bluuebunny/crossref_metadata_2025 huggingface dataset:
A Resource for the Allele-Specific Analysis of DNA Methylation at Multiple Genomically Imprinted Loci in Mice
Authors: Wasson Jadiel A. , Birol Onur , Katz David J.
Published: July 2017

Genomically imprinted loci are expressed mono-allelically dependent upon the parent of origin. Their regulation not only illuminates how chromatin regulates gene expression but also how chromatin can be reprogrammed every generation. Because of their distinct parent of origin regulation, analysis of imprinted loci can be difficult. Single nucleotide polymorphisms (SNPs) are required to accurately assess these elements allele-specifically. However, publicly available SNP databases lack robust verification, making analysis of imprinting difficult. In addition, the allele-specific imprinting assays that have been developed employ different mouse strains, making it difficult to systemically analyze these loci. Here, we have generated a resource that will allow the allele-specific analysis of many significant imprinted loci in a single hybrid strain ofMus musculus. This resource includes verification of SNPs present within ten of the most widely used imprinting control regions and allele-specific DNA methylation assays for each gene in a C57BL/6J and CAST/EiJ hybrid strain background.
Three-dimensional single cell patterning for mid- to high-throughput studies of tumor cell and extracellular matrix heterogeneity
Authors: Gong Xiangyu , Mills Kristen L.
Published: July 2017

Cancer heterogeneity includes cancer cell genetic heterogeneity and heterogeneity in the tumor microenvironment (TME)—both stromal cells and extracellular matrix (ECM). Determining which combinations of the vast array of possibly interacting heterogeneities drive tumor progression presents a major multi-disciplinary challenge in cancer research. To make effective treatment decisions this challenge must be addressed. The practical challenge is assessing cellular heterogeneity in a statistically powerful way with respect to targeted TME characteristics. Here we present a simple, but extensible, and low-cost method for conducting mid- to high-throughput and long-term studies of heterogeneous cell responses to various biomechanical stimuli in 3D models mimicking the biomechanical properties of the ECM. Using a platform we term “the drop-patterning chip” thousands of cells are simultaneously transferred from microwells and fully embedded, only using the force of gravity, in precise patterns in 3D. This method allows for throughputs approaching flow-through methods, which lack phenotypic information on cell-matrix interactions, and does not rely on expensive or harsh patterning forces, which often times also result in a proximal stiff surface.
Disequilibrium of fire-prone forests sets the stage for a rapid decline in conifer dominance during the 21stcentury
Authors: Serra-Diaz Josep M. , Maxwell Charles , Lucash Melissa S. , Scheller Robert M. , Laflower Danelle M. , Miller Adam D. , Tepley Alan J. , Epstein Howard E. , Anderson-Teixeira Kristina J. , Thompson Jonathan R
Published: July 2017

As trees are long-lived organisms, the impacts of climate change on forest communities may not be apparent on the time scale of years to decades. While lagged responses to environmental change are common in forested systems, potential for abrupt transitions under climate change may occur in environments where alternative vegetation states are influenced by disturbances, such as fire. The Klamath mountains (northern California and southwest Oregon, USA) are currently dominated by carbon rich and hyper-diverse temperate conifer forests, but climate change could disrupt the mechanisms promoting forest stability– regeneration and fire tolerance— via shifts in the fire regime in conjunction with lower fitness of conifers under a hotter climate. Understanding how this landscape will respond to near-term climate change (before 2100) is critical for predicting potential climate change feedbacks and to developing sound forest conservation and management plans. Using a landscape simulation model, we estimate that 1/3 of the Klamath could transition from conifer forest to shrub/hardwood chaparral, triggered by an enhanced fire activity coupled with lower post-fire conifer establishment. Such shifts were more prevalent under higher climate change forcing (RCP 8.5) but were also simulated under the climate of 1950-2000, reflecting the joint influences of early warming trends and historical forest legacies. Our results demonstrate that there is a large potential for loss of conifer forest dominance—and associated carbon stocks and biodiversity- in the Klamath before the end of the century, and that some losses would likely occur even without the influence of climate change. Thus, in the Klamath and other forested landscapes subject to similar feedback dynamics, major ecosystem shifts should be expected when climate change disrupts key stabilizing feedbacks that maintain the dominance of long-lived, slowly regenerating trees.
Long-term community change through multiple rapid transitions in a desert rodent community
Authors: Christensen Erica M. , Harris David J. , Ernest S. K. Morgan
Published: July 2017

While studies increasingly document long-term change in community composition, whether long-term change occurs gradually or via rapid reorganization events remains unclear. We used Latent Dirichlet Allocation (LDA) and a change-point model to examine the long-term dynamics of a desert rodent community undergoing compositional change over a 38-year span. Our approach detected three rapid reorganization events, where changes in the relative abundances of dominant and rare species occurred, and a separate period of increased variance in the structure of the community. These events coincided with time periods—possibly related to climate events—where the total abundance of rodents was extremely low. There are a variety of processes that could link low abundance events with a higher probability of rapid ecological transitions, including higher importance of stochastic processes (i.e., competitive interactions or priority effects) and the removal of structuring effects of competitive dominants or incumbent species. Continued study of the dynamics of community change will provide important information not only on the processes structuring communities, but will also provide guidance for forecasting how communities will undergo change in the future.
Dark period transcriptomic and metabolic profiling of two diverseEutrema salsugineumaccessions
Authors: Yin Jie , Gosney Michael J. , Dilkes Brian P. , Mickelbart Michael V.
Published: July 2017

Eutrema salsugineumis a model species for the study of plant adaptation to abiotic stresses. Two accessions ofE. salsugineum, Shandong (SH) and Yukon (YK), exhibit contrasting morphology, biotic, and abiotic stress tolerance. Transcriptome and metabolic profiling from tissue samples collected during the dark period were used to investigate the molecular and metabolic bases of these contrasting phenotypes. RNA sequencing identified 17,888 expressed genes, of which 157 were not in the published reference genome and 65 were detected for the first time. Differential expression was detected for only 31 genes. The RNA sequencing data contained 14,808 single nucleotide polymorphisms (SNPs) in transcripts, 3,925 of which are newly identified. Among the differentially expressed genes, there were no obvious candidates for the physiological or morphological differences between SH and YK. Metabolic profiling indicated that YK accumulates free fatty acids and long-chain fatty acid derivatives as compared to SH; whereas sugars are more abundant in SH. Metabolite levels suggest that carbohydrate and respiratory metabolism, including starch degradation, is more active during the first half of the dark period in SH. These metabolic differences may explain the greater biomass accumulation in YK over SH. The accumulation of 56% of the identified metabolites was lower in F1hybrids than the mid-parent averages and the accumulation of 17% of the metabolites in F1plants transgressed the level in both parents. Concentrations of several metabolites in F1hybrids agree with previous studies and suggest a role for primary metabolism in heterosis. The improved annotation of theE. salsugineumgenome and newly-identified high-quality SNPs will permit accelerated studies using the standing variation in this species to elucidate the mechanisms of its diverse adaptations to the environment.
Interferon Regulatory Factor 5 (IRF5) Interacts with the Translation Initiation Complex and Promotes mRNA Translation During the Integrated Stress Response to Amino Acid Deprivation
Authors: Warner James D. , Wiley Mandi , Wu Ying-Y , Wen Feng , Kinter Michael , Yanagiya Akiko , Tessneer Kandice L. , Gaffney Patrick M.
Published: July 2017

Interferon Regulatory Factor 5 (IRF5) plays an important role in limiting pathogenic infection and tumor development. Host protection by IRF5 can occur through a variety of mechanisms including production of type I interferon and cytokines as well as the regulation of cell survival, growth, proliferation, and differentiation. While modulation of these cellular processes is attributed to IRF5 transcription factor function in the nucleus, emerging evidence suggests that IRF5 may also retain non-transcriptional regulatory properties within the cytoplasmic compartment. Consistent with this notion, we report the ability of IRF5 to control gene expression at the level of mRNA translation. Our findings demonstrate that IRF5 interacts with the translation initiation complex in the absence of the m7GTP cap-binding protein, eIF4E. We observed that under nutrient deprivation-induced cell stress, IRF5 promoted mRNA translation of the master integrated stress response (ISR) regulator, Activating Transcription Factor 4 (ATF4). Enhanced ATF4 protein expression correlated with increased levels of downstream target genes including CHOP and GADD34 and was associated with amplification of eIF2α de-phosphorylation and translational de-repression under stress. The novel mechanism we describe broadens our understanding of how IRF5 regulates gene expression and may govern diverse cellular processes in the absence of stimuli that trigger IRF5 nuclear translocation.
Evidence of signaling and adhesion roles for β-catenin in the sponge Ephydatia muelleri
Authors: Schippers Klaske J. , Nichols Scott A.
Published: July 2017

β-catenin acts as a transcriptional co-activator in the Wnt/β-catenin signaling pathway and a cytoplasmic effector in cadherin-based cell adhesion. These functions are ancient within animals, but the earliest steps in β-catenin evolution remain unresolved due to limited data from key lineages – sponges, ctenophores and placozoans. Previous studies in sponges have characterized β-catenin expression dynamics and used GSK3B antagonists to ectopically activate the Wnt/β-catenin pathway; both approaches rely upon untested assumptions about the conservation of β-catenin function and regulation in sponges. Here, we test these assumptions using an antibody raised against β-catenin from the spongeEphydatia muelleri. We find that cadherin-complex genes co-precipitate with endogenousEmβ-catenin from cell lysates, but that Wnt pathway components do not. However, through immunostaining we detect both cell boundary and nuclear populations, and we find evidence thatEmβ-catenin is a conserved substrate of GSK3B. Collectively, these data support conserved roles forEmβ-catenin in both cell adhesion and Wnt signaling. Additionally, we find evidence for anEmβ-catenin population associated with the distal ends of F-actin stress fibers in apparent cell-substrate adhesion structures that resemble focal adhesions. This finding suggests a fundamental difference in the adhesion properties of sponge tissues relative to other animals, in which the adhesion functions of β-catenin are typically restricted to cell-cell adhesions.
Tissue Folding by Mechanical Compaction of the Mesenchyme
Authors: Hughes Alex J. , Miyazaki Hikaru , Coyle Maxwell C. , Zhang Jesse , Laurie Matthew T. , Chu Daniel , Vavrušová Zuzana , Schneider Richard A. , Klein Ophir D. , Gartner Zev J.
Published: July 2017

Many tissues fold during development into complex shapes. Engineering this process in vitro would represent an important advance for tissue engineering. We use embryonic tissue explants, finite element modeling, and 3D cell patterning techniques to show that a mechanical compaction of the ECM during mesenchymal condensation can drive tissue folding along programmed trajectories. The process requires cell contractility, generates strains at nearby tissue interfaces, and causes specific patterns of collagen alignment around and between condensates. Aligned collagen fibers support elevated tensions that promote the folding of interfaces along paths that can be predicted by finite element modeling. We demonstrate the robustness and versatility of this strategy for sculpting tissue interfaces by directing the morphogenesis of a variety of folded tissue forms from engineered patterns of mesenchymal condensates. These studies provide insight into the active mechanical properties of the embryonic mesenchyme and establish entirely new strategies for more robustly directing tissue morphogenesisex vivo,without genetic engineering.
Resurrecting ancestral genes in bacteria to interpret ancient biosignatures
Authors: Kacar Betul , Guy Lionel , Smith Eric , Baross John
Published: July 2017

Two datasets, the geologic record and the genetic content of extant organisms, provide complementary insights into the history of how key molecular components have shaped or driven global environmental and macroevolutionary trends. Changes in global physicochemical modes over time are thought to be a consistent feature of this relationship between Earth and life, as life is thought to have been optimizing protein functions for the entirety of its ∼3.8 billion years of history on Earth. Organismal survival depends on how well critical genetic and metabolic components can adapt to their environments, reflecting an ability to optimize efficiently to changing conditions. The geologic record provides an array of biologically independent indicators of macroscale atmospheric and oceanic composition, but provides little in the way of the exact behavior of the molecular components that influenced the compositions of these reservoirs. By reconstructing sequences of proteins that might have been present in ancient organisms, we can identify a subset of possible sequences that may have been optimized to these ancient environmental conditions. How can extant life be used to reconstruct ancestral phenotypes? Configurations of ancient sequences can be inferred from the diversity of extant sequences, and then resurrected in the lab to ascertain their biochemical attributes. One way to augment sequence-based, single-gene methods to obtain a richer and more reliable picture of the deep past, is to resurrect inferred ancestral protein sequences in living organisms, where their phenotypes can be exposed in a complex molecular-systems context, and to then link consequences of those phenotypes to biosignatures that were preserved in the independent historical repository of the geological record. As a first-step beyond single molecule reconstruction to the study of functional molecular systems, we present here the ancestral sequence reconstruction of the beta-carbonic anhydrase protein. We assess how carbonic anhydrase proteins meet our selection criteria for reconstructing ancient biosignatures in the lab, which we term paleophenotype reconstruction.
Resting-state connectivity and its association with cognitive performance, educational attainment, and household income in UK Biobank (N = 3,950)
Authors: Shen Xueyi , Cox Simon R , Adams Mark J , Howard David M , Lawrie Stephen M , Ritchie Stuart J , Bastin Mark E , Deary Ian J , McIntosh Andrew M , Whalley Heather C
Published: July 2017

Cognitive ability is an important predictor of lifelong physical and mental well-being and its impairments are associated with many psychiatric disorders. Higher cognitive ability is also associated with greater educational attainment and increased household income. Understanding neural mechanisms underlying cognitive ability is therefore of crucial importance for determining the nature of these associations. In the current study, we examined the spontaneous activity of the brain at rest to investigate its relationships with not only cognitive ability, but also educational attainment and household income. We used a large sample of resting-state neuroimaging data from UK Biobank (N=3,950). Firstly, analysis at the whole-brain level showed that connections involving the default mode network (DMN), fronto-parietal network (FPN) and cingulo-opercular network (CON) were significantly positively associated with levels of cognitive performance assessed by a verbal-numerical reasoning test (standardised β ranged from 0.054 to 0.097). Connections associated with higher levels of cognitive performance were also significantly positively associated with educational attainment (r=0.48, N=4,160) and household income (r=0.38, N=3,793). Further, analysis on the coupling of functional networks showed that better cognitive performance was associated with more positive DMN-CON connections, decreased cross-hemisphere connections between homotopic network in CON and FPN, and stronger CON-FPN connections (absolute β ranged from 0.034 to 0.063). The present study finds that variation in brain resting state functional connectivity associated with individual differences in cognitive ability, largely involving DMN and lateral prefrontal networks. Additionally, we provide further evidence of shared neural associations of cognitive ability, educational attainment, and household income.
Exploration of Western Himalayan region for identification of gold nanoparticles synthesizing bacteria
Authors: Thakur Rajni Kant , Shirkot Poonam
Published: July 2017

The development of eco-friendly methods for the synthesis of nanomaterial shape and size is an important area of research in the field of nanotechnology. In present study an indigenous bacterial strain GPI-1 has been isolated from a local gold mine Khaltunala. It was characterized morphological, biochemically and also by using 16S rrna gene technology and was identified asBacillus flexusGPI-1, the phylogeny of this bacterial strain was determined using various bioinformatics tools viz BLASTn and MEGA 5.0. To achieve maximuminvitrogold nanoparticles synthesis various parameters such as pH, incubation temperature, incubation time period and wavelength were optimized as 6.8, 37°C, 36 hrs, 560 nm respectively. Stable and cubical gold nanoparticles (GNPs) formation with 40-45 nm dimensions were synthesized successfully underinvitroconditions upon exposure of gold chloride trihydrates (HAuCl4) solution to the supernatant ofBacillus flexusstrain GPI-1. These gold nanoparticles have been characterized by Transmission electron microscope, Fourier transform infrared spectroscopy (FTIR). Thus in the present study successful biosynthesis method of stable and cubical gold nanoparticles in the size range of 12-30 nm using this efficientBacillus flexusGPI-1 strain. Thus in the present study leading to development of an easy bioprocess for synthesis of GNPs of desired size and shape, has been reported and this green route of biosynthesis of GNPs is a simple, economically viable and an eco-friendly process. The use of gold nanoparticles in biomedical research like X-ray computed tomography and magnetic resonance imaging, cancer research, drug delivery applications.
Dependence of Intravoxel Incoherent Motion diffusion MR thresholdb-value selection for separating perfusion and diffusion compartments and liver fibrosis diagnostic performance
Authors: Li Yao , Lu Pu-Xuan , Huang Hua , Leung Jason , Chen Weitian , Wang Yi-Xiang
Published: July 2017

Purpose

To explore how the selection of thresholdb-value impacts Intravoxel Incoherent Motion (IVIM) diffusion parameters of PF (f), Dslow(D),and Dfast(D*) values and their performance for liver fibrosis detection.

Materials and Methods

Fifteen healthy volunteers and 33 hepatitis-b patients were included. With a 1.5 T MR scanner and respiration gating, IVIM data was acquired with 10b-values of 10,20,40,60,80,100,150, 200, 400, and 800 s/mm2. Signal measurement was performed on right liver. Segmented-unconstrained analysis was used to compute IVIM parameters, and six thresholdb-values between 40 and 200 s/mm2were compared. PF, Dslow, and Dfast values were placed along thex-axis,y-axis, andz-axis, and a plane was defined to separate volunteers from patients.

Results

Higher thresholdb-values were associated with higher PF measurement; while lower thresholdb-values led to higher Dslow and Dfast measurements. The dependence of PF, Dslow, and Dfast on thresholdb-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Thresholdb-value=60 s/mm2showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints in 3-dimensional space.

Conclusion

For segmented-unconstrained analysis, the selection of thresholdb-value=60 s/mm2improves IVIM diffusion differentiation between healthy livers and fibrotic livers.
A mathematical model relates intracellular TLR4 oscillations to sepsis progression
Authors: Stan Razvan C. , Soriano Francisco G. , de Camargo Maristela M.
Published: July 2017

Oscillations drive many biological processes and their modulation is determinant for various pathologies. In sepsis syndrome, Toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its expression and activity, along with its intracellular trafficking rates shift the equilibrium between the pro‐ and anti-inflammatory downstream signaling cascades, leading to either the physiological resolution of the bacterial stimulation or to sepsis. We hypothesize that the initialtlr4expression in patients diagnosed with sepsis and TLR4 dynamic concentration changes on the cell membrane or intracellularly, dictates how the sepsis syndrome is initiated. Using a set of three differential equations, we defined the TLR4 flux between relevant cell organelles. We obtained three different regions in the phase space: 1. a limit-cycle describing unstimulated physiological oscillations, 2. a fixed-point attractor resulting from moderate LPS stimulation that is resolved and 3. a double-attractor resulting from sustained LPS stimulation that leads to sepsis. We tested the models against hospital data of sepsis patients and we correctly evaluate the clinical outcome of these patients.
A phylogenetic and evolutionary analysis of antimycin biosynthesis
Authors: Joynt Rebecca , Seipke Ryan F.
Published: July 2017

Streptomycesspecies and otherActinobacteriaare ubiquitous in diverse environments worldwide and are the source of, or inspiration for, the majority of pharmaceuticals. The genomic era has enhanced biosynthetic understanding of these valuable chemical entities and has also provided a window into the diversity and distribution of natural product biosynthetic gene clusters. Antimycin is an inhibitor of mitochondrial cytochrome c reductase and more recently was shown to inhibit Bcl-2/Bcl-XLsrelated anti-apoptotic proteins commonly overproduced by cancerous cells. Here we identify 65 putative antimycin biosynthetic gene clusters (BGCs) in publicly available genome sequences ofActinobacteriaand classify them based on the presence or absence of cluster-situated genesantPandantQ,which encode a kynureninase and phosphopantetheinyl transferase (PPTase), respectively. The majority of BGCs possess either bothantPandantQ(L-form) or neither (S-form), while a minority of them lack eitherantPorantQ(IQor IPform, respectively). We also evaluate the biogeographical distribution and phylogenetic relationships of antimycin producers and BGCs. We show that antimycin BGCs occur on five of the seven continents and are frequently isolated from plants and other higher organisms. We also provide evidence for two distinct phylogenetic clades of antimycin producers and gene clusters, which delineate S-form from L- and I-form BGCs. Finally, our findings suggest that the ancestral antimycin producer harboured an L-form gene cluster which was primarily propagated by vertical transmission and subsequently diversified into S-, IQand IPform biosynthetic pathways.
Cytosolic proteins can exploit membrane localization to trigger functional assembly
Authors: Yogurtcu Osman N. , Johnson Margaret E.
Published: July 2017

Cell division, endocytosis, and viral budding would not function without the localization and assembly of protein complexes on membranes. What is poorly appreciated, however, is that by localizing to membranes, proteins search in a reduced space that effectively drives up concentration. Here we derive an accurate and practical analytical theory to quantify the significance of this dimensionality reduction in regulating protein assembly on membranes. We define a simple metric, an effective equilibrium constant, that allows for quantitative comparison of protein-protein interactions with and without membrane present. To test the importance of membrane localization for driving protein assembly, we collected the protein-protein and protein-lipid affinities, protein and lipid concentrations, and volume-to-surface-area ratios for 46 interactions between 37 membrane-targeting proteins in human and yeast cells. We find that many of the protein-protein interactions between pairs of proteins involved in clathrin-mediated endocytosis in human and yeast cells can experience enormous increases in effective protein-protein affinity (10-1000 fold) due to membrane localization. Localization of binding partners thus triggers robust protein complexation, suggesting that it can play an important role in controlling the timing of endocytic protein coat formation. Our analysis shows that several other proteins involved in membrane remodeling at various organelles have similar potential to exploit localization. The theory highlights the master role of phosphoinositide lipid concentration, the volume-to-surface-area ratio, and the ratio of 3D to 2D equilibrium constants in triggering (or preventing) constitutive assembly on membranes. Our simple model provides a novel quantitative framework for interpreting or designingin vitroexperiments of protein complexation influenced by membrane binding.
Physical activity unveils the relationship between mitochondrial energetics, muscle quality and physical function in older adults
Authors: Distefano Giovanna , Standley Robert A. , Zhang Xiaolei , Carnero Elvis A. , Yi Fanchao , Cornnell Heather H. , Coen Paul M.
Published: July 2017

Background

The concept of mitochondrial dysfunction in aging muscle is highly controversial. In addition, emerging evidence suggests that reduced muscle oxidative capacity and efficiency underlie the etiology of mobility loss in older adults. Here, we hypothesized that studying well phenotyped older cohorts across a wide range of physical activity would unveil a range of mitochondrial function in skeletal muscle and in turn allow us to more clearly examine the impact of ageper seon mitochondrial energetics. This also enabled us to more clearly define the relationships between mitochondrial energetics and muscle lipid content with clinically relevant assessments of muscle and physical function.

Methods

Thirty-nine volunteers were recruited to the following study groups; Young Active (YA, n=2F/8M, age=31.2±5.4 yrs.). Older Active (OA, n=2F/8M, age=67.5±2.7 yrs.) and Older Sedentary (OS, n=8F/11M, age=70.7±4.7 yrs.). Participants completed a graded exercise test to determine fitness (VO2peak), a submaximal exercise test to determine exercise efficiency, and daily physical activity (PA) was recorded using a tri-axial armband accelerometer. Mitochondrial energetics were determined by 1) 31P magnetic resonance spectroscopy and 2) respirometry of fiber bundles from vastus lateralis biopsies. Quadriceps function was assessed by isokinetic dynamometry and physical function by the short physical performance battery (SPPB) and stair climb test.

Results

Daily PA energy expenditure was significantly lower in OS, compared to YA and OA groups. Despite fitness being higher in YA compared to OA and OS, mitochondrial respiration, ATPMax, P/O ratio and exercise efficiency were similar in YA and OA groups and were significantly lower in OS. P/O ratio was correlated with exercise efficiency. Time to complete the stair climb and repeated chair stand tests was significantly greater for OS. Interestingly, ATPMax was related to muscle contractile performance and physical function.

Conclusions

Older adults who maintain a high amount of physical activity have better mitochondrial capacity, similar to highly active younger adults, and this is related to their better muscle quality, exercise efficiency and physical performance. This suggests that mitochondria could be an important therapeutic target for sedentary aging associated conditions including sarcopenia, dynapenia and loss of physical function.
Characterization of a set of abdominal neuroendocrine cells that regulate stress physiology using colocalized diuretic peptides inDrosophila
Authors: Zandawala Meet , Marley Richard , Davies Shireen A. , Nässel Dick R.
Published: July 2017

Multiple neuropeptides are known to regulate water and ion balance inDrosophila melanogaster. Several of these peptides also have other functions in physiology and behavior. Examples are corticotropin-releasing factor-like diuretic hormone (diuretic hormone 44; DH44) and leucokinin (LK), both of which induce fluid secretion by Malpighian tubules (MTs), but also regulate stress responses, feeding, circadian activity and other behaviors. Here, we investigated the functional relations between the LK and DH44 signaling systems. DH44 and LK peptides are only colocalized in a set of abdominal neurosecretory cells (ABLKs). Targeted knockdown of each of these peptides in ABLKs leads to increased resistance to desiccation, starvation and ionic stress. Food ingestion is diminished by knockdown of DH44, but not LK, and water retention is increased by LK knockdown only. Thus, the two colocalized peptides display similar systemic actions, but differ with respect to regulation of feeding and body water retention. We also demonstrated that DH44 and LK have additive effects on fluid secretion by MTs. It is likely that the colocalized peptides are coreleased from ABLKs into the circulation and act on the tubules where they target different cell types and signaling systems to regulate diuresis and stress tolerance. Additional targets seem to be specific for each of the two peptides and subserve regulation of feeding and water retention. Our data suggest that the ABLKs and hormonal actions are sufficient for many of the known DH44 and LK functions, and that the remaining neurons in the CNS play other functional roles.
Contrasting responses of phosphatase kinetic parameters to nitrogen and phosphorus additions in forest soils
Authors: Zhang Xinyu , Yang Yang , Zhang Chuang , Niu Shuli , Yang Hao , Yu Guirui , Wang Huimin , Blagodatskaya Evgenia , Kuzyakov Yakov , Tian Dashuan , Tang Yuqian , Liu Shuang , Sun Xiaomin
Published: July 2017

Global changes include increasing nitrogen (N) and phosphorus (P) deposition, which affect microbial nutrient demand and biogeochemical cycles. The responses of P‐mineralizing enzymes to these global change components are poorly defined and are not specified in forest soils differing in P content.

We chose one site in a P‐rich and two sites in P‐poor forests and established sixteen 20 × 20 m plots at each site. Control, either N only, P only, or combined N and P, were randomly distributed through each forest site with four replicates. We investigated the effects of N and P additions over 4 years on the phosphomonoesterase potential activity (Vmax), its half‐saturation constant (Km) and its catalytic efficiency (Vmax/Km).

Without N and P additions, the enzyme kinetic parameters Vmax, Km and Vmax/Km were higher in P‐rich than in P‐poor forest soils. These parameters increased with soil pH, SOC, TN and TP contents increased.

Remarkably, P additions caused the Vmax and Km to increase in P‐rich soils, but had no effect on Vmax/Km. P additions to P‐poor soils resulted in a decrease in the Vmax/Km via the inhibitory effects of inorganic P on the Vmax. N additions had no effect on the Vmax/Km in P‐rich and P‐poor soils because of the similar increases in the Vmax and Km. The effects of combined N and P and P only additions to P‐poor soils on the Vmax and Km were similar, but were stronger than the effects of N only or P only additions on the P‐rich soils.

Phosphatase kinetic parameters were positively related to the availability of N and P in P‐rich soils, but inorganic P inhibited phosphatase activity and caused a decrease in the catalytic efficiency in P‐poor soils. More microbial community groups could contribute to the secretion of a broader spectrum of iso‐enzymes under combined additions of N and P in P‐rich soils. We conclude contrast responses of phosphatase kinetics to P and N inputs in P‐rich and P‐poor forest soils, while long‐term N deposition might mitigate P limitation by increasing phosphatase secretion.

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Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid‐treated eosinophilic esophagitis
Authors: Simon D. , Page B. , Vogel M. , Bussmann C. , Blanchard C. , Straumann A. , Simon H.‐U.
Published: July 2017

Background

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen‐mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil‐predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in patients with EoE is owing to pre‐existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid (CS) therapy.

Methods

Medical histories, as well as serum and tissue samples of 60 patients with EoE (15 CS naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database (SEED) and Biobank, were analyzed. We applied ImmunoCAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components.

Results

Patients with EoE had higher total IgE levels and were more frequently sensitized to C. albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin (TSLP), cathelicidin, proteases, that is, the kallikreins (KLK)‐5 and KLK‐7, were observed as compared with controls, while reduced expression of lympho‐epithelial Kazal‐type‐related inhibitor (LEKTI), filaggrin, E‐cadherin, claudin, occludin, desmoglein‐1 was found, independent of CS therapy. In CS‐treated EoE, significantly lower numbers of CD1a+ cells and cathelicidin expression were noted as compared to CS‐naive EoE.

Conclusion

This study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote C. albicans colonization and likely subsequent sensitization.
Therapeutic effect of capsaicin nasal treatment in patients with mixed rhinitis unresponsive to intranasal steroids
Authors: Van Gerven L. , Steelant B. , Alpizar Y. A. , Talavera K. , Hellings P. W.
Published: July 2017

Literature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (J Allergy Clin Immunol. 2014;133:1332, J Allergy Clin Immunol. 2017; [Epub ahead of print]). “Mixed rhinitis” (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyper‐reactivity is a good predictor of positive outcome, and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients.
Lactobacillus reuteri DSM 17938 and a placebo both significantly reduced symptoms in children with functional abdominal pain
Authors: Maragkoudaki M , Chouliaras G , Orel R , Horvath A , Szajewska H , Papadopoulou A
Published: July 2017

Aim

Lactobacillus reuteri is a Gram‐positive bacterium that naturally inhabits the human intestinal tract. This study assessed how effectively the probiotic L. reuteri DSM 17938 managed childhood functional abdominal pain (FAP).

Methods

We recruited 54 children with a mean age 9.1 ± 3.8 years, who were diagnosed with FAP in the outpatient clinics of three university hospitals in Greece, Slovenia and Poland, according to the Rome III criteria, from January 2013 to December 2015. They were randomly assigned to receive either 2 × 108 colony‐forming units of L. reuteri (n = 27) or a placebo (n = 27) for four weeks.

Results

Both L. reuteri and the placebo significantly reduced the frequency and intensity of abdominal pain episodes at four and eight weeks compared to baseline (all p < 0.001). L. reuteri decreased the use of pain relieving drugs at four weeks and the number of child school and adult work absences at four and eight weeks, unlike the placebo, which achieved nonsignificant results. However, the difference between the groups did not reach significance. No side effects were recorded.

Conclusion

Both L. reuteri and the placebo were effective in alleviating pain in children with FAP, but only L. reuteri improved the child's and family's normal activities.
A longitudinal study of cognitive and educational outcomes of those born small for gestational age
Authors: Yu Bing , Garcy Anthony M.
Published: July 2017

Aim

This study examined the long‐term cognitive and educational outcomes of being born small for gestational age (SGA) and assessed whether the family's attitude towards education modified the effect of being born SGA on educational attainment.

Methods

We used anonymised data on 9598 individuals from the Stockholm Birth Cohort. This study focused on babies born in 1953 in the Stockholm metropolitan area, who were followed up for 50 years, and included educational data at the age of 13 and 48. Ordinary least squares regression analyses, modification analyses and logistic regression analyses were conducted.

Results

The findings suggested that individuals who were born SGA (n = 798) had lower mean verbal, spatial and numerical test scores than those born appropriate for gestational age (AGA) (n = 7364) and large for gestational age (n = 1436). The SGA/AGA differences were small, but statistically significant, and the effects of being born SGA on the test scores was modified by the family's attitude towards education. The findings also suggested that attaining higher education was largely, but not entirely, explained by the family's attitude towards education.

Conclusion

The detrimental effects of being born SGA were limited on cognitive and educational outcomes, but may have been reduced by positive family attitudes.
Long‐term outcomes and transmission rates in hepatitis C virus‐positive donor to hepatitis C virus‐negative kidney transplant recipients: Analysis of United States national data
Authors: Gupta Gaurav , Kang Le , Yu Jonathan W. , Limkemann Ashley J. , Garcia Victoria , Bandyopadhyay Dipankar , Kumar Dhiren , Fattah Hasan , Levy Marlon , Cotterell Adrian H. , Sharma Amit , Bhati Chandra , Reichman Trevor , King Anne L. , Sterling Richard
Published: July 2017

The use of kidneys from hepatitis C virus (HCV)‐positive (D+) deceased donors for HCV‐negative recipients (R−) might increase the donor pool. We analyzed the national Organ Procurement and Transplant Network (OPTN) registry from 1994 to 2014 to compare the outcomes of HCV D+/R− (n = 421) to propensity‐matched HCV‐negative donor (D−)/R− kidney transplants, as well as with waitlisted patients who never received a transplant, in a 1:5 ratio (n = 2105, per matched group). Both 5‐year graft survival (44% vs 66%; P < .001) and patient survival (57% vs 79%; P < .001) were inferior for D+/R− group compared to D−/R−. Nevertheless, 5‐year patient survival from the time of wait listing was superior for D+/R− when compared to waitlisted controls (68% vs 43%; P < .001). Of the 126 D+/R− with available post‐transplant HCV testing, HCV seroconversion was confirmed in 62 (49%), likely donor‐derived. Five‐year outcomes were similar between D+/R− that seroconverted vs D+/R− that did not (n = 64). Our analysis shows inferior outcomes for D+/R− patients although detailed data on pretransplant risk factors was not available. Limited data suggest that HCV transmission occurred in half of HCV D+/R− patients, although this might not have been the primary factor contributing to the poor observed outcomes.
Influence of kidney offer acceptance behavior on metrics of allocation efficiency
Authors: Wey Andrew , Salkowski Nicholas , Kasiske Bertram L. , Israni Ajay K. , Snyder Jon J.
Published: July 2017

We investigated associations of deceased donor kidney offer acceptance with likelihood of the kidney being discarded, cold ischemia time at transplant (CIT), and likelihood of the kidney being exported outside the donation service area (DSA). We used kidney offers from donors in the Scientific Registry of Transplant Recipients July 1, 2015‐June 30, 2016, and a stratified logistic regression to estimate odds ratios of acceptance for candidates wait‐listed in aDSA. We estimated associations between these ratios and likelihood of discard or export andCITat transplant. Approximately 0.50 kidneys were discarded per donor; lowerDSA‐specific offer acceptance ratios were associated with more discards (R=−0.20;P=0.006). For a median donor, theDSAwith the highest acceptance ratio would place 0.12 more kidneys per donor than theDSAwith the lowest ratio. Low acceptance ratios were associated with higherCIT(R=−0.23;P<0.001). For the median donor,CITwas 2.9 hours shorter for theDSAwith the highest versus lowest acceptance ratio. Low acceptance ratios were associated with more exports (R=−0.43;P<0.001); the probability was 15% higher for a median donor in theDSAwith the lowest versus highest acceptance ratio. Improving lower‐than‐expected offer acceptance would likely reduce discards,CIT, and exports.
Carrying capacity in a heterogeneous environment with habitat connectivity
Authors: Zhang Bo , Kula Alex , Mack Keenan M. L. , Zhai Lu , Ryce Arrix L. , Ni Wei‐Ming , DeAngelis Donald L. , Van Dyken J. David
Published: July 2017

A large body of theory predicts that populations diffusing in heterogeneous environments reach higher total size than if non‐diffusing, and, paradoxically, higher size than in a corresponding homogeneous environment. However, this theory and its assumptions have not been rigorously tested. Here, we extended previous theory to include exploitable resources, proving qualitatively novel results, which we tested experimentally using spatially diffusing laboratory populations of yeast. Consistent with previous theory, we predicted and experimentally observed that spatial diffusion increased total equilibrium population abundance in heterogeneous environments, with the effect size depending on the relationship between r and K. Refuting previous theory, however, we discovered that homogeneously distributed resources support higher total carrying capacity than heterogeneously distributed resources, even with species diffusion. Our results provide rigorous experimental tests of new and old theory, demonstrating how the traditional notion of carrying capacity is ambiguous for populations diffusing in spatially heterogeneous environments.
Climate warming: a loss of variation in populations can accompany reproductive shifts
Authors: Massot Manuel , Legendre Stéphane , Fédérici Pierre , Clobert Jean
Published: July 2017

The most documented response of organisms to climate warming is a change in the average timing of seasonal activities (phenology). Although we know that these average changes can differ among species and populations, we do not know whether climate warming impacts within‐population variation in phenology. Using data from five study sites collected during a 13‐year survey, we found that the increase in spring temperatures is associated with a reproductive advance of 10 days in natural populations of common lizards (Zootoca vivipara). Interestingly, we show a correlated loss of variation in reproductive dates within populations. As illustrated by a model, this shortening of the reproductive period can have significant negative effects on population dynamics. Consequently, we encourage tests in other species to assess the generality of decreased variation in phenological responses to climate change.
Factors controlling the stable isotope composition and C:N ratio of seston and periphyton in shallow lake mesocosms with contrasting nutrient loadings and temperatures
Authors: Trochine Carolina , Guerrieri Marcelo , Liboriussen Lone , Willems Priscila , Lauridsen Torben L. , Søndergaard Martin , Jeppesen Erik
Published: July 2017

Carbon (C) and nitrogen (N) stable isotope composition (15N:14N, δ15N and 13C:12C, δ13C) have been widely used to elucidate changes in aquatic ecosystem dynamics created by eutrophication and climate warming, often, however, without accounting for seasonal variation.

Here, we aim to determine the factors controlling the stable isotope composition and C:N ratio of seston and periphyton in shallow lakes with contrasting nutrient loadings and climate; for this purpose, we followed the monthly stable isotope composition (c. 1 year) of seston (SES) and periphyton (PER) in 24 mesocosms mimicking shallow lakes with two nutrient treatments (enriched and unenriched) and three temperature scenarios (ambient, +3 and +5°C).

Nutrient enrichment and warming had a stronger impact on the δ15N and δ13C values of seston than on periphyton, and the temporal isotopic variability in both communities was large.

δ15NPER did not differ markedly between nutrient treatments, whereas δ15NSES was lower in the enriched mesocosms, possibly reflecting higher N2‐fixation by cyanobacteria. δ15NSES was higher in winter in the heated mesocosms and its dynamics was linked with that of NH4‐N, whereas δ15NPER showed a stronger association with NO3‐N. δ15NSES demonstrated a positive relationship with mean monthly temperature, indicating less isotope fractionation among autotrophs when production increased.

δ13CSES was lowest in the enriched mesocosms during winter, whereas δ13CPER did not differ between nutrient treatments. δ13CSES and δ13CPER were positively related to pH, likely reflecting a pH‐induced differential access to dissolved carbon species in the primary producers. The positive δ13C‐temperature relationship suggested less fractionation of CO2 and HCO3− and/or larger use of HCO3− at higher temperatures.

The C:N ratios varied seasonally and the differences between the enriched and unenriched mesocosms were stronger for seston than for periphyton. Particularly, the C:NSES ratios did not indicate deficiencies in N as opposed to the C:NPER ratios, supporting the observed changes in δ15N and suggesting that seston and periphyton have access to different sources of nutrients. We did not observe any clear effect of temperature warming on the C:N ratios.

Our study provides evidence of strong seasonality in the isotopic composition and C:N ratios of seston and periphyton across nutrient and temperature levels; also, we identified several factors that are likely to modulate the strength and variability in stable isotopes values and stoichiometry of sestonic and periphytic communities under these scenarios.