bluuebunny/crossref_metadata_2025 huggingface dataset:
Spacer sequences separating transcription factor binding motifs set enhancer quality and strength
Authors: Guéroult-Bellone Marion , Nitta Kazuhiro R. , Kari Willi , Jacox Edwin , Beulé Dauzat Rémy , Vincentelli Renaud , Diarra Carine , Rothbächer Ute , Dantec Christelle , Cambillau Christian , Piette Jacques , Lemaire Patrick
Published: January 2017

Only a minority of the many genomic clusters of transcription factor binding motifs (TFBM) act as transcriptional enhancers. To identify determinants of enhancer activity, we randomized the spacer sequences separating the ETS and GATA sites of the early neural enhancer of the tunicateCiona intestinalis Otxgene. We show that spacer sequence randomization affects the level of activity of the enhancer, in part through distal effects on the affinity of the transcription factors for their binding sites. A possible mechanism is suggested by the observation that the shape of the DNA helix within the TFBM can be affected by mutation of flanking bases that modulate transcription factor affinity. Strikingly, dormant genomic clusters of ETS and GATA sites are awakened by most instances of spacer randomization, suggesting that the sequence of naturally-occurring spacers ensures the dormancy of a majority of the large reservoir of TFBM clusters present in a metazoan genome.
ER-positive breast cancer cells are poised for RET-mediated endocrine resistance
Authors: Horibata Sachi , Rice Edward J. , Zheng Hui , Anguish Lynne J. , Coonrod Scott A. , Danko Charles G.
Published: January 2017

The RET tyrosine kinase signaling pathway is involved in the development of endocrine resistant ER+ breast cancer. However, the expression of the RET receptor itself has not been directly linked to clinical cases of resistance, suggesting that additional factors are involved. We show that both ER+ endocrine resistant and sensitive breast cancers have functional RET tyrosine kinase signaling pathway, but that endocrine sensitive breast cancer cells lack RET ligands that are necessary to drive endocrine resistance. Transcription of one RET ligand, GDNF, is necessary and sufficient to confer resistance in the ER+ MCF-7 cell line. In patients, RET ligand expression predicts responsiveness to endocrine therapies and correlates with survival. Collectively, our findings show that ER+ tumor cells are “poised” for RET mediated endocrine resistance, expressing all components of the RET signaling pathway, but endocrine sensitive cells lack high expression of RET ligands that are necessary to initiate the resistance phenotype.
Structural landscape of base pairs containing post-transcriptional modifications in RNA
Authors: S. P. Preethi , Sharma Purshotam , Mitra Abhijit
Published: January 2017

Base pairs involving post-transcriptionally modified nucleobases are believed to play important roles in a wide variety of functional RNAs. Here we present our attempts towards understanding the structural and functional role of naturally occurring modified base pairs by analyzing their distribution in different RNA classes, with the help of crystal structure and sequence database analyses. In addition, we quantify the variation in geometrical features of modified base pairs within RNA structures, and characterize their optimum geometries and binding energies using advanced quantum chemical methods. Further comparison of modified base pairs with their unmodified counterparts illustrates the effect of steric and electronic structure alterations due to base modifications. Analysis of specific structural contexts of modified base pairs in RNA crystal structures revealed several interesting scenarios, including those at the tRNA:rRNA interface, antibiotic-binding site and the three-way junctions within tRNA, which when analyzed in context of available experimental data, allowed us to correlate the occurrence and strength of modified base pairs with the specific functional roles they play in context of RNA macromolecules.
Potassium channels contribute to activity-dependent scaling of dendritic inhibition
Authors: Chang Jeremy T. , Higley Michael J.
Published: January 2017

GABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.

Significance Statement

GABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.
A Comparison of mRNA Sequencing with Random Primed and 3’-Directed Libraries
Authors: Xiong Yuguang , Soumillon Magali , Wu Jie , Hansen Jens , Hu Bin , van Hasselt Johan G.C. , Jayaraman Gomathi , Lim Ryan , Bouhaddou Mehdi , Ornelas Loren , Bochicchio Jim , Lenaeus Lindsay , Stocksdale Jennifer , Shim Jaehee , Gomez Emilda , Sareen Dhruv , Svendsen Clive , Thompson Leslie M. , Mahajan Milind , Iyengar Ravi , Sobie Eric A. , Azeloglu Evren U. , Birtwistle Marc R.
Published: January 2017

Deep mRNA sequencing (mRNAseq) is the state-of-the-art for whole transcriptome measurements. A key step is creating a library of cDNA sequencing fragments from RNA. This is generally done by random priming, creating multiple sequencing fragments along the length of each transcript. A 3’ end-focused library approach cannot detect differential splicing, but has potentially higher throughput at lower cost (~10-fold lower), along with the ability to improve quantification by using transcript molecule counting with unique molecular identifiers (UMI) to correct for PCR bias. Here, we compare implementation of such a 3’-digital gene expression (3’-DGE) approach with “conventional” random primed mRNAseq, which has not yet been done. We find that while conventional mRNAseq detects ~15% more genes, the resulting lists of differentially expressed genes and therefore biological conclusions and gene signatures are highly concordant between the two techniques. We also find good quantitative agreement on the level of individual genes between the two techniques in terms of both read counts and fold change between two conditions. We conclude that for high-throughput applications, the potential cost savings associated with the 3’-DGE approach are a very reasonable tradeoff for modest reduction in sensitivity and inability to observe alternative splicing, and should enable much larger scale studies focused on not only differential expression analysis, but also quantitative transcriptome profiling. The computational scripts and programs, along with experimental standard operating procedures used in our pipeline presented here, are freely available on our website (www.dtoxs.org).
The demographic and adaptive history of the African green monkey
Authors: Pfeifer Susanne P.
Published: January 2017

Relatively little is known about the evolutionary history of the African green monkey (genusChlorocebus) due to the lack of sampled polymorphism data from wild populations. Yet, this characterization of genetic diversity is not only critical for a better understanding of their own history, but also for human biomedical research given that they are one of the most widely used primate models. Here, I analyze the demographic and selective history of the African green monkey, utilizing one of the most comprehensive catalogs of wild genetic diversity to date, consisting of 1,795,643 autosomal single nucleotide polymorphisms in 25 individuals, representing all five major populations:C. a. aethiops,C. a. cynosurus,C. a. pygerythrus,C. a. sabaeus, andC. a tantalus. Assuming a mutation rate of 5.9 × 10−9per base pair per generation and a generation time of 8.5 years, divergence time estimates range from 523-621kya for the basal split ofC. a. aethiopsfrom the other four populations. Importantly, the resulting tree characterizing the relationship and split-times between these populations differs significantly from that presented in the original genome paper, owing to their neglect of within-population variation when calculating between population-divergence. In addition, I find that the demographic history of all five populations is well explained by a model of population fragmentation and isolation, rather than novel colonization events. Finally, utilizing these demographic models as a null, I investigate the selective history of the populations, identifying candidate regions potentially related to adaptation in response to pathogen exposure.
Distinguishing Mechanisms Underlying EMT Tristability
Authors: Jia Dongya , Jolly Mohit Kumar , Tripathi Satyendra C. , Hollander Petra Den , Huang Bin , Lu Mingyang , Celiktas Muge , Ramirez-Peña Esmeralda , Ben-Jacob Eshel , Onuchic José N. , Hanash Samir M. , Mani Sendurai A. , Levine Herbert
Published: January 2017

Background:

The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models – ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done.

Results:

Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E→E/M→M, the different responses of SNAIL and ZEB1 to exogenous TGF-β and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2.

Conclusions:

These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes.
Effect of a selective SGLT2 inhibitor, luseogliflozin, on circadian rhythm of sympathetic nervous function and locomotor activities in metabolic syndrome rats
Authors: Rahman Asadur , Fujisawa Yoshihide , Nakano Daisuke , Hitomi Hirofumi , Nishiyama Akira
Published: January 2017

Metabolic syndrome is often associated with disruption of circadian rhythm of systemic haemodynamics and cardiovascular disease. Experiments were conducted to investigate the effects of luseogliflozin, a selective SGLT2 inhibitor, on circadian rhythm of sympathetic nervous function and locomotor activity (LA) in metabolic syndrome rats. The difference in the low frequency component of systolic blood pressure between the dark and light period significantly increased in the luseogliflozin‐treated SHRcp. LA also increased in the dark period compared with the light period following luseogliflozin treatment. These data suggest that circadian rhythm of sympathetic nervous function and LA is improved by luseogliflozin in metabolic syndrome rats, which may contribute to SGLT2 inhibitor‐induced improvement of cardiovascular outcomes.
Soil microbial communities are shaped by vegetation type and park age in cities under cold climate
Authors: Hui Nan , Jumpponen Ari , Francini Gaia , Kotze D. Johan , Liu Xinxin , Romantschuk Martin , Strömmer Rauni , Setälä Heikki
Published: January 2017

Soil microbes play a key role in controlling ecosystem functions and providing ecosystem services. Yet, microbial communities in urban green space soils remain poorly characterized. Here we compared soil microbial communities in 41 urban parks of (i) divergent plant functional types (evergreen trees, deciduous trees and lawn) and (ii) different ages (constructed 10, ∼50 and >100 years ago). These microbial communities were also compared to those in 5 control forests in southern Finland. Our results indicate that, despite frequent disturbances in urban parks, urban soil microbes still followed the classic patterns typical of plant‐microbe associations in natural environments: both bacterial and fungal communities in urban parks responded to plant functional groups, but fungi were under tighter control of plants than bacteria. We show that park age shaped the composition of microbial communities, possibly because vegetation in old parks have had a longer time to modify soil properties and microbial communities than in young parks. Furthermore, control forests harboured distinct but less diverse soil microbial communities than urban parks that are under continuous anthropogenic disturbance. Our results highlight the importance of maintaining a diverse portfolio of urban green spaces and plant communities therein to facilitate complex microbial communities and functions in urban systems.
Biogeochemical spatio‐temporal transformation of copper in Aspergillus niger colonies grown on malachite with different inorganic nitrogen sources
Authors: Fomina Marina , Bowen Andrew D. , Charnock John M. , Podgorsky Valentin S. , Gadd Geoffrey M.
Published: January 2017

This work elucidates spatio‐temporal aspects of the biogeochemical transformation of copper mobilized from malachite (Cu2(CO3)(OH)2) and bioaccumulated within Aspergillus niger colonies when grown on different inorganic nitrogen sources. It was shown that the use of either ammonium or nitrate determined how copper was distributed within the colony and its microenvironment and the copper oxidation state and succession of copper coordinating ligands within the biomass. Nitrate‐grown colonies yielded ∼1.7× more biomass, bioaccumulated ∼7× less copper, excreted ∼1.9× more oxalate and produced ∼1.75× less water‐soluble copper in the medium in contrast to ammonium‐grown colonies. Microfocus X‐ray absorption spectroscopy revealed that as the mycelium matured, bioaccumulated copper was transformed from less stable and more toxic Cu(I) into less toxic Cu(II) which was coordinated predominantly by phosphate/malate ligands. With time, a shift to oxalate coordination of bioaccumulated copper occurred in the central older region of ammonium‐grown colonies.
Symbiotic bacteria associated with a bobtail squid reproductive system are detectable in the environment, and stable in the host and developing eggs
Authors: Kerwin Allison H. , Nyholm Spencer V.
Published: January 2017

Female Hawaiian bobtail squid, Euprymna scolopes, have an accessory nidamental gland (ANG) housing a bacterial consortium that is hypothesized to be environmentally transmitted and to function in the protection of eggs from fouling and infection. The composition, stability, and variability of the ANG and egg jelly coat (JC) communities were characterized and compared to the bacterial community composition of the surrounding environment using Illumina sequencing and transmission electron microscopy. The ANG bacterial community was conserved throughout hosts collected from the wild and was not affected by maintaining animals in the laboratory. The core symbiotic community was composed of Alphaproteobacteria and Opitutae (a class of Verrucomicrobia). Operational taxonomic units representing 94.5% of the average ANG abundance were found in either the seawater or sediment, which is consistent with the hypothesis of environmental transmission between generations. The bacterial composition of the JC was stable during development and mirrored that of the ANG. Bacterial communities from individual egg clutches also grouped with the ANG of the female that produced them. Collectively, these data suggest a conserved role of the ANG/JC community in host reproduction. Future directions will focus on determining the function of this symbiotic community, and how it may change during ANG development.
Health Risk Factors Associated with Lifetime Abstinence from Alcohol in the 1979 National Longitudinal Survey of Youth Cohort
Authors: Kerr William C. , Lui Camillia K. , Williams Edwina , Ye Yu , Greenfield Thomas K. , Lown E. Anne
Published: January 2017

Background

The choice and definition of a comparison group in alcohol‐related health studies remains a prominent issue in alcohol epidemiology due to potential biases in the risk estimates. The most commonly used comparison group has been current abstainers; however, this includes former drinkers who may have quit drinking due to health problems. Lifetime abstention could be the best option, but measurement issues, selection biases due to health and other risk factors, and small numbers in populations are important concerns. This study examines characteristics of lifetime abstention and occasional drinking that are relevant for alcohol‐related health studies.

Methods

This study used data from the National Longitudinal Survey of Youth 1979 cohort of 14 to 21 year olds followed through 2012 (n = 7,515). Definitions of abstinence and occasional drinking were constructed based on multiple measurements. Descriptive analyses were used to compare the definitions, and in further analysis, lifetime abstainers (n = 718) and lifetime minimal drinkers (n = 1,027) were compared with drinkers across demographics and early‐life characteristics (i.e., religion, poverty, parental education, and family alcohol problems) in logistic regression models.

Results

Using a strict measurement of zero drinks from adolescence to the 50s, only 1.7% of the sample was defined as lifetime abstainer compared to a broader definition allowing a total of 1 drink over the lifetime that included 9.5% and to lifetime minimal drinking (a total of 3 drinks or less a month), which accounted for 13.7%. Factors significantly associated with lifetime abstention and lifetime minimal drinking included religion, poverty, having no family alcohol problems, Hispanic ethnicity, foreign‐born, and female gender. Importantly, work‐related health limitations in early life were significantly associated, but not childhood physical and mental health problems.

Conclusions

Alcohol‐related health studies should utilize lifetime classifications of drinkers and abstainers, and, in doing so, should account for early‐life socioeconomic adversity and childhood health factors or consider these as unmeasured confounders.
Perivascular adipose tissue inflammation in vascular disease
Authors: Nosalski Ryszard , Guzik Tomasz J
Published: January 2017

Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies, perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vaso‐protective adipocyte‐derived relaxing factors and increased production of paracrine factors such as resistin, leptin, cytokines (IL‐6 and TNF‐α) and chemokines [RANTES (CCL5) and MCP‐1 (CCL2)]. These adipocyte‐derived factors initiate and orchestrate inflammatory cell infiltration including primarily T cells, macrophages, dendritic cells, B cells and NK cells. Protective factors such as adiponectin can reduce NADPH oxidase superoxide production and increase NO bioavailability in the vessel wall, while inflammation (e.g. IFN‐γ or IL‐17) induces vascular oxidases and eNOS dysfunction in the endothelium, vascular smooth muscle cells and adventitial fibroblasts. All of these events link the dysfunctional perivascular fat to vascular dysfunction. These mechanisms are important in the context of a number of cardiovascular disorders including atherosclerosis, hypertension, diabetes and obesity. Inflammatory changes in PVAT's molecular and cellular responses are uniquely different from classical visceral or subcutaneous adipose tissue or from adventitia, emphasizing the unique structural and functional features of this adipose tissue compartment. Therefore, it is essential to develop techniques for monitoring the characteristics of PVAT and assessing its inflammation. This will lead to a better understanding of the early stages of vascular pathologies and the development of new therapeutic strategies focusing on perivascular adipose tissue.

Linked Articles

This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc
Elevated semaphorin5A in systemic lupus erythematosus is in association with disease activity and lupus nephritis
Authors: Du Y , Wu X , Chen M , Wang W , Xv W , Ye L , Wu D , Xue J , Sun W , Luo J , Wu H
Published: January 2017

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by extensive immune response, including over-activation of T and B cell development of pathogenic autoantibodies, organ damage induced by the formation and deposition of immune complex and the abnormal elevation of type I interferon. Semaphorin5A (Sema5A) is involved essentially in immune cell regulation and is also implicated in the pathogenesis of autoimmune disorders. We aimed to evaluate the role of Sema5A in patients with SLE. Serum levels of Sema5A were tested by enzyme-linked immunosorbent assay (ELISA) in 152 SLE patients and 48 healthy controls. The message ribonucleic acid (mRNA) expression levels of Sema5A and ADAM metallopeptidase domain 17 (ADAM17) in the peripheral blood mononuclear cells (PBMC) from 43 patients with SLE and 19 healthy controls were detected by the real-time–quantitative polymerase chain reaction (qPCR). Serum Sema5A levels were increased significantly in SLE patients compared with healthy controls (P < 0·001). Elevated levels of Sema5A were correlated positively with 24-h proteinuria excretion (r = 0·558, P < 0·0001), SLE disease activity index (SLEDAI) (r = 0·278, P = 0·0006) and C-reactive protein (CRP) (r = 0·266, P = 0·002), but negatively with planet (PLT) (r = –0·294, P = 0·0003) and complement 3 (C3) (r = –0·287, P = 0·0004) in SLE patients. Patients with elevated Sema5A levels showed higher incidence of rash, serositis and nephritis (P < 0·05 or P < 0·001). Patients with decreased PLT, C3 or positive for proteinuria also showed elevated Sema5A (P < 0·001 or P < 0·05). The mRNA ADAM17 was increased in SLE patients and correlated positively with serum Sema5A levels. Our data demonstrated that elevated serum Sema5A in SLE patients correlated with disease activity and are involved in kidney and blood system damage; ADAM17 might be involved in the release of secreted Sema5A.
Single‐sided deafness affects language and auditory development – a case–control study
Authors: Sangen A. , Royackers L. , Desloovere C. , Wouters J. , van Wieringen A.
Published: January 2017

Objectives

To examine auditory, linguistic and cognitive outcomes of children with single‐sided deafness (SSD). An increasing body of research suggests that children with SSD lag behind with respect to their normal hearing (NH) peers. In this study, we tap into certain developmental skills.

Design

Case–control study.

Participants

Twenty‐one children with SSD between 5 and 15 years of age participated. Per child with SSD, two NH control children were matched on age and gender.

Outcome measures

Morphology, syntax and vocabulary were examined, and performance was assessed in depth by focusing on subskills and type of errors made. Furthermore, tests of short‐term and working memory were conducted, and aspects of hearing disability were assessed by means of the speech spatial and qualities of hearing questionnaire (SSQ).

Main results

The children with SSD lagged behind in their scores on the three language tests and showed some differences to the NH group concerning type of errors and difficulty of the several subskills. Furthermore, scores on the SSQ indicated that in daily life, the children with SSD experience problems in spatial hearing and in understanding speech in noisy situations and that the effort they have to put into listening and in understanding speech is considerably greater than in NH children.

Conclusions

This study showed differences between children with SSD and NH children on several language skills and on auditory behaviour. Possibly, early intervention could prevent such language difficulties and minimise problems with spatial hearing and speech understanding.
Diagnostic accuracy of echocardiography combined with chest CT in pulmonary hypertension
Authors: Shujaat Adil , Bajwa Abubakr A. , Al‐Saffar Farah , Bellardini Jason , Jones Lisa , Cury James D.
Published: January 2017

Background

Transthoracic echocardiography (TTE) and computerized axial tomography (CT) are complementary imaging techniques. It is possible that a combination of the two may offer a better way of identifying pulmonary hypertension (PH) than either one alone.

Objectives

To determine the diagnostic accuracy of TTE combined with chest CT in pulmonary hypertension.

Methods

We performed a retrospective review of consecutive patients who had undergone TTE, CT and right heart catheterization (RHC) between 7/1/2008 and 6/30/2012. PH was defined as systolic pulmonary artery pressure >40 mm Hg or tricuspid regurgitant (TR) jet velocity >2.8m/s on TTE, ratio of diameter of pulmonary artery to ascending aorta (rPA) >1 or diameter of PA (dPA) >30 mm on CT, and mean PAP (mPAP) >25 mm Hg on RHC.

Results

There was a total of 87 patients. The mean ± SD age was 54.3 ± 15.9 years and 69 (79%) were female. The prevalence of PH was 75%. The mean ± SD mPAP was 35.8 ± 14.2 mm Hg. The majority of the patients belonged to World Health Organization group I PH. Fifty per cent of the CT scans were done with intravenous contrast dye. The combination of TR jet velocity and rPA provided the best combination of sensitivity (98%) and specificity (70%) with an ROC area under the curve of 0.84.

Conclusion

The combination of TTE and chest CT is better than either imaging technique alone in identifying patients with PH in a heterogeneous population and may exclude PH
Integrated carbon, sulfur, and nitrogen isotope chemostratigraphy of the Ediacaran Lantian Formation in South China: Spatial gradient, ocean redox oscillation, and fossil distribution
Authors: Wang W. , Guan C. , Zhou C. , Peng Y. , Pratt L. M. , Chen X. , Chen L. , Chen Z. , Yuan X. , Xiao S.
Published: January 2017

The Ediacaran Doushantuo Formation in South China is a prime target for geobiological investigation because it offers opportunities to integrate chemostratigraphic and paleobiological data. Previous studies were mostly focused on successions in shallow‐water shelf facies, but data from deep‐water successions are needed to fully understand basinal redox structures. Here, we report δ13Ccarb, δ13Corg, δ34Spyr, δ34SCAS, and δ15Nsed data from a drill core of the fossiliferous Lantian Formation, which is a deep‐water equivalent of the Doushantuo Formation. Our data confirm a large (>10‰) spatial gradient in δ13Ccarb in the lower Doushantuo/Lantian formations, but this gradient is probably due to the greater sensitivity of carbonate‐poor deep‐water sediments to isotopic mixing with 13C‐depleted carbonate cements. A pronounced negative δ13Ccarb excursion (EN3) in the upper Doushantuo/Lantian formations, however, is spatially consistent and may be an equivalent of the Shuram excursion. δ34Spyr is more negative in deeper‐water facies than in shallow‐water facies, particularly in the lower Doushantuo/Lantian formations, and this spatial pattern is interpreted as evidence for ocean redox stratification: Pyrite precipitated in euxinic deep waters has lower δ34Spyr than that formed within shallow‐water sediments. The Lantian Formation was probably deposited in oscillating oxic and euxinic conditions. Euxinic black shales have higher TOC and TN contents, but lower δ34Spyr and δ15Nsed values. In euxinic environments, pyrite was predominantly formed in the water column and organic nitrogen was predominantly derived from nitrogen fixation or NH4+ assimilation because of quantitative denitrification, resulting in lower δ34Spyr and δ15Nsed values. Benthic macroalgae and putative animals occur exclusively in euxinic black shales. If preserved in situ, these organisms must have lived in brief oxic episodes punctuating largely euxinic intervals, only to be decimated and preserved when the local environment switched back to euxinia again. Thus, taphonomy and ecology were the primary factors controlling the stratigraphic distribution of macrofossils in the Lantian Formation.
Climatic warming strengthens a positive feedback between alpine shrubs and fire
Authors: Camac James S. , Williams Richard J. , Wahren Carl‐Henrik , Hoffmann Ary A. , Vesk Peter A.
Published: January 2017

Climate change is expected to increase fire activity and woody plant encroachment in arctic and alpine landscapes. However, the extent to which these increases interact to affect the structure, function and composition of alpine ecosystems is largely unknown. Here we use field surveys and experimental manipulations to examine how warming and fire affect recruitment, seedling growth and seedling survival in four dominant Australian alpine shrubs. We found that fire increased establishment of shrub seedlings by as much as 33‐fold. Experimental warming also doubled growth rates of tall shrub seedlings and could potentially increase their survival. By contrast, warming had no effect on shrub recruitment, postfire tussock regeneration, or how tussock grass affected shrub seedling growth and survival. These findings indicate that warming, coupled with more frequent or severe fires, will likely result in an increase in the cover and abundance of evergreen shrubs. Given that shrubs are one of the most flammable components in alpine and tundra environments, warming is likely to strengthen an existing feedback between woody species abundance and fire in these ecosystems.
Pollen nutrients better explain bumblebee colony development than pollen diversity
Authors: Moerman Romain , Vanderplanck Maryse , Fournier Denis , Jacquemart Anne‐Laure , Michez Denis
Published: January 2017

Bumblebees are valuable pollinators of numerous wild and cultivated plants. They can forage on variable pollen resources. As some pollen species lack particular nutrients or have global low nutritional quality, it has been suggested that bumblebees mix their pollen incomes to ensure a global balanced diet. The hypothesis that a mixed pollen diet better supports bumblebee colony development than a single pollen diet has been poorly explored.

We compared the impact of mono‐, di‐ and trifloral diets on microcolony development of Bombus terrestris using three pollen resources with different nutrient contents (Cytisus scoparius, Erica sp. and Sorbus aucuparia) as well as their mixes. Nine parameters (e.g. pollen efficacy: total weight of larvae/total weight of pollen collection) were used to compare the microcolony performances. Moreover, we measured the influence of the pollen diversity and nutritional composition on relevant parameters.

We showed that microcolonies can potentially better develop on mixed pollen diets, but single pollen diet can also be as good as mixed pollen diet. Moreover, the sterol concentration appeared as a key factor to establish the impact of a pollen diet on the bumblebee colony development.

This study reveals that diverse pollen diet does not necessary equate with good colony development and supports the importance of selecting floral resources by considering their nutrient contents for bee conservation management.
Exon 2 sequencing of the new HLA‐DRB1 allele, DRB1*13:216
Authors: Planelles D. , Balas A. , Alenda R. , Vicario J. L.
Published: January 2017

A novel HLA‐DRB1*13:216 allele was characterized in a Spanish bone marrow donor.
Novel Mapping Technique for Localization of Focal and Reentrant Activation During Atrial Fibrillation
Authors: TAKAHASHI YOSHIHIDE , IWAI SHINSUKE , YAMASHITA SYU , MASUMURA MAYUMI , SUZUKI MASAHITO , YABE KENTO , SATO YASUHIRO , HIRAO KENZO , ISOBE MITSUAKI
Published: January 2017

Novel Mapping Technique for AF

Introduction

Identification of wavefront propagation pattern during AF remains challenging in ablation procedures. We sought to test a novel combination of a new mapping technology called Ripple Map and high‐density mapping to distinguish focal and reentrant activation during atrial fibrillation (AF).

Methods and Results

Subjects were patients undergoing ablation for persistent AF. If AF remained after isolation of the pulmonary veins, the left atrium (LA) was mapped by a high‐density mapping catheter for later analysis, after which ablation was continued using a conventional stepwise approach. After the procedure, electrograms from the high‐density mapping catheter were analyzed using Ripple Map, which is a new feature in the CARTO®3, and type of activation on ≥3 consecutive AF cycles was determined. High‐density mapping was performed on 569 sites in 45 patients (13 ± 3 sites per patient). AF wavefront propagation determined by Ripple Map was in good agreement with analysis of manual annotation of bipolar electrograms. Ripple Map's representation of wavefront activation pattern, which could include local as well as far‐field activity, allowed us to identify focal activation in 64 (11%) sites and 1 (0.2%) reentrant activation site. Radiofrequency delivery in atrial regions with activation sites identified as focal by Ripple Map resulted in termination of AF more often than regions without focal activation (22% vs. 7%, P = 0.015).

Conclusion

This study demonstrated that Ripple Map enabled quick identification of AF wavefront activation pattern, potentially being helpful for determining ablation targets in persistent AF.
Hybrid Minimally Invasive Approach for Transvenous Lead Extraction: A Feasible Technique in High‐Risk Patients
Authors: BONTEMPI LUCA , VASSANELLI FRANCESCA , CERINI MANUEL , BISLERI GIANLUIGI , REPOSSINI ALBERTO , GIROLETTI LAURA , INAMA LORENZA , SALGHETTI FRANCESCA , LIBERTO DARIA , GIACOPELLI DANIELE , RAWEH ABDALLAH , MUNERETTO CLAUDIO , CURNIS ANTONIO
Published: January 2017

Hybrid Approach for Lead Extraction

Introduction

Despite the overall safety, transvenous lead extraction (TLE) remains a challenging procedure with inherent risks, where surgery can still be required in elective cases. In this study, we report our experience with a minimally invasive “hybrid” approach, defined as a procedure performed by an electrophysiologist with the support of a cardiac surgeon in the same operative session.

Methods and Results

We reported 12 cases of planned hybrid lead extraction; minithoracotomy and thoracoscopy were performed on 10 (83%) and 2 (17%) patients, respectively. A total of 25 leads out of 27 (median lead age 19 years) were successfully extracted with laser, mechanical or combined transvenous sheath. In 3 patients, the direct monitoring of vascular and myocardial integrity allowed for prompt treatment of potential vascular injury during the lead extraction maneuvers. Mean in‐hospital stay was 4 ± 2 days. There were no major intraoperative complications and no deaths occurred after 30 days' follow‐up.

Conclusion

The hybrid approach, with minithoracotomy or thoracoscopy, is feasible and it might increase the safety in the most challenging TLE procedures: the minimally invasive surgical intervention allows for continuous monitoring of the critical cardiac structures and prompt treatment of potential complications.
Effects of 1,25(OH)2D3 and vitamin D receptor on peripheral CD4+/CD8+ double‐positive T lymphocytes in a mouse model of systemic lupus erythematosus
Authors: Ding Yan , Liao Wang , He Xiao‐Jie , Xiang Wei
Published: January 2017

This study aims to explore effects of 1,25(OH)2D3 and vitamin D receptor (VDR) on peripheral CD4+/CD8+ double‐positive (DP) T lymphocytes in systemic lupus erythematosus (SLE). MRL‐LPr/LPr mice with SLE (n = 20) and normal MRL mice (n = 20) were assigned into the control group (normal mice, without feeding with 1,25(OH)2D3), the 1,25(OH)2D3 group (SLE mice, feeding with 1,25(OH)2D3), the VDR‐knock‐in + 1,25(OH)2D3 group (SLE mice, VDR‐knock‐in, feeding with 1,25(OH)2D3) and the VDR‐knockout group (normal mice, VDR‐knockout, without feeding with 1,25(OH)2D3) (n = 10 per group). Levels of T lymphocytes were measured by flow cytometry. The mRNA and proteins expressions of inflammatory factors were measured by qRT‐PCR and ELISA. Extracellular signal‐regulated kinase‐1/2 (ERK1/2) expression was measured by Western blotting. Compared with normal mice, SLE mice showed reduced levels of CD4+, CD4+/CD8+ ratio, and DP lymphocytes. The levels of SLE‐related indicators all increased significantly, followed with severe skin ulcers and urinary system infection. With the increase in time, skin ulcers and urinary system infection were significantly improved, levels of CD4+, CD4+/CD8+ ratio, and DP lymphocytes increased, and levels of SLE‐related indicators all decreased in the 1,25(OH)2D3 group. There were no significant changes in bioindicators in the control and the VDR‐knock‐in + 1,25(OH)2D3 groups. The symptoms of SLE gradually occurred in the VDR‐knockout group. This study demonstrates that VDR and 1,25(OH)2D3 could elevate CD4+/CD8+ DP T lymphocytes and reduce expressions of inflammatory factors, thus inhibiting the development and progression of SLE.
Comparative 3D micro‐CT and 2D histomorphometry analysis of dental implant osseointegration in the maxilla of minipigs
Authors: Bissinger Oliver , Probst Florian Andreas , Wolff Klaus‐Dietrich , Jeschke Anke , Weitz Jochen , Deppe Herbert , Kolk Andreas
Published: January 2017

Aim

The bone implant contact (BIC) has traditionally been evaluated with histological methods. Thereupon, strong correlations of two‐dimensional (2D) BIC have been detected between μCT and destructive histology. However, due to the high intra‐sample variability in BIC values, one histological slice is not sufficient to represent 3D BIC. Therefore, our aim has been to correlate the averaged values of 3–4 histological sections to 3D μCT.

Material and Methods

Fifty‐four implants inserted into the maxilla of 14 minipigs were evaluated. Two different time points were selected to assess the 3D BIC (distance to implant: 2–5 voxels), an inner ring (6–30 voxels) and an outer ring (55–100 voxels) using μCT (voxel size: 10 μm) and to correlate the values to histomorphometry.

Results

Strong correlations (p < 0.0001; 28 days, 56 days, total) were seen between μCT and histomorphometry concerning BIC (r = 0.84, r = 0.85, r = 0.83), the inner ring (r = 0.87, r = 0.87, r = 0.88) and the outer ring (r = 0.85, r = 0.85, r = 0.88). Closer to the implant, μCT values were higher compared with histomorphometry.

Conclusion

Although 3–4 histological slices per implant seem to predict the 3D BIC, μCT might be advantageous because of its non‐destructive 3D character. The healing time may not impact on the comparability.
Influence of protein fermentation and carbohydrate source on in vitro methane production
Authors: Vanegas J. L. , González J. , Carro M. D.
Published: January 2017

Incubations were carried out with batch cultures of ruminal micro‐organisms from sheep to analyse the influence of the N source on in vitro CH4 production. The two substrates were mixtures of maize starch and cellulose in proportions of 75:25 and 25:75 (STAR and CEL substrates, respectively), and the three nitrogen (N) sources were ammonia (NH4Cl), casein (CA) and isolated soya bean protein (SP). Five isonitrogenous treatments were made by replacing non‐protein‐N (NPN) with CA or SP at levels of 0 (NPN), 50 (CA50 and SP50, respectively) and 100% (CA100 and SP100) of total N. All N treatments were applied at a rate of 35 mg of N/g of substrate organic matter and incubations lasted 16.5 h. With both proteins, N source × substrate interactions (p = 0.065 to 0.002) were detected for CH4 production and CH4/total VFA ratio. The increases in CH4 production observed by replacing the NPN with protein‐N were higher (p < 0.05) for STAR than for CEL substrate, but the opposite was observed for the increases in volatile fatty acid (VFA) production. As a consequence, replacing the NPN by increased levels of CA or SP led to linear increases (p < 0.05) in CH4/total VFA ratio with STAR, whereas CH4/total VFA ratio tended (p < 0.10) to be decreased with CEL substrate. Increasing the amount of both proteins decreased linearly (p < 0.05) ammonia‐N concentrations, which may indicate an incorporation of amino acids and peptides into microbial protein without being first deaminated into ammonia‐N. In incubations with the tested N sources as the only substrate, the fermentation of 1 mg of CA or SP produced 1.24 and 0.60 μmol of CH4 respectively. The results indicate the generation of CH4 from protein fermentation, and that the response of CH4 production to protein‐N supply may differ with the basal substrate.
Effect of laboratory‐isolated Lactobacillus plantarum LGFCP4 from gastrointestinal tract of guinea fowl on growth performance, carcass traits, intestinal histomorphometry and gastrointestinal microflora population in broiler chicken
Authors: Vineetha P. G. , Tomar S. , Saxena V. K. , Kapgate M. , Suvarna A. , Adil K.
Published: January 2017

The study aimed to investigate the effect of feed supplements, viz Lactobacillus plantarum LGFCP4 (laboratory isolate from GIT of Guinea fowl), Lactobacillus acidophilus (NCDC, Karnal) and in‐feed antibiotic bacitracin methylene disalicylate (BMD) on growth performance, FCR, carcass traits and immune organs weight, intestinal histomorphometry and gastrointestinal microflora population in broiler chickens. In a completely randomized design, CARIBRO‐Dhanraja broiler chicks (n = 160) were used with four treatment groups. During the entire experimental duration of 35 days, treatment groups were provided with different dietary treatments (T1 – basal diet (negative control), T2 – antibiotic growth promoter BMD 20 g/100 kg feed (positive control), T3 – 1 × 108 cfu of L. acidophilus/gm‐fermented feed +MOS 1 g/kg feed and T4 – 1 × 108 cfu of laboratory‐isolated L. plantarum LGFCP4/gm‐fermented feed+ MOS 1 g/kg feed. After 35 days of experimental period, no significant results have been observed in different growth performance traits among treatment groups. Cut‐up parts and edible organs' weight remained unaffected by dietary supplementation, whereas weight of immune organs were significantly higher (p < 0.05) in L. plantarum LGFCP4‐supplemented group. At the end of feeding trial, significantly (p < 0.05) lower E. coli count was observed in crop of T4 birds, while in ileum, T2 and T3 showed lower count. In caeca, T2 group showed lowest E. coli count. Salmonella count in crop and ileum was significantly (p < 0.05) low in T3 and T4, while in caeca, T2 group showed lowest count. In terms of histomorphometry, duodenal villous height (VH), crypt depth (CD) and VH:CD ratio were higher for T3 and T4 and lowest values were obtained for T2 group. The results of the study showed that L. plantarum LGFCP4 isolated from GIT of guinea fowl can effectively replace in‐feed antibiotic growth promoters in broiler diets by altering intestinal villi morphology and improving the gut health by reducing the pathogenic microbial load.
Effects of dietary butyrate supplementation on intestinal integrity of heat‐stressed cockerels
Authors: Abdelqader A. M. , Abuajamieh M. , Hammad H. M. , Al‐Fataftah A.‐R. A.
Published: January 2017

Butyrate modulates intestinal epithelial cell structure and function. Three hundred and sixty Lohmann LSL‐Classic layer cockerels were used to investigate the effect of butyrate on heat stress‐induced intestinal injury and intestinal integrity. The experiment was conducted from day 85 to 105 of age. The birds were divided randomly into three treatments: control, heat stress (HS), and heat stress provided with butyrate (HSB) at a level of 0.35 g/kg of diet. The control was reared at 21 ± 1 °C throughout the experiment. The HS and HSB treatments were exposed to a cyclic HS (35 ± 1 °C from 09:00 to 13:00 and 21 ± 1 °C from 13:00 to 09:00). Intestinal and mucosal weights, villus height, villus surface area (VSA), absorptive epithelial cell area and intestinal beneficial bacteria were lower in the HS treatment than in the other two treatments (p < 0.05). Heat‐stressed cockerels exhibited the highest (p < 0.05) villi injury scores and serum endotoxin levels compared with the other treatments. Dietary inclusion of butyrate increased (p < 0.05) intestinal and mucosal weights, villus height, VSA, absorptive epithelial cell area and intestinal beneficial bacteria counts and reduced (p < 0.05) HS‐induced injury in intestinal epithelia as well as intestinal permeability to endotoxin. In conclusion, dietary butyrate exerted protective effects against intestinal damage induced by HS and improved intestinal health and integrity.