bluuebunny/crossref_metadata_2025 huggingface dataset:
The shaping role of self-organization: linking vegetation patterning, plant traits and ecosystem functioning
Authors: Zhao Li-Xia , Xu Chi , Ge Zhen-Ming , van de Koppel Johan , Liu Quan-Xing
Published: April 2019

Self-organized spatial patterns are increasingly recognized for their contribution to ecosystem functioning, in terms of enhanced productivity, ecosystem stability, and species diversity in terrestrial as well as marine ecosystems. Most studies on the impact of spatial self-organization have focused on systems that exhibit regular patterns. However, there is an abundance of patterns in many ecosystems which are not strictly regular. Understanding of how these patterns are formed and how they affect ecosystem function is crucial for the broad acceptance of self-organization as a keystone process in ecological theory. Here, using transplantation experiments in salt marsh ecosystems dominated by
Scirpus mariqueter
, we demonstrate that scale-dependent feedback is driving irregular spatial pattern formation of vegetation. Field observations and experiments have revealed that this self-organization process affects a range of plant traits, including shoot-to-root ratio, rhizome orientation, rhizome node number, and rhizome length, and enhances vegetation productivity. Moreover, patchiness in self-organized salt marsh vegetation can support a better microhabitat for macrobenthos, promoting their total abundance and spatial heterogeneity of species richness. Our results extend existing concepts of self-organization and its effects on productivity and biodiversity to the spatial irregular patterns that are observed in many systems. Our work also helps to link between the so-far largely unconnected fields of self-organization theory and trait-based, functional ecology.
Polar gigantism and the oxygen–temperature hypothesis: a test of upper thermal limits to body size in Antarctic pycnogonids
Authors: Shishido Caitlin M. , Woods H. Arthur , Lane Steven J. , Toh Ming Wei A. , Tobalske Bret W. , Moran Amy L.
Published: April 2019

The extreme and constant cold of the Southern Ocean has led to many unusual features of the Antarctic fauna. One of these, polar gigantism, is thought to have arisen from a combination of cold-driven low metabolic rates and high oxygen availability in the polar oceans (the ‘oxygen–temperature hypothesis'). If the oxygen–temperature hypothesis indeed underlies polar gigantism, then polar giants may be particularly susceptible to warming temperatures. We tested the effects of temperature on performance using two genera of giant Antarctic sea spiders (Pycnogonida),
Colossendeis
and
Ammothea
, across a range of body sizes. We tested performance at four temperatures spanning ambient (−1.8°C) to 9°C. Individuals from both genera were highly sensitive to elevated temperature, but we found no evidence that large-bodied pycnogonids were more affected by elevated temperatures than small individuals; thus, these results do not support the predictions of the oxygen–temperature hypothesis. When we compared two species,
Colossendeis megalonyx
and
Ammothea glacialis
,
C. megalonyx
maintained performance at considerably higher temperatures. Analysis of the cuticle showed that as body size increases, porosity increases as well, especially in
C. megalonyx
, which may compensate for the increasing metabolic demand and longer diffusion distances of larger animals by facilitating diffusive oxygen supply.
Do traits separated by metamorphosis evolve independently? Concepts and methods
Authors: Collet Julie , Fellous Simon
Published: April 2019

Despite the ubiquity of complex life cycles, we know little of the evolutionary constraints exerted by metamorphosis. Here, we present pitfalls and methods to answer whether animals with a complex life cycle can independently adapt to the environments encountered at each life stage, with a specific focus on the microevolution of quantitative characters. We first discuss challenges associated with study traits and populations. We further emphasize the benefits of using a combination of approaches. We then develop how multivariate methods can limit several issues by revealing genetic patterns that are invisible when only considering trait-by-trait genetic correlations. Finally, we detail how Lande's work on sexual dimorphism can be applied in measuring G matrices across life stages. The methods and tools described here will contribute towards building a predictive framework for trait evolution across life stages.
Malachite: A Gene Enrichment Meta-Analysis (GEM) Tool for ToppGene
Authors: Gershkowitz Gregory R. , Abrams Zachary B. , Coombes Caitlin E. , Coombes Kevin R.
Published: April 2019

Background

Researchers commonly use online tools such as ToppGene to conduct enrichment analyses on gene expression data. This process does not easily allow multiple gene data sets to be analyzed and compared at once. ToppGene requires the user to manually enter gene symbols or other gene identifiers into a text box and to manually sift through forms with many adjustable parameters in order to obtain a downloadable text file of results. This process makes the analysis of multiple sets of genes tedious, time-consuming, and error prone. To address this problem, we developed Malachite, a Python package that enables researchers to perform gene enrichment analyses on multiple gene lists and concatenate the resulting enrichment statistics. In this way, Malachite enables meta-enrichment analyses across multiple data sets.

Results

To illustrate its use, we applied Malachite to three data sets from the Gene Expression Omnibus comparing gene expression in the large airways of smokers and non-smokers. Biological processes enriched in all three data sets were related to xenobiotic stimulus; molecular functions typically involved nicotinamide adenine dinucleotide phosphate (NADP) activity.

Conclusion

Malachite enables researchers to automate gene enrichment metaanalyses using ToppGene. Malachite also enhances ToppGene’s gene set analysis of drug-gene relationships by further filtering for FDA approved drugs.
Co-culture ofSaccharomyces cerevisiae(VS3) andPichia stipitis(NCIM 3498) for bioethanol production using concentratedProsopis julifloraacid hydrolysate
Authors: Naseeruddin Shaik , Desai Suseelendra , Rao L Venkateswar
Published: April 2019

Bioethanol production from lignocellulosic biomass is a viable option for improving energy security and reducing green house emissions. In the present studyProsopis juliflora, an invasive tree found through out India, with total carbohydrate content of 67.4 +/- 6% was selected as lignocellulosic feedstock for bioethanol production. The hydrolysate obtained after biphasic dilute acid hydrolysis contained initial sugar concentration of 18.70 +/- 0.16 g/L and hence to increase the ethanol yield it was concentrated to 33.59 +/- 0.52 g/L (about two-folds) by vacuum distillation. The concentration of sugars, phenols and furans was analyzed before and after concentration process. The concentrated hydrolysate was further detoxified by over liming, neutralization and charcoal treatment and later used for ethanol fermentation by mono- and co culture method. Monoculture ofSaccharomyces cerevisiae(VS3) andPichia stipitis(NCIM 3498) produced 8.52 +/- 0.43 and 4.52 +/- 0.23 g/L of ethanol with 66.21 +/- 3.26% and 60.46 +/- 3.02% of fermentation efficiency, 0.33 +/- 0.02 and 0.31 +/- 0.02 g/g of ethanol yield and 0.24 +/- 0.01 and 0.13 +/- 0.01 g/L/h of productivity, respectively. The co-culture ofS. cerevisiae(VS3) andP. stipitis(NCIM 3498) helped to improve all parameters i.e. 10.94 +/- 0.53 g/L of ethanol with fermentation efficiency, ethanol yield and productivity of 83.11 +/- 0.42%, 0.420 +/- 0.01 g/g and 0.30 +/- 0.01 g/L/h, respectively.
Proteome analysis of xylose metabolism inRhodotorula toruloidesduring lipid production
Authors: Tiukova Ievgeniia A. , Brandenburg Jule , Blomqvist Johanna , Samples Sabine , Mikkelsen Nils , Skaugen Morten , Øverlie Arntzen Magnus , Nielsen Jens , Sandgren Mats , Kerkhoven Eduard J.
Published: April 2019

Background

Rhodotorula toruloidesis a promising platform organism for production of lipids from lignocellulosic substrates. Little is known about the metabolic aspects of lipid production from the lignocellolosic sugar xylose by oleaginous yeasts in general andR. toruloidesin particular. This study presents the first proteome analysis of the metabolism ofR. toruloidesduring conversion of xylose to lipids.

Results

R. toruloidescultivated on either glucose or xylose was subjected to comparative analysis of its growth dynamics, lipid composition, fatty acid profiles and proteome. The maximum growth and sugar uptake rate of glucose-grownR. toruloidescells were almost twice that of xylose-grown cells. Cultivation on xylose medium resulted in a lower final biomass yield although final cellular lipid content was similar between glucose- and xylose-grown cells. Analysis of lipid classes revealed the presence of monoacylglycerol in the early exponential growth phase as well as a high proportion of free fatty acids. Carbon source-specific changes in lipid profiles were only observed at early exponential growth phase, where C18 fatty acids were more saturated in xylose-grown cells. Proteins involved in sugar transport, initial steps of xylose assimilation and NADPH regeneration were among the proteins whose levels increased the most in xylose-grown cells across all time points. The levels of enzymes involved in the mevalonate pathway, phospholipid biosynthesis and amino acids biosynthesis differed in response to carbon source. In addition, xylose-grown cells contained higher levels of enzymes involved in peroxisomal beta-oxidation and oxidative stress response compared to cells cultivated on glucose.

Conclusions

The results obtained in the present study suggest that sugar import is the limiting step during xylose conversion byR. toruloidesinto lipids. NADPH appeared to be regenerated primarily through pentose phosphate pathway although it may also involve malic enzyme as well as alcohol and aldehyde dehydrogenases. Increases in enzyme levels of both fatty acid biosynthesis and beta-oxidation in xylose-grown cells was predicted to result in a futile cycle. The results presented here are valuable for the development of lipid production processes employingR. toruloideson xylose-containing substrates.
Ancestral role of Fat-like cadherins in planar cell polarity
Authors: Brooun Maria , Klimovich Alexander , Bashkurov Mikhail , Pearson Bret J. , Steele Robert E. , McNeill Helen
Published: April 2019

Fat family cadherins are enormous proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterian animals. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins inHydra, a member of the early-diverging metazoan phylum Cnidaria.Hydrahas a simple body plan with only two epithelial layers and radial symmetry. We find thatHydrahomologues of Fat-like (HyFat) and Dachsous (HyDs) co-localize at the apico-lateral membrane of ectodermal epithelial cells. Remarkably, HyFat is planar polarized perpendicular to the oral-aboral axis of the animal. Using knockdown approaches we found that HyFat is involved in the regulation of local cell alignment, but is dispensable for the global alignment of ectodermal myonemes along the oral-aboral axis. The intracellular domain (ICD) of HyFat is involved in the morphogenesis of ectodermal myonemes. Thus, Fat family cadherins have ancient, prebilaterian functions in cell adhesion, tissue organization and planar polarity.
Zinc Solubilizing Plant Growth Promoting Microbes Produce Zinc Nanoparticles
Authors: Sultana Uzma , Desai Suseelendra , Reddy Gopal , Prasad TNVKV
Published: April 2019

Strains of Pseudomonas, Bacillus and Azospirillum with plant growth promoting ability were checked for their zinc solubilizing ability. Efficient zinc solubilizers were checked for their ability to produce nano-scale zinc particles. The nanoparticles from the cell-free culture filtrates obtained from these strains were characterized for particle size, Zeta potential and functional groups. Presence of Zn nanoparticles in the bacterial culture filtrate was confirmed by particle distribution and Scanning electron microscope (SEM) analysis. Most properties of nanoparticles are size dependent. Zinc nanoparticles were observed to be spherical in shape and size ranged from 52.0 to 106.0 nm. Zeta potential of the Zn nanoparticles was estimated to understand the stability of the particles. The measured zeta potentials varied from −14.5mV to +179.10 mV indicating high stability and dispersion of the zinc nanoparticles. FTIR peaks at different wave numbers depicted the role of functional groups of proteins in the biosynthesis of Zn nanoparticles. This finding opens a new area of research focusing on microbe-microbe interactions in rhizosphere and plant-microbe interactions at rhizosphere apart from biosynthesis of nanoparticles, which has major applications. To our knowledge, this is the first report of production of nanoparticles as part of nutrient mobilization by plant growth promoting rhizobacteria.
Development of specific molecular markers to distinguish and quantify broomrape species in a soil sample from infected field
Authors: Aly Radi , Bari Vinay K. , Londner Avishai , Nassar Jackline Abu , Taha-Salaime Leena , Hanan Eizenberg , Lati Ran
Published: April 2019

Broomrapes (OrobancheandPhelipanche) are obligate holoparasites that cause heavy damage to numerous crops, reducing the yield and its quality. The parasite develops in the soil and exerts the greatest damage prior to its emergence; therefore the majority of field loss may occur before diagnosis of infection. Because of the parasite tiny seed size (200 to 300 μm) and dormancy for several decades in the field, it is very difficult to diagnose the parasite by conventional methods. Therefore, to restrict the parasite seeds spread and contamination to other commercial fields, development of DNA-based molecular markers to identify and quantify broomrape species in a soil sample is much needed. In this study, we developed a specific molecular marker (RbcL-M) based onrbcL(large subunit of the ribulose-bisphosphate carboxylase) gene fromOrobanche crenatato differentiate betweenOrobanche crenataandOrobanche cumana.Likewise, a specific marker (ITS100) based upon unique sequences in the internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA ofPhelipanche aegyptiacato quantify three species of the parasite (P. aegyptiaca, O. crenataandO. cumana) in a soil sample was developed. Genomic DNA was extracted from soil samples artificially infested with broomrape seeds or tissue ofP. aegyptiaca, O. cumanaandO. crenataand subjected to PCR analysis. RbcL-M marker successfully amplified a PCR product (1300bp) whenO. crenataseeds or tissues (collected from several locations in Israel) were added to the soil samples. The same marker amplified a PCR product (1000bp) whenO. cumanaseeds or tissues were added to the soil samples. RbcL-M marker did not amplify soil samples with seeds or tissues ofP. aegyptiacaor any soil-borne DNA. Furthermore, using ITS-100 marker and Real-Time PCR analysis, allowed quantitative diagnostic of the parasite in a soil sample from infected sunflower field. As expected the universal internal control primer (UCP-555) amplified a PCR product (555bp) when genomic DNA extracted from soil samples with or without broomrape tissues. The development of an efficient, simple and robust molecular marker to detect and distinguish between broomrape species, has a significant insights on assessment the level of infestation and planning eradication program to the parasite in a field crop.
Differential nanoscale organisation of LFA-1 modulates T cell migration
Authors: Shannon Michael J. , Pineau Judith , Griffié Juliette , Aaron Jesse , Peel Tamlyn , Williamson David J. , Zamoyska Rose , Cope Andrew P. , Cornish Georgina H. , Owen Dylan M.
Published: April 2019

Effector T-cells rely on integrins to drive adhesion and migration to facilitate their immune function. Heterodimeric transmembrane integrin LFA-1 (αLβ2) regulates adhesion and migration through linkage of the extracellular matrix with the intracellular actin treadmill machinery. We quantitated the velocity and direction of F-actin flow in migrating T-cells alongside single molecule localisation of transmembrane and intracellular LFA-1. Our results show that retrograde actin flow positively correlated and immobile actin negatively correlated with T-cell velocity. Plasma membrane localised LFA-1 forms unique nano-clustering patterns in the leading edge, compared to the mid-focal zone, in migrating T-cells. Deleting the cytosolic phosphatase PTPN22, a negative regulator of integrin signaling, increased T-cell velocity, and leading-edge cluster co-localisation of pY397 FAK, pY416 Src family kinases and LFA-1. These data suggest that differential nanoclustering patterns of LFA-1 in migrating T-cells can instruct intracellular signalling linked with the actin treadmill. Our data presents a paradigm where T cells modulate the nanoscale organisation of adhesion and signalling molecules to fine tune their migration speed. This has implications for the regulation of immune and inflammatory responses.
Potential of on-scalp MEG: Robust detection of human visual gamma-band responses
Authors: Iivanainen Joonas , Zetter Rasmus , Parkkonen Lauri
Published: April 2019

Electrophysiological signals recorded intracranially show rich frequency content spanning from near-DC to hundreds of hertz. Noninvasive electromagnetic signals measured with electroencephalography (EEG) or magnetoencephalography (MEG) typically contain less signal power in high frequencies than invasive recordings. Particularly, noninvasive detection of gamma-band activity (> 30 Hz) is challenging since coherently active source areas are small at such frequencies and the available imaging methods have limited spatial resolution. Compared to EEG and conventional SQUID-based MEG, on-scalp MEG should provide substantially improved spatial resolution, making it an attractive method for detecting gamma-band activity.

Using an on-scalp array comprised of eight optically-pumped magnetometers (OPMs) and a conventional whole-head SQUID array, we measured responses to a dynamic visual stimulus known to elicit strong gamma-band responses. OPMs had substantially higher signal power than SQUIDs, and had a slightly larger relative gamma-power increase over the baseline. With only eight OPMs, we could obtain gamma-activity source estimates comparable to those of SQUIDs at the group level.

Our results show the feasibility of OPMs to measure gamma-band activity. To further facilitate the noninvasive detection of gamma-band activity, the on-scalp OPM arrays should be optimized with respect to sensor noise, the number of sensors and inter-sensor spacing.
Temporal processing of facial expressions of mental states
Authors: Schmidtmann Gunnar , Loong Joshua T. , Carbon Claus-Christian , Jordan Maiya , Logan Andrew J. , Gold Ian
Published: April 2019

Faces provide not only cues to an individual’s identity, age, gender and ethnicity, but also insight into their mental states. The ability to identify the mental states of others is known as Theory of Mind. Here we present results from a study aimed at extending our understanding of differences in the temporal dynamics of the recognition of expressions beyond the basic emotions at short presentation times ranging from 12.5 to 100 ms. We measured the effect of variations in presentation time on identification accuracy for 36 different facial expressions of mental states based on the Reading the Mind in the Eyes test (Baron-Cohen et al., 2001) and compared these results to those for corresponding stimuli from the McGill Face database, a new set of images depicting mental states portrayed by professional actors. Our results show that subjects are able to identify facial expressions of complex mental states at very brief presentation times. The kind of cognition involved in the correct identification of facial expressions of complex mental states at very short presentation times suggests a fast, automatic Type-1 cognition.
WASP restricts active Rac to maintain cells’ front-rear polarisation
Authors: Amato Clelia , Thomason Peter , Davidson Andrew , Swaminathan Karthic , Ismail Shehab , Machesky Laura , Insall Robert
Published: April 2019

Efficient motility requires polarised cells, with anterior pseudopods and a retracting rear. This polarisation requires that the pseudopod catalyst Rac is restricted to the front. Here we show that the Arp2/3 complex regulator WASP is important for maintaining front–rear polarity, using a mechanism that limits where active Rac localises. Dictyostelium cells lacking WASP inappropriately activate Rac and SCAR/WAVE at their rears, leading to reduced cell speed. WASP facilitates the internalisation of clathrin-coated pits, and its Rac-binding CRIB motif is considered essential for its localisation and activity. However, WASP mutants with deleted CRIB domains, or harbouring a new mutation that prevents Rac binding, localise normally, recruit Arp2/3 complex, and drive actin polymerisation. Similarly, Rac inhibitors do not block WASP localisation or activation. Despite this, WASP CRIB mutants cannot restore polarisation of active Rac. Thus, WASP’s interaction with Rac regulates Rac activity and cell polarity, but is dispensable for activating actin polymerization.
MuGVRE. A virtual research environment for 3D/4D genomics
Authors: Codó Laia , Bayarri Genís , Cid-Fuentes Javier Alvarez , Conejero Javier ,   Adam Hospital, Royo Romina , Repchevsky Dmitry , Pasi Marco , Meletiou Athina , McDowall Mark D. , Reham Fatima , Alcantara José A. , Jimenez-Garcia Brian , Walther Jürgen , Illa Ricard , Serra François , Goodstadt Michael , Castillo David , Sati Satish , Buitrago Diana , Brun-Heath Isabelle , Fernandez-Recio Juan , Cavalli Giacomo , Marti-Renom Marc , Yates Andrew , Laughton Charles A. , Badia Rosa M. , Orozco Modesto , Gelpí Josep Ll.
Published: April 2019

Multiscale Genomics (MuG) Virtual Research Environment (MuGVRE) is a cloud-based computational infrastructure created to support the deployment of software tools addressing the various levels of analysis in 3D/4D genomics. Integrated tools tackle needs ranging from high computationally demanding applications (e.g. molecular dynamics simulations) to high-throughput data analysis applications (like the processing of next generation sequencing). The MuG Infrastructure is based on openNebula cloud systems implemented at the Institute for research in Biomedicine, and the Barcelona Supercomputing Center, and has specific interfaces for users and developers. Interoperability of the tools included in MuGVRE is maintained through a rich set of metadata allowing the system to associate tools and data in a transparent manner. Execution scheduling is based in a traditional queueing system to handle demand peaks in applications of fixed needs, and an elastic and multi-scale programming model (pyCOMPSs, controlled by the PMES scheduler), for complex workflows requiring distributed or multi-scale executions schemes. MuGVRE is available athttps://vre.multiscalegenomics.euand documentation and general information athttps://www.multiscalegenomics.eu. The infrastructure is open and freely accessible.
Intrinsic sensory disinhibition contributes to intrusive re-experiencing in combat veterans
Authors: Clancy Kevin J. , Albizu Alejandro , Schmidt Norman B. , Li Wen
Published: April 2019

Intrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder (PTSD). In contrast to abstract, verbal intrusions in other affective disorders, intrusive re-experiencing in PTSD is characterized by vivid sensory details as “flashbacks”. While prevailing PTSD models largely focus on dysregulated emotional processes, we hypothesize that deficient sensory inhibition in PTSD could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions of trauma. In 86 combat veterans, we examined resting-state alpha (8-12 Hz) oscillatory activity (in both power and posterior→frontal connectivity), given its key role in sensory cortical inhibition, in association with intrusive re-experiencing symptoms. A subset (N = 35) of veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed a strong association between intrusive re-experiencing symptoms and attenuated resting-state posterior→frontal alpha connectivity, which were both correlated with olfactory trauma memory (but not emotional response). Importantly, olfactory trauma memory was further identified as a full mediator of the relationship between alpha connectivity and intrusive re-experiencing in these veterans, suggesting that deficits in intrinsic sensory inhibition can contribute to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and spontaneously activating sensory representations of trauma, impaired sensory inhibition can constitute a sensory mechanism of intrusive re-experiencing in PTSD.

HIGHLIGHTS

Alpha oscillations (indexing sensory inhibition) measured in 86 combat veterans

Re-experiencing symptom severity was associated with attenuated alpha connectivity

Trauma memory for, not emotional response to, odors mediated this relationship

Trauma memories may arise via disinhibited activation of sensory representations

Sensory systems may be novel target for intrusive re-experiencing symptom treatment
Increased nitrogen fixation and remobilization may contribute to higher seed protein without a yield penalty in a soybean introgression line
Authors: Locke Anna M. , Ramirez Martha E.
Published: April 2019

The development of soybean varieties with higher seed protein concentration has been hindered by a negative correlation between seed protein concentration and yield. Benning HP, a genotype that breaks this tradeoff, contains a high protein allele introgressed into the cultivar Benning. Because seed protein is thought to be limited by N, field and growth chamber experiments were performed to identify the N flux(es) that enable Benning HP’s increased seed protein without a yield penalty. When the N source was completely controlled in growth chambers, Benning HP was able to fix more N than its recurrent parent, but this response depended on the strain of the rhizobia symbiont and was not observed at all developmental stages. In the field, Benning HP remobilized N from its leaves at a higher rate during seed fill, but this response was only observed in one of the years studied. These results demonstrate that Benning HP has higher potential for N fixation and N remobilization from vegetative tissue compared to its lower protein recurrent parent, but those traits are not consistently expressed and may depend on environmental and sink control.
Home, head direction stability and grid cell distortion
Authors: Sanguinetti-Scheck Juan Ignacio , Brecht Michael
Published: April 2019

The home is a unique location in the life of humans and animals. Numerous behavioral studies investigating homing indicate that many animals maintain an online representation of the direction of the home, a home vector. Here we placed the rat’s home cage in the arena, while recording neurons in the animal’s parasubiculum and medial entorhinal cortex. From a pellet hoarding paradigm it became evident that the home cage induced locomotion patterns characteristic of homing behaviors. We did not observe home-vector cells. We found that head-direction signals were unaffected by home location. However, grid cells were distorted in the presence of the home cage. While they did not globally remap, single firing fields were translocated towards the home. These effects appeared to be geometrical in nature rather than a home-specific distortion. Our work suggests that medial entorhinal cortex and parasubiculum do not contain an explicit neural representation of the home direction.
Multi-disease associated risk locus inIL6represses the anti-inflammatory geneGPNMBthrough chromatin looping and recruiting MEF2-HDAC complex
Authors: Kong Xiufang , Sawalha Amr H
Published: April 2019

We have previously revealed a genetic association between Takayasu arteritis and a non-coding genetic variant in an enhancer region withinIL6(rs2069837 A/G). The risk allele in this variant (allele A) has a protective effect against chronic viral infection and cancer. Using a combination of experimental and bioinformatics tools, we identified the monocyte/macrophage anti-inflammatory geneGPNMB, ∼520kb away, as a target gene regulated by rs2069837. We revealed preferential recruitment of myocyte enhancer factor 2-histone deacetylase (MEF2-HDAC) repressive complex to the Takayasu arteritis risk allele. Further, we demonstrated suppression of GPNMB expression in monocyte-derived macrophages from healthy individuals with the AA compared to AG genotype, which was reversed by histone deacetylase inhibition. Our data suggest that the A allele in rs2069837 represses the expression of GPNMB by recruiting MEF2-HDAC complex, enabled through a long-range intra-chromatin looping mediated by CTCF. Suppression of this anti-inflammatory gene might mediate increased susceptibility in Takayasu arteritis and enhance protective immune responses in chronic infection and cancer. Our data highlight long-range chromatin interactions in functional genomic studies.
Towards HCP-Style Macaque Connectomes: 24-Channel 3T Multi-Array Coil, MRI Sequences and Preprocessing
Authors: Autio Joonas A. , Glasser Matthew F. , Ose Takayuki , Donahue Chad J. , Bastiani Matteo , Ohno Masahiro , Kawabata Yoshihiko , Urushibata Yuta , Murata Katsutoshi , Nishigori Kantaro , Yamaguchi Masataka , Hori Yuki , Yoshida Atsushi , Go Yasuhiro , Coalson Timothy S. , Jbabdi Saad , Sotiropoulos Stamatios N. , Smith Stephen , Van Essen David C. , Hayashi Takuya
Published: April 2019

Macaque monkeys are an important model species for understanding cortical organization of primates, yet tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the relatively thin macaque cortex, high spatial, temporal, and angular resolutions are required while maintaining high signal-to-noise ratio to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enabled adaptation of the Human Connectome Project (HCP) image acquisition protocols to the macaque brain. We also adapted HCP preprocessing methods optimized for the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provided high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold acceleration for dMRI and fMRI, respectively. Automated parcellation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available for humans.

Highlights

➢

24-channel 3T MR receive coil designed for the smaller macaque brain.

➢

In vivo macaque imaging protocols adapted according to guidelines from the HCP.

➢

Parallel imaging yields five- and four-fold acceleration in fMRI and dMRI sampling.

➢

HCP’s minimal preprocessing and denoising pipelines adapted for macaques.

➢

The multi-modal MRI data show considerable promise for HCP-style analyses.
Pigeon foot feathering reveals conserved limb identity networks
Authors: Boer Elena F. , Van Hollebeke Hannah F. , Park Sungdae , Infante Carlos R. , Menke Douglas B. , Shapiro Michael D.
Published: April 2019

The tetrapod limb is a stunning example of evolutionary diversity, with dramatic variation not only among distantly related species, but also between the serially homologous forelimbs (FLs) and hindlimbs (HLs) within species. Despite this variation, highly conserved genetic and developmental programs underlie limb development and identity in all tetrapods, raising the question of how limb diversification is generated from a conserved toolkit. In some breeds of domestic pigeon, shifts in the expression of two conserved limb identity transcription factors,PITX1andTBX5, are associated with the formation of feathered HLs with partial FL identity. To determine how modulation ofPITX1andTBX5expression affects downstream gene expression, we compared the transcriptomes of embryonic limb buds from pigeons with scaled and feathered HLs. We identified a set of differentially expressed genes enriched for genes encoding transcription factors, extracellular matrix proteins, and components of developmental signaling pathways with important roles in limb development. A subset of the genes that distinguish scaled and feathered HLs are also differentially expressed between FL and scaled HL buds in pigeons, pinpointing a set of gene expression changes downstream ofPITX1andTBX5in the partial transformation from HL to FL identity. We extended our analyses by comparing pigeon limb bud transcriptomes to chicken, anole lizard, and mammalian datasets to identify deeply conservedPITX1- andTBX5-regulated components of the limb identity program. Our analyses reveal a suite of predominantly low-level gene expression changes that are conserved across amniotes to regulate the identity of morphologically distinct limbs.

Summary statement

In feather-footed pigeons, mutant alleles ofPITX1andTBX5drive the partial redeployment of an evolutionarily conserved forelimb genetic program in the hindlimb.
Flexible neural connectivity under constraints on total connection strength
Authors: Ocker Gabriel Koch , Buice Michael A.
Published: April 2019

Neural computation is determined by neuron dynamics and circuit connectivity. Uncertain and dynamic environments may require neural hardware to adapt to different computational tasks, each requiring different connectivity configurations. At the same time, connectivity is subject to a variety of constraints, placing limits on the possible computations a given neural circuit can perform. Here we examine the hypothesis that the organization of neural circuitry favors computational flexibility: that it makes many computational solutions available, given physiological constraints. From this hypothesis, we develop models of the degree distributions of connectivity based on constraints on a neuron’s total synaptic weight. To test these models, we examine reconstructions of the mushroom bodies from the first instar larva and the adult Drosophila melanogaster. We perform a Bayesian model comparison for two constraint models and a random wiring null model. Overall, we find that flexibility under a homeostatically fixed total synaptic weight describes Kenyon cell connectivity better than other models, suggesting a principle shaping the apparently random structure of Kenyon cell wiring. Furthermore, we find evidence that larval Kenyon cells are more flexible earlier in development, suggesting a mechanism whereby neural circuits begin as flexible systems that develop into specialized computational circuits.

Author summary

High-throughput electron microscopic anatomical experiments have begun to yield detailed maps of neural circuit connectivity. Uncovering the principles that govern these circuit structures is a major challenge for systems neuroscience. Healthy neural circuits must be able to perform computational tasks while satisfying physiological constraints. Those constraints can restrict a neuron’s possible connectivity, and thus potentially restrict its computation. Here we examine simple models of constraints on total synaptic weights, and calculate the number of circuit configurations they allow: their computational flexibility. We propose probabilistic models of connectivity that weight the number of synaptic partners according to computational flexibility under a constraint and test them using recent wiring diagrams from a learning center, the mushroom body, in the fly brain. We compare constraints that fix or bound a neuron’s total connection strength to a simple random wiring null model. Of these models, the fixed total connection strength matched the overall connectivity best in mushroom bodies from both larval and adult flies. We also provide evidence suggesting that neural circuits are more flexible in early stages of development and lose this flexibility as they grow towards specialized function.
WRKY1 mediates transcriptional crosstalk between light and nitrogen signaling pathways in Arabidopsis thaliana
Authors: Heerah Sachin , Katari Manpreet , Penjor Rebecca , Coruzzi Gloria , Marshall-Colon Amy
Published: April 2019

Plant responses to multiple stimuli must be integrated to trigger transcriptional cascades that lead to changes in plant metabolism and development. Light (L) and nitrogen (N) are two signaling pathways that are intimately connected to each other and to plant energy status. Here, we describe the functional role of the WRKY1 transcription factor in mediating the regulation between L and N signaling pathways in Arabidopsis thaliana. WRKY1 participates in genome-wide transcriptional reprogramming in leaves in response to individual and combined L and N signals. A regulatory network was identified, consisting of 724 genes regulated by WRKY1 and involved in both N and L signaling pathways. The loss of WRKY1 gene function has marked effects on the L and N response of genes involved in N uptake and assimilation (primary metabolism) as well as stress response pathways (secondary metabolism). Our results support a model in which WRKY1 enables plants to activate genes involved in the recycling of cellular carbon resources when L is limiting but N is abundant, and up-regulate amino acid metabolism genes when both L and N are limiting. In this potential energy conservation mechanism, WRKY1 integrates responses to N and light-energy status to trigger changes in plant metabolism.

Based on transcriptome analysis, the WRKY1 transcription factor mediates regulation of nitrogen and light signaling pathways in a potential energy conservation mechanism.
Comparative genomic analysis reveals a monophyletic cold adapted Arthrobacter cluster from polar and alpine regions
Authors: Shen Liang , Liu Yongqin , Xu Baiqing , Wang Ninglian , Anslan Sten , Ren Ping , Liu Fei , Zhou Yuguang , Liu Qing
Published: April 2019

Decrease in the frequency of arginine and increase in lysine are the trends that have been identified in the genomes of cold adapted bacteria. However, some cold adapted taxa show only limited or no detectable changes in the frequencies of amino acid composition. Here, we examined Arthrobacter spp. genomes from a wide range of environments on whether the genomic adaptations can be conclusively identified across genomes of taxa from polar and alpine regions. Phylogenetic analysis with a concatenated alignment of 119 orthologous proteins revealed a monophyletic clustering of seven polar and alpine isolated strains. Significant changes in amino acid composition related to cold adaptation were exclusive to seven of the twenty-nine strains from polar and alpine regions. Analysis of significant indicator genes and cold shock genes also revealed that clear differences could only be detected in the same seven strains. These unique characteristics may result from a vast exchange of genome content at the node leading to the monophyletic cold adapted Arthrobacter cluster predicted by the birth-and-death model. We then experimentally validated that strains with significant changes in amino acid composition have a better capacity to grow at low temperature than the mesophilic strains.

Importance

Acquisition of novel traits through horizontal gene transfer at the early divergence of the monophyletic cluster may accelerate their adaptation to low temperature. Our study reached a clear relationship between adaptation to cold and genomic features and would advanced in understanding the ambiguous results produced by the previous studies on genomic adaption to cold temperature.
Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection
Authors: van Hoek Monique L. , Kaushal Akanksha , Bishop Barney M. , Barksdale Stephanie M.
Published: April 2019

Our long-term goal is to identify new antimicrobial peptides that might be effective against pneumonicFrancisellainfection in mice. Previously, our group searched the peptidome of the American alligator for novel cationic antimicrobial peptides and identified a naturally-occurring C-terminal fragment of apolipoprotein C-1, which we called Apo6. This peptide was found to have antibacterial activity against the ESKAPE pathogens, including those exhibiting multi-drug resistance. In this work, we tested Apo6 and synthetic derivatives for antibacterial activity againstFrancisella tularensisincluding the virulent strainF. tularensisSchuS4.Francisellais inherently highly resistant to the cyclic peptide polymyxin antibiotics and beta-lactam antibiotics. We found that our synthetic peptide derivatives (called GATR peptides), designed with increased hydrophobicity and charge, had generally strongerin vitroantimicrobial activity againstFrancisellathan the parent peptide Apo6. The GATR peptides had a greater effect on the bacterial membrane than the Apo6 peptide and were able to bindFrancisellaLPS, suggesting their mechanism of action againstFrancisella. Cytotoxicity experiments showed low cytotoxicity for most of the GATR peptides, and whole organism toxicity studies in the waxworm allowed us to down-select to two our lead peptides, GATR-3 and GATR-6. These peptides were tested in a murine pulmonary tularemia model. We found that the GATR-3 peptide rescued 50-60% of mice from lethal tularemia infection when administered systemically through the intraperitoneal route. This peptide is a candidate for further pre-clinical studies for a potential peptide-based approach to tularemia.
Putative cis-regulatory elements predict iron deficiency responses in Arabidopsis roots
Authors: Schwarz Birte , Azodi Christina B. , Shiu Shin-Han , Bauer Petra
Published: April 2019

Iron (Fe) is a key cofactor in many cellular redox processes, including respiration and photosynthesis. Plant Fe deficiency (-Fe) activates a complex regulatory network which coordinates root Fe uptake and distribution to sink tissues, while avoiding over-accumulation of Fe and other metals to toxic levels. In Arabidopsis (Arabidopsis thaliana), FIT (FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR), a bHLH transcription factor (TF), is required for up-regulation of root Fe acquisition genes. However, other root and shoot -Fe-induced genes involved in Fe allocation and signaling are FIT-independent. The cis-regulatory code, i.e. the cis-regulatory elements (CREs) and their combinations that regulate plant -Fe-responses, remains largely elusive. Using Arabidopsis genome and transcriptome data, we identified over 100 putative CREs (pCREs) that were predictive of -Fe-induced up-regulation of genes in root tissue. We used large-scale in vitro TF binding data, association with FIT-dependent or FIT-independent co-expression clusters, positional bias, and evolutionary conservation to assess pCRE properties and possible functions. In addition to bHLH and MYB TFs, also B3, NAC, bZIP, and TCP TFs might be important regulators for -Fe responses. Our approach uncovered IDE1 (Iron Deficiency-responsive Element 1), a -Fe response CRE in grass species, to be conserved in regulating genes for biosynthesis of Fe-chelating compounds also in Arabidopsis. Our findings provide a comprehensive source of cis-regulatory information for -Fe-responsive genes, that advances our mechanistic understanding and informs future efforts in engineering plants with more efficient Fe uptake or transport systems.

One sentence summary

>100 putative cis-regulatory elements robustly predict Arabidopsis root Fe deficiency-responses in computational models, and shed light on the mechanisms of transcriptional regulation.
Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells
Authors: Ross Ewan A , Turner Lesley-Anne , Saeed Anwar , Burgess Karl V , Blackburn Gavin , Reynolds Paul , Wells Julia A , Mountford Joanne , Gadegaard Nikolaj , Salmeron-Sanchez Manuel , Oreffo Richard OC , Dalby Matthew J
Published: April 2019

Mesenchymal stem cells (MSCs) are multipotent stem cells that are immunosuppressive and thus of considerable therapeutic potential in transplant operations. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunosuppressive therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can modulate paracrine activities of MSCs. Here, we show for the first time that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension increasing oxidative glycolysis. We also use the nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture. Our findings show a novel route to support large-scale expansion of functional MSCs for therapeutic purposes
AGO1x prevents dsRNA-induced interferon signaling to promote breast cancer cell proliferation
Authors: Ghosh Souvik , Guimaraes Joao C , Lanzafame Manuela , Schmidt Alexander , Syed Afzal Pasha , Dimitriades Beatrice , Börsch Anastasiya , Ghosh Shreemoyee , Correia Ana Luisa , Danner Johannes , Meister Gunter , Terracciano Luigi M. , Piscuoglio Salvatore , Zavolan Mihaela
Published: April 2019

Initially reported for viral RNA, elongation of polypeptide chains beyond the stop codon (translational readthrough (TR)) also occurs on eukaryotic transcripts. TR diversifies the proteome and can modulate protein levels 1-6. Here we report that AGO1x, a conserved TR isoform of Argonaute 1, is generated in highly proliferative breast cancer cells, where it curbs accumulation of double stranded RNAs, the induction of the interferon response and apoptosis. In contrast to other mammalian Argonaute protein family members with primarily cytoplasmic functions, AGO1x localizes to the nucleus, in the vicinity of nucleoli. We identify a novel interaction of AGO1x with the Polyribonucleotide Nucleotidyltransferase 1, depletion of either protein leading to dsRNA accumulation and impaired cell proliferation. Our study thus uncovers a novel function of an Argonaute protein outside of the miRNA effector pathway, in buffering dsRNA-induced interferon responses. As AGO1x expression is tightly linked to breast cancer cell proliferation, our study suggests a new direction for limiting tumor growth.