bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel magnetic resonance technique for characterizing mesoscale structure of trabecular bone
Authors: Nguyen Chantal , Schlesinger Kimberly J. , James Timothy W. , James Kristin M. , Sah Robert L. , Masuda Koichi , Carlson Jean M.
Published: August 2018

Osteoporosis, characterized by increased fracture risk and bone fragility, impacts millions of adults worldwide, but effective, non-invasive and easily accessible diagnostic tests of the disease remain elusive. We present a magnetic resonance (MR) technique that overcomes the motion limitations of traditional MR imaging to acquire high-resolution frequency-domain data to characterize the texture of biological tissues. This technique does not involve obtaining full two-dimensional or three-dimensional images, but can probe scales down to the order of 40 μm and in particular uncover structural information in trabecular bone. Using micro-computed tomography data of vertebral trabecular bone, we computationally validate this MR technique by simulating MR measurements of a ‘ratio metric’ determined from a few
k
-space values corresponding to trabecular thickness and spacing. We train a support vector machine classifier on ratio metric values determined from healthy and simulated osteoporotic bone data, which we use to accurately classify osteoporotic bone.
On the relationship between maxillary molar root shape and jaw kinematics in
Australopithecus africanus
and
Paranthropus robustus
Authors: Kupczik Kornelius , Toro-Ibacache Viviana , Macho Gabriele A.
Published: August 2018

Plio-Pleistocene hominins from South Africa remain poorly understood. Here, we focus on how
Australopithecus africanus
and
Paranthropus robustus
exploited and—in part—partitioned their environment. Specifically, we explore the extent to which first maxillary molar roots (M
1
) are oriented and thus, by proxy, estimate the direction of loads habitually exerted on the chewing surface. Landmark-based shape analysis of M
1
root reconstructions of 26 South African hominins and three East African
Paranthropus boisei
suggest that
A. africanus
may have been able to dissipate the widest range of laterally directed loads.
Paranthropus robustus
and
P. boisei
, despite having overlapping morphologies, differ in aspects of root shape/size, dento-cranial morphologies, microwear textures and C4 food consumption. Hence, while
Paranthropus
monophyly cannot be excluded, equivalence of dietary niche can. The South African hominins occupied distinct ecological niches, whereby
P. robustus
appears uniquely adapted to dissipate antero-posteriorly directed loads.
Genetics of a de novo origin of undifferentiated multicellularity
Authors: Herron Matthew D. , Ratcliff William C. , Boswell Jacob , Rosenzweig Frank
Published: August 2018

The evolution of multicellularity was a major transition in evolution and set the stage for unprecedented increases in complexity, especially in land plants and animals. Here, we explore the genetics underlying a de novo origin of multicellularity in a microbial evolution experiment carried out on the green algaChlamydomonas reinhardtii. We show that large-scale changes in gene expression underlie the transition to a multicellular life cycle. Among these, changes to genes involved in cell cycle and reproductive processes were overrepresented, as were changes toC. reinhardtii-specific and volvocine-specific genes. These results suggest that the genetic basis for the experimental evolution of multicellularity inC. reinhardtiihas both lineage-specific and shared features, and that the shared features have more in common withC. reinhardtii's relatives among the volvocine algae than with other multicellular green algae or land plants.
Kinship influences sperm whale social organization within, but generally not among, social units
Authors: Konrad Christine M. , Gero Shane , Frasier Timothy , Whitehead Hal
Published: August 2018

Sperm whales have a multi-level social structure based upon long-term, cooperative social units. What role kinship plays in structuring this society is poorly understood. We combined extensive association data (518 days, during 2005–2016) and genetic data (18 microsatellites and 346 bp mitochondrial DNA (mtDNA) control region sequences) for 65 individuals from 12 social units from the Eastern Caribbean to examine patterns of kinship and social behaviour. Social units were clearly matrilineally based, evidenced by greater relatedness within social units (meanr= 0.14) than between them (meanr= 0.00) and uniform mtDNA haplotypes within social units. Additionally, most individuals (82.5%) had a first-degree relative in their social unit, while we found no first-degree relatives between social units. Generally and within social units, individuals associated more with their closer relatives (matrix correlations: 0.18–0.25). However, excepting a highly related pair of social units that merged over the study period, associations between social units were not correlated with kinship (p> 0.1). These results are the first to robustly demonstrate kinship's contribution to social unit composition and association preferences, though they also reveal variability in association preferences that is unexplained by kinship. Comparisons with other matrilineal species highlight the range of possible matrilineal societies and how they can vary between and even within species.
Effects of amendments on heavy metal immobilization and uptake by
Rhizoma chuanxiong
on copper and cadmium contaminated soil
Authors: Xie Yanluo , Xiao Kemeng , Sun Yang , Gao Yufeng , Yang Han , Xu Heng
Published: August 2018

An improved method was applied for remediating cadmium and copper co-contaminated soil and reducing the metal concentration in
Rhizoma chuanxiong
. Pot experiments were conducted with six amendments (composed with bentonite, phosphate, humic acid, biochar, sepiolite powder, etc.). The results showed that soil pH, biological activities (soil enzymatic activities and microbial counts) and
R. chuanxiong
biomass were greatly improved with the addition of amendments in all treatments, especially in T3 and T6. Also, amendments effectively decreased the concentration of malondialdehyde and H
2
O
2
in
R. chuanxiong
. In the T3 treatment, the bio-available Cd and Cu in soil were significantly decreased by 0.53 and 0.41 mg kg
−1
, respectively. Meanwhile, the amendment in T3 reduced Cd and Cu accumulation in
R. chuanxiong
about 45.83 and 39.37%, respectively, compared to T0. Moreover, the Fourier transform infrared spectroscopy spectra showed the surface functional groups of every amendment. To conclude, this study offers an effective and environmental method to reduce metal accumulation in
R. chuanxiong
on heavy metal co-contaminated soil.
Novelty and surprise-timing are broadcast by the basal forebrain
Authors: Zhang Kaining , Chen Charles D. , Monosov Ilya E.
Published: August 2018

The basal forebrain (BF) is a principal source of modulation of the neocortex, and is thought to regulate cognitive functions such as attention, motivation, and learning by broadcasting information about the behavioral salience of events. An event can be salient because it is novel, surprising, or associated with reward prediction errors. But to date, the type of salience-related information the BF broadcasts is unclear. Here, we report that many BF neurons display phasic excitatory bursting that rapidly conveys the magnitude, probability, and timing of primary reinforcements. The same BF neurons also discriminate fully expected novel visual objects from familiar objects and respond to object-sequence violations, regardless of their relevance for subsequent behaviors, suggesting that they are not dedicated to signaling information about primary reinforcements. A different group of BF neurons displayed ramping activations that predicted the time of novel and surprising events. Their ramping was highly sensitive to the subjects’ confidence in event timing. Hence, BF neurons signal statistics about time and salience. Their activity may organize cortical computations to facilitate accurate behavioral responses to a diverse set of expected and ongoing events.
An homeotic post-transcriptional network controlled by the RNA-binding protein RBMX
Authors: Zuccotti Paola , Peroni Daniele , Potrich Valentina , Quattrone Alessandro , Dassi Erik
Published: August 2018

Post-transcriptional regulation (PTR) of gene expression is a powerful determinant of protein levels and cellular phenotypes. The 5’ and 3’ untranslated regions of the mRNA (UTRs) mediate this role through sequence and secondary structure elements bound by RNA-binding proteins (RBPs) and noncoding RNAs. While functional regions in the 3’UTRs have been extensively studied, the 5’UTRs are still relatively uncharacterized. To fill this gap, here we used a computational approach based on phylogenetic conservation to identify hyper-conserved elements in human 5’UTRs (5’HCEs). Our assumption, supported by the recovery of functionally characterized elements, was that 5’HCEs would represent evolutionarily stable and hence important PTR sites.

We identified over 5000 short, clustered 5’HCEs occurring in approximately 10% of human protein-coding genes. Among these, homeotic genes were highly enriched. Indeed, 52 of the 258 characterized homeotic genes contained at least one 5’HCE, including members of all four Hox clusters and several other families. Homeotic genes are essential transcriptional regulators. They drive body plan and neuromuscular development, and the role of PTR in their expression is mostly unknown. By integrating computational and experimental approaches we then identified the RBMX RNA-binding protein as the initiator of a post-transcriptional cascade regulating many such homeotic genes. RBMX is known to control its targets by modulating transcript abundance and alternative splicing. Adding to that, we observed translational control as a novel mode of regulation by this RBP.

This work thus establishes RBMX as a versatile master controller of homeotic genes and of the developmental processes they drive.
Metabolic potential of uncultured bacteria and archaea associated with petroleum seepage in deep-sea sediments
Authors: Dong Xiyang , Greening Chris , Rattray Jayne E. , Chakraborty Anirban , Chuvochina Maria , Mayumi Daisuke , Dolfing Jan , Li Carmen , Brooks James M. , Bernard Bernie B. , Groves Ryan A. , Lewis Ian A. , Hubert Casey R.J.
Published: August 2018

The lack of microbial genomes and isolates from the deep seabed means that very little is known about the ecology of this vast habitat. Here, we investigated energy and carbon acquisition strategies of microbial communities from three deep seabed petroleum seeps (3 km water depth) in the Eastern Gulf of Mexico. Shotgun metagenomic analysis revealed that each sediment harbored diverse communities of chemoheterotrophs and chemolithotrophs. We recovered 82 metagenome-assembled genomes affiliated with 21 different archaeal and bacterial phyla. Multiple genomes encoded enzymes for anaerobic oxidation of aliphatic and aromatic compounds, including those of candidate phyla Aerophobetes, Aminicenantes, TA06 and Bathyarchaeota. Microbial interactions are predicted to be driven by acetate and molecular hydrogen. These findings are supported by sediment geochemistry, metabolomics, and thermodynamic modelling. Overall, we infer that deep-sea sediments experiencing thermogenic hydrocarbon inputs harbor phylogenetically and functionally diverse communities potentially sustained through anaerobic hydrocarbon, acetate and hydrogen metabolism.
Quantifying the impact of dengue containment activities using high-resolution observational data
Authors: Rehman Nabeel Abdur , Salje Henrik , Kraemer Moritz U G , Subramanian Lakshminarayanan , Cauchemez Simon , Saif Umar , Chunara Rumi
Published: August 2018

Dengue virus causes over 96 million cases worldwide per year and is ex-panding rapidly in geographic range, especially in urban areas. Containment activities are an essential part of reducing the public health burden caused by dengue, but systematic evidence on the comparative efficacy of activities from the field is lacking. To our knowledge, the effect of containment activities on local (sub-city) scale disease dynamics has never been systematically characterized using empirical containment and case data. We combine data from a comprehensive dengue containment monitoring system with confirmed dengue case data from the local government hospitals to estimate the efficacy of seven common containment activities in two urban areas in Pakistan. We use a modified version of the time series Suspected Infected Recovered frame-work to estimate how the reproductive number, R0, of the outbreak changed in relation to deployment of each containment activity. We also estimate the spatial dependence of cases based on deployment of each containment activity. Both analyses suggest that activities aimed at the adult phase of the mosquito lifecycle have the highest efficacy, with fogging having the largest quantifiable effect in reducing cases immediately after deployment. In examining the efficacy of containment activities contemporaneously deployed in the same locations, results here can guide recommendations for future deployment of resources during dengue outbreaks in urban settings.
Heterogeneity in the respiratory symptoms of patients with mild-moderate COPD
Authors: Johnson Kate M. , Safari Abdollah , Tan Wan C. , Bourbeau Jean , FitzGerald J Mark , Sadatsafavi Mohsen ,   for the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study and the Canadian Respiratory Research Network
Published: August 2018

Background

The burden of symptoms varies markedly between patients with Chronic Obstructive Pulmonary Disease (COPD) and is only weakly correlated with lung function impairment. While heterogeneity in lung function decline and exacerbations have been previously studied, the extent of heterogeneity in symptoms and the factors associated with this heterogeneity are not well understood.

Methods

A sample of the general Canadian population ≥40 years with persistent airflow limitation was followed for up to 3 years. Participants reported whether they experienced chronic coughing, phlegm, wheezing, or dyspnea during visits at 18-month intervals. We used mixed-effect logistic regression models (separately for each symptom) to assess overall heterogeneity in the occurrence of symptoms between individuals, and the proportion of variation in symptom burden explained by lung function versus all other clinical characteristics of participants.

Results

548 participants (54% male, mean age 67 years) contributed 1,086 visits in total, and 82% of patients reported at least one symptom during follow-up. There was substantial heterogeneity in the individual-specific probabilities for the occurrence of symptoms. This heterogeneity was highest for dyspnea and lowest for phlegm (interquartile range of probabilities: 0.15-0.77 and <0.01-0.53, respectively). FEV1 explained 82% of the variation between individuals in the occurrence of phlegm, 26% for dyspnea, 3% for cough, and <0.1% for wheeze. All clinical characteristics of participants (including FEV1) explained between 86% of heterogeneity in the occurrence of phlegm to <1% for wheeze.

Conclusion

There is marked heterogeneity in the burden of respiratory symptoms between COPD patients. The ability of lung function and other commonly measured clinical characteristics to explain this heterogeneity differs between symptoms.
A single cell transcriptomic analysis of human neocortical development
Authors: Polioudakis Damon , Torre-Ubieta Luis de la , Langerman Justin , Elkins Andrew G. , Stein Jason L. , Vuong Celine K. , Opland Carli K. , Lu Daning , Connell William , Ruzzo Elizabeth K. , Lowe Jennifer K. , Hadzic Tarik , Hinz Flora I. , Sabri Shan , Lowry William E. , Plath Kathrin , Geschwind Daniel H.
Published: August 2018

Defining the number, proportion, or lineage of distinct cell types in the developing human brain is an important goal of modern brain research. We defined single cell transcriptomic profiles for 40,000 cells at mid-gestation to identify cell types in the developing human neocortex. We define expression profiles corresponding to all known major cell types at this developmental period and identify multiple transcription factors and co-factors expressed in specific cell types, providing an unprecedented resource for understanding human neocortical development including the first single-cell characterization of human subplate neurons. We characterize major developmental trajectories during early neurogenesis, showing that cell type differentiation occurs on a continuum that involves transitions that tie cell cycle progression with early cell fate decisions. We use these data to deconvolute regulatory networks and map neuropsychiatric disease genes to specific cell types, implicating dysregulation of specific cell types, as the mechanistic underpinnings of several neurodevelopmental disorders. Together these results provide an extensive catalog of cell types in human neocortex and extend our understanding of early cortical development, human brain evolution and the cellular basis of neuropsychiatric disease.

One Sentence Summary

Comprehensive single cell transcriptomes in developing human cortex inform models of cell diversity, differentiation and disease risk.
Frontal and occipito-temporal Theta activity as marker of error monitoring in Human-Avatar joint performance
Authors: Moreau Q. , Candidi M. , Era V. , Tieri G. , Aglioti S.M.
Published: August 2018

Discrepancies between sensory predictions and action outcome are at the base of error coding. However, these phenomena have mainly been studied focusing on individual performance. Here, we explored prediction errors during a human-avatar motor interaction and focused on both the classical frontal error-related brain responses and the activity of the action observation network. Our motor interaction paradigm required healthy individuals to synchronize their reach-to-grasp movements with those of a virtual partner in conditions that did (Interactive) or did not require (Cued) movement prediction and adaptation to the partner’s actions. Crucially, in 30% of the trials the virtual partner suddenly and unpredictably changed its movement trajectory thereby violating the human participant’s expectation. These changes elicited error-related neuromarkers (ERN/Pe - Theta/Alpha modulations) over fronto-central electrodes mainly during the Interactive condition. Source localization and connectivity analyses showed that the frontal Theta activity induced by violations of the expected interactive movements was in phase with occipito-temporal Theta activity. These results expand current knowledge about the neural correlates of on-line motor interactions linking the frontal error-monitoring system to visual, body motion-related, responses.
Competition within species determines the value of a mutualism between species
Authors: Sun Syuan-Jyun , Horrocks Nicholas P.C. , Kilner Rebecca M.
Published: August 2018

Social interactions within species, and mutualisms between species are both well characterised, but their influence on each other is poorly understood. We determined how interactions among burying beetlesNicrophorus vespilloidesinfluence the value of their interactions with the mitePoecilochirus carabi.Beetles transport these mites to carrion, upon which both species breed. We show that mites help beetles win intraspecific contests for this scarce resource: mites raise beetle body temperature, which enhances beetle competitive prowess. However, mites confer this benefit only upon smaller beetles, which are otherwise doomed by their size to lose contests for carrion. Larger beetles need no assistance to win a carcass and lose reproductive success when breeding alongside mites. We conclude that social interactions within species explain whether interactions with another species are mutualistic or parasitic.

One Sentence Summary

Social interactions within species can explain whether interactions with a second species are mutualistic or parasitic.
Extrinsic and Intrinsic Dynamics in Movement Intermittency
Authors: Susilaradeya Damar , Xu Wei , Hall Thomas M , Galán Ferran , Alter Kai , Jackson Andrew
Published: August 2018

What determines how we move in the world? Motor neuroscience often focusses either on intrinsic rhythmical properties of motor circuits or extrinsic sensorimotor feedback loops. Here we show that the interplay of both intrinsic and extrinsic dynamics is required to explain the intermittency observed in continuous tracking movements. Using spatiotemporal perturbations in humans, we demonstrate that apparently discrete submovements made 2-3 times per second reflect constructive interference between motor errors and continuous feedback corrections that are filtered by intrinsic circuitry in the motor system. Local field potentials in monkey motor cortex revealed characteristic signatures of a Kalman filter giving rise to both low-frequency cortical cycles during movement, and delta oscillations during sleep. We interpret these results within the framework of optimal feedback control, and suggest that the intrinsic rhythmicity of motor cortical networks reflects an internal model of external dynamics which is used for state estimation during feedback-guided movement.
Cdc42 negatively regulates endocytosis during apical plasma membrane maintenance and development in mouse tubular organs in vivo
Authors: Shitara Akiko , Malec Lenka , Ebrahim Seham , Chen Desu , Bleck Christopher , Hoffman Matthew P. , Weigert Roberto
Published: August 2018

Lumen establishment and maintenance are fundamental for tubular organs physiological functions. Most of the studies investigating the mechanisms regulating this process have been carried out in cell cultures or in smaller organisms, whereas little has been done in mammalian model systems in vivo. Here we used the salivary glands of live mice to examine the role of the small GTPase Cdc42 in the regulation of the homeostasis of the intercellular canaliculi, a specialized apical domain of the acinar cells, where protein and fluid secretion occur. Depletion of Cdc42 in adult mice induced a significant expansion of the apical canaliculi, whereas depletion at late embryonic stages resulted in a complete inhibition of their post-natal formation. In addition, intravital subcellular microscopy revealed that reduced levels of Cdc42 affected membrane trafficking from and towards the plasma membrane, highlighting a novel role for Cdc42 in membrane remodeling through the negative regulation of selected endocytic pathways.
Association of SRB1, ITGB2 gene polymorphisms with coronary heart disease in Chinese Han population
Authors: Sun Yuan , Long-Wang Tian , Zeng Yong , Gong Feng-Ying , Zhu Hui-Juan , Pan Hui , Wang Ying , Wang Jia-Li
Published: August 2018

Background

Previous studies in mice and humans have implicated the lipoprotein receptor SRB1 in association with atherosclerosis and lipid levels. In our previous proteomics research, the expression of ITGB2 has differences between epicardial and subcutaneous adipose tissue. However, the association between the reported variants and risk of coronary heart disease (CHD) was not confirmed.

Methods

We conducted a case–control study consisted of 496 CHD patients and 367 controls. The two groups are adjusted for age, sex, body mass index, diabetes status and the proportion of dyslipidemia. The genotypes and allele frequency of variants rs838880,rs5888,rs5889 in SRB1 and rs235326,rs2070947,rs2070946 in ITGB2 were determined using Sequenom Mass-ARRAY technology.

Results

The genotypes frequencies of all the six SNPs were consistent with Hardy-Weinberg Equilibrium test. For gene SRB1 rs838880, there was a significant difference in the alleles frequency(p=0.017), genotype frequency(p=0.0028), recessive model (p=0.000672) between CHD group and control group. For gene ITGB2 rs2070947, there was a significant difference in the recessive model (p=0.03). By comparing the clinical and serum metabolic indexes of SNP sites by genotype we find that among three genotypes of SRB1 rs5888,there were significant difference in the level of dyslipidemia history and serum LPA, among three genotypes of ITGB2 rs235236,there were significant difference in the levels of serum HDL,APOA1 and hypertension history, among three genotypes of ITGB2 rs2070947,there were significant difference in the level of serum APOA1,hsCRP.

Conclusions

Our findings indicated that SNP rs838880 of gene SRB1 and rs2070947 of gene ITGB2 are associated with the risk of CHD in Chinese han population.
Temporal dependence of shifts in mu opioid receptor mobility at the cell surface after agonist binding observed by single-particle tracking
Authors: Metz Marissa J. , Pennock Reagan L. , Krapf Diego , Hentges Shane T.
Published: August 2018

Agonist binding to the mu opioid receptor (MOR) results in conformational changes that allow recruitment of G-proteins, activation of downstream effectors and eventual desensitization and internalization, all of which could affect receptor mobility. The present study employed single particle tracking (SPT) of quantum dot labeled FLAG-tagged MORs to examine shifts in MOR mobility after agonist binding. FLAG-MORs on the plasma membrane were in both mobile and immobile states under basal conditions. Activation of FLAG-MORs with DAMGO caused an acute increase in the fraction of mobile MORs, and free portions of mobile tracks were partially dependent on interactions with G-proteins. In contrast, 10-minute exposure to DAMGO or morphine increased the fraction of immobile FLAG-MORs. While the decrease in mobility with prolonged DAMGO exposure corresponded to an increase in colocalization with clathrin, the increase in colocalization was present in both mobile and immobile FLAG-MORs. Thus, no single mobility state of the receptor accounted for colocalization with clathrin. These findings demonstrate that SPT can be used to track agonist-dependent changes in MOR mobility over time, but that the mobility states observed likely arise from a diverse set of interactions and will be most informative when examined in concert with particular downstream effectors.
Elimination of Vesicular Zinc Alters the Behavioural and Neuroanatomical Effects of Social Defeat Stress in Mice
Authors: McAllister Brendan B. , Wright David K. , Wortman Ryan C. , Shultz Sandy R. , Dyck Richard H.
Published: August 2018

Chronic stress can have deleterious effects on mental health, increasing the risk of developing depression or anxiety. But not all individuals are equally affected by stress; some are susceptible while others are more resilient. Understanding the mechanisms that lead to these differing outcomes has been a focus of considerable research. One unexplored mechanism is vesicular zinc – zinc that is released by neurons as a neuromodulator. We examined how chronic stress, induced by repeated social defeat, affects mice that lack vesicular zinc due to genetic deletion of zinc transporter 3 (ZnT3). These mice, unlike wild type mice, did not become socially avoidant of a novel conspecific, suggesting resilience to stress. However, they showed enhanced sensitivity to the potentiating effect of stress on cued fear memory. Thus, the contribution of vesicular zinc to stress susceptibility is not straightforward. Stress also increased anxiety-like behaviour but produced no deficits in a spatial Y-maze test. We found no evidence that microglial activation or hippocampal neurogenesis accounted for the differences in behavioural outcome. Volumetric analysis revealed that ZnT3 KO mice have larger corpus callosum and parietal cortex volumes, and that corpus callosum volume was decreased by stress in ZnT3 KO, but not wild type, mice.
Activation of polarized cell growth by inhibition of cell polarity
Authors: Geymonat Marco , Chessel Anatole , Dodgson James , Punter Hannah , Horns Felix , Nagy Attila Csikász , Carazo Salas Rafael Edgardo
Published: August 2018

A key feature of cells is the capacity to activate new functional polarized domains contemporaneously to pre-existing ones. How cells accomplish this is not clear. Here, we show that in fission yeast inhibition of cell polarity at pre-existing domains of polarized cell growth is required to activate new growth. This inhibition is mediated by the ERM-related polarity factor Tea3, which antagonizes the activation of the Rho-GTPase Cdc42 by its co-factor Scd2. We demonstrate that Tea3 acts in a phosphorylation-dependent manner controlled by the PAK kinase Shk1 and that, like Scd2, Tea3 is direct substrate of Shk1. Importantly, we show that Tea3 and Scd2 compete for their binding to Shk1, indicating that their biochemical competition for Shk1 underpins their antagonistic roles in controlling polarity. Thus, by preventing pre-existing growth domains from becoming overpowering, Tea3 allows cells to redistribute their polarity-activating machinery to prospective sites and control their timing of activation.
Oncogenic activation of Nrf2 by specific knockout of Nrf1α that acts as a dominant tumor repressor
Authors: Qiu Lu , Wang Meng , Hu Shaofan , Ru Xufang , Ren Yonggang , Yu Siwang , Zhang Yiguo
Published: August 2018

Liver-specific knockout of Nrf1 in mice leads to non-alcoholic steatohepatitis with dyslipidemia, and its deterioration results in spontaneous hepatoma, but the underlying mechanism remains elusive. A similar pathological model is herein reconstructed by using human Nrf1α-specific knockout cell lines. We demonstrated that a marked increase of the inflammation marker COX2 in Nrf1α−/− cells. Loss of Nrf1α leads to hyperactivation of Nrf2, which results from substantial decreases in both Keap1 and PTEN in Nrf1α−/− cells. Further investigation of xenograft mice showed that malignant growth of Nrf1α−/−-derived tumor is almost abolished by silencing Nrf2, while Nrf1α+/+-tumor is markedly repressed by inactive Nrf2−/−ΔTA, but unaffected by a priori constitutive activator of caNrf2ΔN. Mechanistic studies unraveled there exist opposing and unifying inter-regulatory cross-talks between Nrf1 and Nrf2. Collectively, Nrf1α manifests a dominant tumor-suppressive effect by confining Nrf2 oncogenicity, while Nrf2 can directly activate the transcriptional expression of Nrf1 to form a negative feedback loop.

HIGHLIGHTS

Opposing and unifying inter-regulatory cross-talks between Nrf1α and Nrf2

Malignant growth of Nrf1α−/−-derived tumor is prevented by silencing Nrf2

Hyper-activation of Nrf2 by Nrf1α−/− results from decreased Keap1 and PTEN

Nrf1α+/+-tumor is repressed by Nrf2−/−ΔTA, but unaltered by its active caNrf2ΔN
Multiple isotopic models using various kinetic fractionation coefficients to estimateδ18O of leaf water
Authors: Zhang Yonge , Yu Xinxiao , Chen Lihua , Jia Guodong
Published: August 2018

Investigation ofδ18O of leaf water may improve our understanding of the evapotranspiration partitioning and material exchange between the inside and outside of leaves. In this study,δ18O of bulk leaf water (δL,b) was estimated by both isotopic–steady–state (ISS) and non–steady–state (NSS) assumptions considering the Péclet effect. Specifically, we carefully modified kinetic fractionation coefficients (αk). The results showed that the Péclet effect is required to predictδL,b. On the diel time scale, both NSS assumption + Péclet effect (NSS + P) and ISS assumption + Péclet effect (ISS + P) using modifiedαk(αk–modified) forδL,bshowed a good agreement with observedδL,b(p> 0.05). When using previously proposedαk, however, both NSS + P and ISS + P were not reliable estimators ofδL,b(p< 0.05). On a longer time scale (days), estimates of daily meanδL,bfrom ISS + P outperformed the estimates from NSS + P when using the sameαkvalues. Also, the employment ofαk–modifiedimproved model performance in predicting daily meanδL,bcompared to the use of previously proposedαk. Clearly, special care must be taken concerningαkwhen using isotopic models to estimateδL,b.

Highlight

For hourly and daily mean data sets, the employment of modified kinetic fractionation coefficients significantly improved model performance forδ18O of bulk leaf water.
Arterio-Venous Remodeling in the Zebrafish Trunk is Controlled by Genetic Programming and Flow-Mediated Fine-Tuning
Authors: Geudens Ilse , Coxam Baptiste , Alt Silvanus , Gebala Véronique , Vion Anne-Clémence , Rosa Andre , Gerhardt Holger
Published: August 2018

How developing vascular networks acquire the right balance of arteries, veins and lymphatics to efficiently supply and drain tissues is poorly understood [1, 2]. In zebrafish embryos, the robust and regular 50:50 global balance of intersegmental veins and arteries that form along the trunk [3], prompts the intriguing question how the organism keeps “count”. Previous studies suggest that the ultimate fate of an intersegmental vessel (ISV) is determined by the identity of the approaching secondary sprout emerging from the posterior cardinal vein (PCV) [1, 4-7]. Here, using high time-resolution imaging, advanced cell tracking and computational analysis, we show that the formation of a balanced trunk vasculature involves an early heterogeneity in endothelial cell (EC) behavior in the seemingly identical primary ISVs and an adaptive flow-mediated mechanism that fine-tunes the balance of arteries and veins along the trunk. Detailed examination of the trunk vasculature dynamics throughout development reveals the frequent formation of three-way vascular connections between primary ISVs, the dorsal aorta (DA) and the PCV. Differential resolution of these connections into arteries or veins is mediated by polarized cell movement of the ECs within the ISV. Quantitative analysis of the cellular organization, polarity and directional movement of ECs in primary ISVs identifies an early differential behavior between future arteries and veins that is largely specified in the ECs of the individual ISVs, is dependent on Dll4/Notch, and occurs even in the absence of secondary sprouting. Notch signaling is involved in a local patterning mechanism normally favoring the formation of alternating arteries and veins. The global artery-vein balance is however maintained through a flow-dependent mechanism that can overwrite the local patterning. We propose that this dual mechanism driving arterio-venous identity during developmental angiogenesis in the zebrafish trunk provides the adaptability required to establish a balanced network of arteries, veins and lymphatic vessels.
Effect of methylene blue on the formation of oxidized phospholipid vesicles
Authors: Fabre J-F. , Cerny M. , Cassen A. , Mouloungui Z.
Published: August 2018

Soybean phosphatidylcholine, which is rich in linoleic acid, was oxidized with singlet oxygen through photosensitization with methylene blue. This compound facilitates the oxidation of phospholipids relative to the reaction with free unsaturated fatty acids. A response surface methodology was used to control oxidation, with methylene blue concentration and the amount of available air as independent variables. The conjugated diene-to triene ratio was then monitored. Hydroperoxide yield dependent principally on the amount of air, whereas photosensitizer concentration strongly influenced the size and zeta potential of vesicles formed by the sonication of oxidized phospholipids in water. Methylene blue plays an important role in the surface charge expression and ion permeability of these vesicles.
Bond orders for intermolecular interactions in crystals: charge transfer, ionicity and the effect on intramolecular bonds
Authors: Alhameedi Khidhir , Karton Amir , Jayatilaka Dylan , Thomas Sajesh P.
Published: August 2018

The question of whether intermolecular interactions in crystals originate from localized atom...atom interactions or as a result of holistic molecule...molecule close packing is a matter of continuing debate. In this context, the newly introduced Roby–Gould bond indices are reported for intermolecular `σ-hole' interactions, such as halogen bonding and chalcogen bonding, and compared with those for hydrogen bonds. A series of 97 crystal systems exhibiting these interaction motifs obtained from the Cambridge Structural Database (CSD) has been analysed. In contrast with conventional bond-order estimations, the new method separately estimates the ionic and covalent bond indices for atom...atom and molecule...molecule bond orders, which shed light on the nature of these interactions. A consistent trend in charge transfer from halogen/chalcogen bond-acceptor to bond-donor groups has been found in these intermolecular interaction regions via Hirshfeld atomic partitioning of the electron populations. These results, along with the `conservation of bond orders' tested in the interaction regions, establish the significant role of localized atom...atom interactions in the formation of these intermolecular binding motifs.
Theoretical insight into the disordered structure of (Z)-2-[(E)-(4-methoxybenzylidene)hydrazinylidene]-1,2-diphenylethanone: the role of noncovalent interactions
Authors: Tan Xue-Jie , Wang Di , Lei Xu-Gang , Chen Jun-Peng
Published: August 2018

A global glide disorder has been discovered during an X-ray investigation of the crystal structure of (Z)-2-[(E)-(4-methoxybenzylidene)hydrazinylidene]-1,2-diphenylethanone (MHDE, C22H18N2O2) at room temperature. In another crystal, however, such disorder disappears (still at room temperature). Even though the disorder may be partly due to the poor quality of the harvested crystal, the structure can shed light on the nature of disorder. With the help of quantum chemical calculations, it is found that the global disorder seems to be connected with the need for stabilization of the somewhat rigid but mobile and unstable molecular structure. The most relevant feature driving the packing of the disordered structure concerns the slight perturbations (such as glide) of two or more disorder components (fractional occupancies) distributed throughout the crystal.
TssA from Burkholderia cenocepacia: expression, purification, crystallization and crystallographic analysis
Authors: Owen Hayley J. , Sun Ruyue , Ahmad Asma , Sedelnikova Svetlana E. , Baker Patrick J. , Thomas Mark S. , Rice David W.
Published: August 2018

TssA is a core component of the type VI secretion system, and phylogenetic analysis of TssA subunits from different species has suggested that these proteins fall into three distinct clades. Whilst representatives of two clades, TssA1 and TssA2, have been the subjects of investigation, no members of the third clade (TssA3) have been studied. Constructs of TssA from Burkholderia cenocepacia, a representative of clade 3, were expressed, purified and subjected to crystallization trials. Data were collected from crystals of constructs of the N-terminal and C-terminal domains. Analysis of the data from the crystals of these constructs and preliminary structure determination indicates that the C-terminal domain forms an assembly of 32 subunits in D
16 symmetry, whereas the N-terminal domain is not involved in subunit assocation.
Analysing the barriers of lean in Indian coal mining industry using integrated ISM-MICMAC and SEM
Authors: Khaba Sorokhaibam , Bhar Chandan
Published: August 2018

Purpose

The purpose of this paper is to develop and validate a model for key barriers to lean implementation in the Indian coal mining industry.

Design/methodology/approach

Interpretive structural modeling (ISM) has been used to develop a proper hierarchy and contextual relationship of key barriers to lean implementation in the Indian coal mining industry through literature review and expert opinion which is followed by the classification of barriers using Matrice d’ Impacts Croisés-Multiplication Appliquée á un Classement (MICMAC) and questionnaire-based survey to validate the ISM model using structural equation modeling (SEM).

Findings

In this study, 14 key barriers to lean implementation in the Indian coal mining industry have been identified, modeled and analyzed. The lack of top management commitment, financial constraints and lack of inter-departments co-ordination are found to be the most important barriers to lean implementation in the mining industry. The ISM-based model is validated using the SEM.

Research limitations/implications

The analysis of data represents that relatively more participants were from the mines located in eastern India and the maximum participants were managers and executives holding different levels (lower, middle or upper), although key participants in different mines were encouraged to distribute the survey to other employees also.

Practical implications

This model on lean barriers would help the decision makers, researchers and practitioners to anticipate potential barriers to lean implementation and support the existing academic research on lean. Accordingly, the focus on the lean barriers can be prioritized for the better utilization of the available resources for eliminating or minimizing the barriers.

Originality/value

This paper is an original contribution of analysis of the lean barriers in Indian mining industry using the integrated ISM–MICMAC and SEM approach.
Assessing congestion in emergency obstetric care in public hospitals in Tamil Nadu
Authors: Rajasulochana Subramania Raju , Matranga Domenica
Published: August 2018

Purpose

The purpose of this paper is to assess congestion as the simultaneous occurrence of desirable health output (e.g. maternal admissions) along with undesirable output (e.g. still births (SB)), in emergency obstetric care settings of public hospitals in Tamil Nadu.

Design/methodology/approach

The study is based on a cross-sectional data set of 97 public hospitals collected by the statistical cell of Tamil Nadu Health Systems Project for the year 2013–2014. The study uses three inputs – beds, doctors and nurses; three desirable outputs – maternal admissions, neonatal admission and live births; and four undesirable outputs – SB, intra-uterine deaths, neonatal deaths and maternal deaths. Congestion analysis, a variant of the data envelopment analysis (DEA) method and slack analysis, has been applied to detect an excessive use of some inputs or a shortfall in some outputs across these hospitals. Furthermore, the association between congestion and some contextual factors has been examined.

Findings

On an average, the hospitals in our sample can increase the total amount of outputs by 62.8 percent by improving overall efficiency, and about 34.2 percent of this inefficiency can be attributed to congestion. Analysis of sub-samples showed that government hospitals at the taluk level have higher congestion than district headquarter hospitals. Congestion seems to decrease with greater hospital volume up to a limit; beyond that, it increases in obstetric care settings.

Originality/value

Hospital-based efficiency studies in the Indian context, so far, have estimated relative efficiency among hospitals using the classical DEA method, but ignoring adverse health outcomes. Congestion analysis, an advance in the DEA method, considers how much the desirable outputs can be increased as also how much undesirable outputs affect efficiency.
A framework for assessing quantity surveyors’ competence
Authors: Dada Joshua Oluwasuji , Jagboro Godwin Onajite
Published: August 2018

Purpose

The purpose of this paper is to develop a conceptual framework for assessing quantity surveyors’ competence level.

Design/methodology/approach

Delphi survey research approach was adopted for the study. This involved a survey of panel of experts, constituted among registered quantity surveyors in Nigeria, and obtaining from them a consensus opinion on the issues relating to the assessment of quantity surveyors’ competence. In total, 27 out of the shortlisted 38 member panel provided valid results in the two rounds of Delphi survey conducted. A conceptual framework linking educational training, professional capability and professional development is developed.

Findings

The findings establish the ratings of the identified three competence criteria. On a scale of 0–100 percent rating, educational training was scored 34.04 percent, professional capability 45.22 percent and professional development 20.74 percent.

Originality/value

The proposed framework provide a conceptual approach in assessing quantity surveyor overall competence. Specifically, it demonstrates the significance of the identified three competence criteria groupings in the training, practice and development of quantity surveying profession. It could therefore serves as foundation of on how quantity surveyors are trained, developed and evaluated.
Does outsourcing always work? A critical evaluation for project business success
Authors: Sandhu Maqsood Ahmad , Shamsuzzoha Ahm , Helo Petri
Published: August 2018

Purpose

The purpose of this paper is to deal with the importance and obstacles of outsourcing strategy in project business in terms of product development perspectives. This strategy is intrinsically analyzed and evaluated with respect to the strategic business environments.

Design/methodology/approach

The objective of this research is to analyze the advantages and limitations of the outsourcing that have been identified in prior studies. This research has attempted to investigate the performance implications of outsourcing strategies in terms of theoretical considerations and implementation perspectives.

Findings

In this study, the authors have presented a general overview of outsourcing strategies in terms of both light and dark sides of this approach. Various driving forces of outsourcing strategy along with critical success factors are articulated within project to product development perspectives.

Research limitations/implications

Future research could be continued to measure various performance variables such as productivity, sales, revenues, career opportunities, manifest in power struggles, change jobs, change organizational cultures, etc. in multiple case companies, which affect with the success or failure of outsourcing arrangements.

Practical implications

The term outsourcing is nowadays a widely known business strategy, where manufacturing firms share partly or fully of their production process with outside organizations or suppliers. The research approach as articulated within this paper would be beneficial for project business organizations and specially the product designers and project managers for planning and developing their strategic business potentials with respect to outsourcing and in-sourcing decisions.

Originality/value

In this paper a high-level decision-making model for outsourcing and a cause and effect type framework are demonstrated with a view to ease the decision-making process for the organizations managers.