development‐induced delays in self‐limitation to generate population fluctuations, it is the interplay between all three factors that drive the observed dynamics. Considering how multiple abiotic factors interact with density‐dependent processes is important both for understanding how species persist in variable environments and predicting species’ responses to perturbations in their typical environment.
Additive genetic variance and effects of inbreeding, sex and age on heterophil to lymphocyte ratio in song sparrows
Authors: Losdat Sylvain , Arcese Peter , Sampson Laura , Villar Nacho , Reid Jane M.
Published: October 2015

Physiological traits can influence individual fitness and evolutionary changes in stress‐related physiological traits have been hypothesized to mediate the evolution of life‐history traits and trade‐offs. The hypothesis that such physiological variation could drive ongoing life‐history evolution requires non‐zero additive genetic variance in individual stress‐related physiological traits. However, the magnitude of genetic and environmental components of phenotypic variation in stress‐related physiological traits has not been estimated in fully developed vertebrates under natural environmental conditions.

We used 490 observations of heterophil to lymphocyte (H : L) ratio, one stress‐related physiological trait, collected from 350 fully developed song sparrows (Melospiza melodia) across nine different sampling periods to estimate direct and interacting effects of individual and parental coefficients of inbreeding (f), sampling period, age and sex, and to estimate additive genetic variance and heritability.

Across all nine sampling periods combined, H : L ratio increased with individualf. However, there was a significant individualfby period interaction whereby H : L ratio increased with individualfin two of the nine sampling periods, hence indicating inbreeding depression. H : L ratio was higher (suggesting an increase in baseline stress level) in older individuals, did not differ between males and females and did not vary with parentalf.

A quantitative genetic ‘animal model’ estimated low additive genetic variance in individual H : L ratio. The estimated heritability wash2 = 0·04 and did not differ significantly from zero.

Overall, these results imply that the magnitude of inbreeding depression, as measured through H : L ratio, varies with environmental conditions. In contrast, the low estimated heritability implies relatively low potential for H : L ratio to show an evolutionary response to selection, or hence to mediate the evolution of life‐history trade‐offs.
Transient dynamics reveal the importance of early life survival to the response of a tropical tree to harvest
Authors: Gaoue Orou G.
Published: October 2015

Exploitation of non‐timber forest products can contribute to the alleviation of poverty. However, overexploitation can also lead to species decline. Studies on the sustainability of harvest often use stationary population growth rates to assess harvesting effects. For such frequently harvested systems, transient analysis can provide new insights into the response of populations to harvest.

To test the prediction that the effect of harvest differs between transient and asymptotic phases, I used four years of demographic data to compare the impact of harvesting bark and foliage on the short‐ and long‐term dynamics of African dry zone Mahogany Khaya senegalensis in West Africa.

The effect of harvest was stronger in the short term than in the long term, particularly in the moist region. Patterns of transient elasticities also differed from the elasticities of long‐term growth rates to perturbation of vital rates. Survival at early life stages was more important for short‐term dynamics than for long‐term population dynamics.

Synthesis and applications. This study illustrates that using the asymptotic growth rates to assess the impact of harvest may underestimate the short‐term effects of harvest. Short‐term management plans based on the elasticity analysis of long‐term growth rates will be suboptimal given the relative importance of the survival of non‐reproductive stages for population dynamics in the near term. Managers should use results from elasticity analysis of both long‐term and short‐term population dynamics to develop more realistic management plans.
Quantifying how short‐term environmental variation leads to long‐term demographic responses to climate change
Authors: Shriver Robert K.
Published: October 2015

Climate change is expected to alter not only year‐to‐year variation in climate but also aspects of within‐year variation, such as the length of the intervals between rainfall events and the duration of heat waves. Yet we still have a poor understanding of how intra‐annual climate variability and individual weather events alter key vital rates (e.g. individual growth, reproduction and survival) that in part determine population dynamics.

Traditionally, ecologists have accounted for this variability across long time periods by attempting to correlate annual vital rates with measures of within‐year variability (e.g. the coefficient of variation) to match the scale at which demographic data are collected. An alternative to this aggregate approach is to use within‐season yet still relatively infrequent censuses in a probabilistic framework to determine the most likely way that vital rates respond to shorter‐term variation in the environment, and how these short‐term changes cumulatively lead to the observed yearly vital rates.

Here, I present an approach for inferring daily responses of vital rates to short‐term weather variability, and apply it to understand how five species of summer annual plants in the Chihuahuan Desert will respond to climate change.

Vital rate models reveal that species differ in their responses to above‐ and below‐average conditions, but generally fall into two life histories: (i) species that have fast growth on favourable days, but also experience higher mortality on less favourable days, and (ii) species that have slower growth in the same conditions but lower mortality. Results show that the expected rainfall changes in the Chihuahuan Desert (more late, cool season rainfall and less frequent, more intense rainfall events) could reduce growth and increase mortality of all summer annual plants.

Synthesis. My study shows that vital rates can change in response to short‐term variability even when the total amount of rainfall and average temperature, common covariates in demographic models, remain constant. Accounting for changes in short‐term environmental variation in climate change predictions will likely be important in systems with considerable environmental variation between censuses. The approach I present here can be widely applied to understand how short‐term variability and individual weather events will alter organism responses to climate change.
Coparents and parenting programmes: do both parents need to attend?
Authors: Huntington Corinne , Vetere Arlene
Published: October 2015

Numerous parents participate in parenting programmes to promote child development, but few programmes consider relationships within family systems. While both parents’ attendance can improve outcomes, both are rarely able to attend, with mothers typically being the participant. The study aims to understand whether changes to parenting practices can occur from one parent's attendance and, if so, what factors promote the non‐attending parent's modified parenting practices. A mixed‐method evaluation was conducted: semi‐structured interviews, surveys and focus groups. In this study, both parents attributed changes to their parenting practices to programme participation. This was facilitated by mothers giving programme information to fathers and positive coparent relationships. Ideally, both parents would attend every session; however, it is posited that this may not always be necessary for promoting positive parenting. Implications to support families are discussed.

Practitioner points

Fathers can be included in parenting interventions through mothers, if the coparents’ relationship is positive.

If practitioners conducted relationship assessments with coparents, necessary delivery modifications could be made to facilitate both parents’ participation.

Alternatively, parenting practitioners could provide couples’ counselling to coparents, either before or during the delivery of parenting interventions.
The Practice of Scenario Planning: An Analysis of Inter‐ and Intra‐organizational Strategizing
Authors: Bowman Gary
Published: October 2015

Strategic activity is often punctuated through the application of strategy tools. Despite widespread use, a lack of understanding exists regarding the impact such tools and their practices have on an organization's strategy process. Of the growing body of research tackling the phenomenon, none appears to extend beyond an intra‐organizational setting. Acknowledging the importance of multi‐organizational partnerships, particularly in the public sector, in this paper an attempt is made to help fill this void through examining the application and effect of a scenario planning process at an inter‐organizational level. Conceptualizing scenario planning as a practice of simplexity, where complexity of thought combines with simplicity of action, an in‐depth, longitudinal case study is used to demonstrate the importance and interaction of sensemaking, storytelling and organizing in creating meaning within strategizing activities at the inter‐organizational level. However, also demonstrated is the relative weakness of the output of the scenario planning process − the stories − as a boundary object capable of transferring knowledge and meaning to the intra‐organizational level. Through empirical and theoretical integration a model is developed presenting the flow of practices and artefacts used in sensemaking within inter‐ and intra‐organizational strategizing.
WORK, INCOME SUPPORT, AND CRIME IN THE DUTCH WELFARE STATE: A LONGITUDINAL STUDY FOLLOWING VULNERABLE YOUTH INTO ADULTHOOD
Authors: VERBRUGGEN JANNA , APEL ROBERT , VAN DER GEEST VICTOR R. , BLOKLAND ARJAN A. J.
Published: October 2015

Life‐course criminological research has consistently suggested that employment can reduce criminal behavior. However, it is unclear whether the financial aspects of employment or the social control that inheres in employment best explains the relationship between employment and reduced offending. By using longitudinal information on a sample of men and women (N = 540) who were institutionalized in a Dutch juvenile justice institution in the 1990s, this study examines the effects of employment as well as the different types of income support on crime. Random‐ and fixed‐effects models show that for men, both work and income support are associated with a reduction in the rate of offending. For women, however, although employment is correlated with a lower offending rate, receiving income support, and in particular disability benefits, is correlated with a higher offending rate. The findings support both theories that stress the financial motivation for crime as well as theories that emphasize the importance of informal social control for reducing offending.
Comparison between Folin‐Ciocalteu and Prussian Blue Assays to Estimate The Total Phenolic Content of Juices and Teas Using 96‐Well Microplates
Authors: Margraf Tiago , Karnopp Ariadne Roberto , Rosso Neiva Deliberali , Granato Daniel
Published: October 2015

Folin‐Ciocalteu colorimetric assay (FC) is the most widely used assay to estimate the total phenolic content in foods, beverages, herbs and other plant extracts, but many chemical compounds may act as interfering agents, producing inaccurate estimations of the real concentration of phenolic compounds in the matrix. Based on this limitation, the objective of this study was to compare, quantitatively, the Folin‐Ciocalteu and Prussian Blue (PB) assays in estimating the total phenolic content in purple grape juices (n = 20; Vitis labrusca L.) and teas (n = 25) from different botanical origins using 96‐well microplates. PB assay presented a low limit of detection (PB = 0.27 mg/L; FC = 0.25 mg/L) and quantification (PB = 0.92 mg/L; FC = 0.82 mg/L), showing its suitability in screening the total phenolic content in grape juices and teas. FC and PB assays presented a high association (P < 0.0001) for teas (r = 0.887) and grape juices (r = 0.923). The advantages of PB over FC assay are its simplicity, low time consumption (15 min reaction as compared to 60 min reaction for the FC assay), lower usage of reagents (solutions are prepared in a mM base), and higher selectivity. Additionally, PB assay was proven to be reproducible and repeatable and, therefore, may be used as an alternative to FC assay.
Towards a mechanistic understanding of the synergistic effects of harvesting timber and non‐timber forest products
Authors: Gaoue Orou G. , Ngonghala Calistus N. , Jiang Jiang , Lelu Maud
Published: October 2015

Classic theories of resource harvest assume logistic growth and incorporate harvest through an additional loss term. This methodology has been applied successfully in forest products harvesting such as timber logging. However, modelling harvest through a loss term is not appropriate for non‐timber forest products (NTFP) since harvesting in this case does not always require the complete removal of individual plants.

Empirical evidence suggest that NTFP harvest affects plant population growth rates. Additionally, timber and NTFP harvest can have synergistic effects on population dynamics. We develop and analyse a simple model that incorporates non‐lethal harvest implicitly through the population growth rate of plants and lethal harvest explicitly through permanent removal of whole plants, with additional synergistic effects on population growth rate. To capture transient dynamics, we model the growth rate of plants explicitly as a dynamic variable affected by harvesting.

Transient dynamics results indicate that populations have delayed response to discrete harvesting. We demonstrate exactly how the sustainability of lethal harvest, non‐lethal harvest or both types of harvests depends on the demographic effect of each type of harvest on the population growth rate.

Finally, we identify a threshold parameter, such that combined lethal and non‐lethal harvest results in plant population sustainability when1 and extinction when1.
Cell‐specific ablation in the testis: what have we learned?
Authors: Smith L. B. , O'Shaughnessy P. J. , Rebourcet D.
Published: October 2015

Testicular development and function is the culmination of a complex process of autocrine, paracrine and endocrine interactions between multiple cell types. Dissecting this has classically involved the use of systemic treatments to perturb endocrine function, or more recently, transgenic models to knockout individual genes. However, targeting genes one at a time does not capture the more wide‐ranging role of each cell type in its entirety. An often overlooked, but extremely powerful approach to elucidate cellular function is the use of cell ablation strategies, specifically removing one cellular population and examining the resultant impacts on development and function. Cell ablation studies reveal a more holistic overview of cell–cell interactions. This not only identifies important roles for the ablated cell type, which warrant further downstream study, but also, and importantly, reveals functions within the tissue that occur completely independently of the ablated cell type. To date, cell ablation studies in the testis have specifically removed germ cells, Leydig cells, macrophages and recently Sertoli cells. These studies have provided great leaps in understanding not possible via other approaches; as such, cell ablation represents an essential component in the researchers’ tool‐kit, and should be viewed as a complement to the more mainstream approaches to advancing our understanding of testis biology. In this review, we summarise the cell ablation models used in the testis, and discuss what each of these have taught us about testis development and function.
Genetic aetiology of ophthalmological manifestations in children – a focus on mitochondrial disease‐related symptoms
Authors: Widgren Paula , Hurme Anri , Falck Aura , Keski‐Filppula Riikka , Remes Anne M , Moilanen Jukka , Majamaa Kari , Kervinen Marko , Uusimaa Johanna
Published: October 2015

Purpose

To investigate the association of mutations in the mitochondrial DNA (mtDNA) or nuclear candidate genes with mitochondrial disease‐related ophthalmic manifestations (nystagmus, ptosis, ophthalmoplegia, optic neuropathy and retinopathy) in children.

Methods

A retrospective cohort of children (n = 98) was identified from the medical record files of a tertiary care hospital. The entire mtDNA and nuclear genes POLG1, OPA1 and PEO1 were analysed from the available DNA samples (n = 38). Furthermore, some nuclear candidate genes were investigated based on family history and phenotype. Rare mtDNA mutations were evaluated using in silico predictors and sequence alignment.

Results

Three patients had previously identified mutations in mtDNA that are associated with optic neuropathy (in MT‐ND6 and MT‐ND1) and nystagmus (in tRNA Arg). Nine rare mutations in MT‐ATP6 were identified in seven patients, of whom four manifested with retinopathy and three had clusters of MT‐ATP6 mutations. Nuclear PEO1 and OPA1 were unchanged in all samples, but a patient with nystagmus had a heterozygous POLG1 mutation. The analysis of nuclear candidate genes revealed mutations in NDUF8 (patient with nystagmus), TULP1 (patient with optic neuropathy, nystagmus and retinopathy) and RP2 (patient with retinopathy) genes.

Conclusions

Children with retinopathy, nystagmus or optic neuropathy, especially together with developmental delay or positive family history, should be considered for mitochondrial disease. MT‐ATP6 should be taken into account for children with retinopathy of unknown aetiology.
Altered Loyalties of Neuronal Markers in Cultured Slices of Resected Human Brain Tissue
Authors: Verwer Ronald W. H. , Sluiter Arja A. , Balesar Rawien A. , Baayen Johannes C. , Speijer Dave , Idema Sander , Swaab Dick F.
Published: October 2015

Organotypic cultures from normal neocortical tissue obtained at epilepsy surgery show a severe injury response. This response involves both neuronal degeneration and the proliferation of reactive cells. A salient feature of the reactive cells is the co‐expression of microglial and astrocytic markers. Surprisingly, the reactive cells also began to express neuronal markers Tubulin βIII and MAP2 adding to the confusion about their origin. Concomitant with their appearance in reactive cells MAP2 and Tubulin βIII expression disappeared from neurons. While NeuN expression decreased significantly, it did not entirely disappear from many neurons. Moreover, it was not observed in reactive cells, showing that NeuN is a reliable marker of neurons.
Identification of a resveratrol tetramer as a potent inhibitor of hepatitis C virus helicase
Authors: Lee Sungjin , Yoon Kee Dong , Lee Myungeun , Cho Yoojin , Choi Gahee , Jang Hongje , Kim BeomSeok , Jung Da‐Hee , Oh Jin‐Gyo , Kim Geon‐Woo , Oh Jong‐Won , Jeong Yong‐Joo , Kwon Ho Jeong , Bae Soo Kyung , Min Dal‐Hee , Windisch Marc P , Heo Tae‐Hwe , Lee Choongho
Published: October 2015

Background and Purpose

Hepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti‐HCV activity and have elucidated its mode of antiviral action.

Experimental Approach

Luciferase reporter and real‐time RT‐PCR assays were used to measure HCV replication. Western blot, fluorescence‐labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism.

Key Results

A resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC50 = 6 nM) with relatively low cytotoxicity (EC50 >10 μM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B‐resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC50 = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations.

Conclusion and Implications

Vitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products.
Mechanisms by which the thiazolidinedione troglitazone protects against sucrose‐induced hepatic fat accumulation and hyperinsulinaemia
Authors: Martins Fátima O , Delgado Teresa C , Viegas Joana , Gaspar Joana M , Scott Donald K , O'Doherty Robert M , Paula Macedo M , Jones John G
Published: October 2015

Background and Purpose

Thiazolidinediones (TZD) are known to ameliorate fatty liver in type 2 diabetes. To date, the underlying mechanisms of their hepatic actions remain unclear.

Experimental Approach

Hepatic triglyceride content and export rates were assessed in 2 week high‐sucrose‐fed Wistar rats treated with troglitazone and compared with untreated high‐sucrose rodent controls. Fractional de novo lipogenesis (DNL) contributions to hepatic triglyceride were quantified by analysis of triglyceride enrichment from deuterated water. Hepatic insulin clearance and NO status during a meal tolerance test were also evaluated.

Key Results

TZD significantly reduced hepatic triglyceride (P < 0.01) by 48%, decreased DNL contribution to hepatic triglyceride (P < 0.01) and increased postprandial non‐esterified fatty acids clearance rates (P < 0.01) in comparison with the high‐sucrose rodent control group. During a meal tolerance test, plasma insulin AUC was significantly lower (P < 0.01), while blood glucose and plasma C‐peptide levels were not different. Insulin clearance was increased (P < 0.001) by 24% and was associated with a 22% augmentation of hepatic insulin‐degrading enzyme activity (P < 0.05). Finally, hepatic NO was decreased by 24% (P < 0.05).

Conclusions

Overall, TZD show direct actions on liver by reducing hepatic DNL and increasing hepatic insulin clearance. The alterations in hepatic insulin clearance were associated with changes in insulin‐degrading enzyme activity, with possible modulation of NO levels.
Long‐term Spatial Changes in the Distribution of the Brazilian Atlantic Forest
Authors: Ledru Marie‐Pierre , Montade Vincent , Blanchard Grégoire , Hély Christelle
Published: October 2015

The aim of this study is to represent simultaneously changes in the spatial distribution of the Atlantic forest during the last 17,000 years. To characterize such changes, here we focused on three different forest physiognomies, evergreen, semi‐deciduous, and Araucaria, and we provide a list of indicator taxa for each class retrieved from the original published datasets. A review of the published fossil pollen records allowed us to classify regional behaviors in three main areas of distribution, north of 15°S, between 15° and 23°S and south of 23°S latitude that correspond to three climatic geographical barriers. Statistical probability density function method was used to illustrate changes in forest physiognomies throughout the three distribution areas. We show that the three modern barriers also functioned through the past. Asynchronous patterns of forest physiognomies are linked to an antiphasing pattern of monsoon precipitation between the northern and central area, whereas in the southern area, it is linked to the frequency and intensity of the polar advection in the subtropics. Our results attest to strong climate forcing on forest distribution between the late glacial and the interglacial period. They call into question the common reference to the last glacial maximum as a major (and sometimes as the only) driver of forest‐related vicariance and genetic diversity patterns, but suggest that instead, orbital cycles were the main drivers of the successive expansion/contraction of the Atlantic forest throughout the Quaternary.
The inferior impact of antibody‐mediated rejection on the clinical outcome of kidney allografts that develop de novo thrombotic microangiopathy
Authors: Wu Kaiyin , Budde Klemens , Schmidt Danilo , Neumayer Hans‐Hellmut , Lehner Lukas , Bamoulid Jamal , Rudolph Birgit
Published: October 2015

Background

Antibody‐mediated rejection (AMR) can induce and develop thrombotic microangiopathy (TMA) in renal allografts. A definitive AMR (dAMR) co‐presents three diagnostic features. A suspicious AMR (sAMR) is designated when one of the three features is missing.

Methods

Thirty‐two TMA cases overlapping with AMR (AMR+ TMA) were studied, which involved 14 cases of sAMR+ TMA and 18 cases of dAMR+ TMA. Thirty TMA cases free of AMR features (AMR− TMA) were enrolled as control group.

Results

The ratio of complete response to treatment was similar between AMR− TMA and AMR+ TMA group (23.3% vs. 12.5%, p = 0.33), or between sAMR+ TMA and dAMR+ TMA group (14.3% vs. 11.1%, p = 0.79). At eight yr post‐transplantation, the death‐censored graft survival (DCGS) rate of AMR− TMA group was 62.8%, which was significantly higher than 28.0% of AMR+ TMA group (p = 0.01), but similar between sAMR+ TMA and dAMR+ TMA group (30.0% vs. 26.7%, p = 0.92). Overall, the intimal arteritis and the broad HLA (Human leukocyte antigens) mismatches were closely associated with over time renal allograft failure.

Conclusion

The AMR+ TMA has inferior long‐term graft survival, but grafts with sAMR+ TMA or dAMR+ TMA have similar characteristics and clinical courses.
The incidence and risk factors for deep vein thrombosis after kidney transplantation in Korea: single‐center experience
Authors: Ahn Sanghyun , Kim Mi‐Hyeong , Jun Kang‐Woong , Hwang Jeong‐Kye , Park Soon‐Chul , Moon In‐Sung , Kim Ji‐Iil
Published: October 2015

Background

The incidence of deep vein thrombosis (DVT) after kidney transplantation (KT) and the risk factors are still unknown in Korean patients. Determining the need for appropriate DVT prophylaxis is difficult when considering the low incidence of DVT in the Asian population. The aim of this study was to investigate the incidence of DVT occurring 3 months after KT, the DVT occurrence pattern, and risk factors in Korean patients.

Methods

Data from a total of 393 patients who underwent KT from November 2009 to December 2012 were analyzed. Color duplex ultrasonography was used for the diagnosis or screening of DVT in all patients pre‐operatively and on post‐operative days 7, 14, 28, and 90.

Results

The cumulative 3‐month incidence of DVT after KT was 4.6%, and there was one symptomatic DVT. Patients with DVT were older than those without DVT at the time of transplantation (52.8 vs. 44.6, p < 0.001). According to univariate and multivariate analysis, older age was identified as a risk factor for DVT at the time of transplantation, whereas history of DVT did not reach statistical significance. There were no deaths related to DVT or pulmonary embolism.

Conclusions

Pharmacological prophylaxis after KT is not necessary because of the low incidence of DVT in Korean patients, and instead, we suggest that long‐term mechanical prophylaxis of at least 3 months can be a suitable option. Patients older than 50 years of age have a higher risk of developing DVT, and careful observation is needed in these patients.
Electric crows: powerlines, climate change and the emergence of a native invader
Authors: Cunningham S. J. , Madden C. F. , Barnard P. , Amar A.
Published: October 2015

Aim

Climate change and other anthropogenic global change drivers act in complex, mutually exacerbating ways to alter the abundance and distribution of species. In South Africa, pied crows Corvus albus have increased in numbers and range in recent decades. Popular opinion links these changes to urbanisation and infrastructure development, but there has been no empirical test of this idea. We aimed to clarify the drivers of pied crow population changes in South Africa.

Location

South Africa.

Methods

We used publicly available long‐term datasets, the Southern African Bird Atlas Project and University of Delaware Gridded Climate Database, and spatial data from government bodies, to assess relationships between pied crow population and range changes, land use, infrastructure, urbanisation and climate change.

Results

Pied crow numbers have increased significantly in the past three decades, but rate of increase varied geographically, with crows declining in the northeast and increasing in the south‐west of South Africa. Pied crow population changes were strongly correlated with climate change. Crows have benefited most from climate warming in the shrubland biomes of south‐western South Africa. Pied crows are tree nesters, and within these shrublands, there is a strong positive relationship between the rate of population increase and the density of powerline infrastructure, which may facilitate pied crows’ increase by providing nesting sites.

Main conclusions

Pied crow numbers have increased in response to climate warming, with their spread facilitated by electrical infrastructure in south‐western South Africa, providing a clear example of compound influence of multiple global change drivers promoting a significant change in species range and reporting rate. Pied crows are generalist predators and there is popular concern about their ecological impact in areas where increases have occurred. We highlight the importance of understanding the ecosystem‐level implications of increased numbers of pied crows in South Africa's shrubland biomes.
Phylogenetic analysis of niche divergence reveals distinct evolutionary histories and climate change implications for tropical carnivorous pitcher plants
Authors: Schwallier Rachel , Raes Niels , de Boer Hugo J. , Vos Rutger A. , van Vugt Rogier R. , Gravendeel Barbara
Published: October 2015

Aim

To analyse the underpinnings of historical drivers of diversity and their contributions to current distributions and future roles in a changing climate, we studied the relationship between ecological niche divergence and phylogenetic signal in tropical carnivorous pitcher plants.

Location

Southeast Asia.

Methods

Estimates of realized ecological niches were reconstructed and plotted along a newly created multilocus molecular phylogeny. Phylogenetic signal was analysed by comparisons of calculated phylogenetic relatedness with ecological niche divergence. Current and projected future potentially suitable habitats were mapped for several species of plants with variable evolutionary histories and distributions.

Results

Highland and lowland species had distinct phylogenetic signals. Higher altitude species had significantly lower molecular divergence as compared with the lowland species, yet ecological niches with less overlap. When projected onto a future climate scenario, highland species lose a greater amount of potentially suitable habitat compared to lower altitude species, and the majority of studied higher altitude species will face an overall loss of future suitable habitat.

Main conclusion

We conclude that distinct phylogenetic signals not only unravel differing evolutionary histories but also show that the implications of species' tolerances to future changing climate vary. Over the past million years, historical climate change shaped the differing evolution and ecological niches of highland and lowland tropical pitcher plant species. Rapid, recent radiations of the higher altitude species are reflected in limited molecular divergence, which is in sharp contrast with the more gradually evolved and genetically distinct lower altitude species in our study. Our projections for future potentially suitable habitats show that on‐going climate shifts will have detrimental effects on especially the higher altitude species due to a narrower niche tolerance and dramatic loss of potentially suitable habitat.
Left ventricular outflow tract gradient is associated with reduced capillary density in hypertrophic cardiomyopathy irrespective of genotype
Authors: Güçlü Ahmet , Happé Chris , Eren Seyma , Korkmaz Ibrahim H. , Niessen Hans W. M. , Klein Patrick , van Slegtenhorst Marjon , Schinkel Arend F. , Michels Michelle , van Rossum Albert C. , Germans Tjeerd , van der Velden Jolanda
Published: October 2015

Background

Coronary microvascular dysfunction (CMD) is an important feature of hypertrophic cardiomyopathy (HCM), which contributes negatively to symptoms and long‐term outcome. Previous in vivo imaging studies in HCM suggest that left ventricular outflow tract (LVOT) gradient and genetic status are important contributors to CMD. CMD may be caused by reduced capillary density. Here, we investigated whether a reduction in capillary density is related to genetic status or LVOT gradient severity in an in vitro study of HCM cardiac samples.

Methods

Using immunofluorescence microscopy, we analysed capillaries (Cap) and cardiomyocytes (CM) in myectomy specimens from 18 HCM patients with maximum left ventricular (LV) wall thickness ≥15 mm. All subjects exhibited significant LVOT obstruction, necessitating septal myectomy. In addition, control myocardium from the LV septal wall was collected at autopsy of 6 individuals that suffered a noncardiac death.

Results

CM area was higher in patients with HCM compared to controls. Capillary density was significantly lower in patients with HCM compared with controls (1425 ± 262 vs. 2543 ± 509 Cap/mm2, P < 0·001), as was the number of Cap per CM corrected for CM area (2·2 ± 0·5 vs. 4·2 ± 0·9 Cap/CM area, P < 0·001). Capillary density did not differ between genotype‐negative and genotype‐positive HCM patients at similar resting LVOT gradients. A significant correlation was present between resting LVOT gradient and CM area (r = 0·73, P < 0·001), capillary density (r = −0·74, P < 0·001) and the number of Cap per CM corrected for CM area (r = −0·82, P < 0·001).

Conclusions

Our data indicate that LVOT gradient, rather than genetic status, is associated with reduced capillary density in HCM.
A new rescue regimen with plasma exchange and rituximab in high‐risk membranous glomerulonephritis
Authors: Müller‐Deile Janina , Schiffer Lena , Hiss Marcus , Haller Hermann , Schiffer Mario
Published: October 2015

Background

Even though current treatment guidelines for idiopathic membranous glomerulonephritis (iMGN) exist, many questions regarding an optimal therapy remain unanswered. Complete remission cannot be achieved in all patients; relapses occur, in some cases frequently, and side effects from the immunosuppressive therapy are common. Therapeutic options in high‐risk patients not responding to standard immunosuppressive therapies are limited. Recent research reveals that the human M‐type phospholipase A2 receptor (PLA2R) is a causative factor in iMGN that parallels clinical disease activity. However, in some patients, this correlation is not evident and additional undetermined factors seem to play a role.

Design

We evaluated a new rescue protocol including plasma exchanges (PE) against albumin, intravenous immunoglobulins (IVIGs) and rituximab for 10 patients with a biopsy‐proven diagnosis of iMGN who were therapy‐resistant to all conventional regimens and had a urinary protein to creatinine ratio of more than 10 000 mg/g Crea. We compared this protocol with standard immunosuppressive protocols including monthly alternating prednisolone plus cyclophosphamide (18 patients), cyclosporine plus prednisolone (23 patients) and rituximab alone (eight patients) in a retrospective design.

Results

Our rescue regimen with PE, IVIGs and rituximab achieved partial remission in 90% of patients who had been otherwise refractory to therapy. The mean time to partial remission was 2·1 months. Furthermore, two anti‐PLA2R‐antibody negative patients were also treated with this rescue regimen, achieving partial remission after 1 and 4 months.

Conclusion

A combination of PE, IVIGs and rituximab is a treatment option to consider for high‐risk patients with iMGN who are refractory to conventional therapy.