bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of cytochrome P450 1232A24 and 1232F1 from Arthrobacter sp. and their role in the metabolic pathway of papaverine
Authors: Klenk Jan M , Fischer Max-Philipp , Dubiel Paulina , Sharma Mahima , Rowlinson Benjamin , Grogan Gideon , Hauer Bernhard
Published: February 2019

Cytochrome P450 monooxygenases (P450s) play crucial roles in the cell metabolism and provide an unsurpassed diversity of catalysed reactions. Here, we report the identification and biochemical characterization of two P450s from Arthrobacter sp., a Gram-positive organism known to degrade the opium alkaloid papaverine. Combining phylogenetic and genomic analysis suggested physiological roles for P450s in metabolism and revealed potential gene clusters with redox partners facilitating the reconstitution of the P450 activities in vitro. CYP1232F1 catalyses the para demethylation of 3,4-dimethoxyphenylacetic acid to homovanillic acid while CYP1232A24 continues demethylation to 3,4-dihydroxyphenylacetic acid. Interestingly, the latter enzyme is also able to perform both demethylation steps with preference for the meta position. The crystal structure of CYP1232A24, which shares only 29% identity to previous published structures of P450s helped to rationalize the preferred demethylation specificity for the meta position and also the broader substrate specificity profile. In addition to the detailed characterization of the two P450s using their physiological redox partners, we report the construction of a highly active whole-cell Escherichia coli biocatalyst expressing CYP1232A24, which formed up to 1.77 g l−1 3,4-dihydroxyphenylacetic acid. Our results revealed the P450s’ role in the metabolic pathway of papaverine enabling further investigation and application of these biocatalysts.
Leo Sachs. 14 October 1924—12 December 2013
Authors: Groner Yoram , Sachs Pnina , Lotem Joseph
Published: February 2019

Leo Sachs was a worldwide renowned scientist for his major contributions in several fields. In the mid 1950s he showed that amniocentesis could be used for prenatal diagnosis of sex and blood group antigens. He then focused on various aspects of normal development and cancer, including the control of normal haematopoiesis and leukaemia, carcinogenesis
in vitro
by polyoma and SV40 tumour viruses, chemical carcinogens and X-rays, chromosomes and the reversibility of cancer, surface membrane changes in malignant cells and suppression of malignancy by inducing differentiation. The cell culture system he established in the early 1960s for the clonal development of normal haematopoietic cells made it possible to analyse the molecular basis of normal haematopoiesis, and discover the proteins that regulate viability, proliferation and differentiation of different blood cell lineages and the changes that drive leukaemia. His studies established significant general concepts, including: the differential responsiveness of cancer cells to normal regulators of development; suppression of myeloid leukaemia by inducing differentiation, bypassing malignancy-driving genetic defects; identification of chromosomes that control tumour suppression; discovering apoptosis as a major mechanism by which WT-p53 suppresses malignancy; and the ability of haematopoietic cytokines to suppress apoptosis in both normal and leukaemic cells. Leo was fortunate to witness his pioneering discoveries and ideas move from the basic science stage to effective clinical applications, using amniocentesis for prenatal detection of genetic abnormalities, augmenting normal haematopoiesis in patients with various haematopoietic deficiencies and suppressing malignancy by inducing differentiation and apoptosis.
Eunice Foote, John Tyndall and a question of priority
Authors: Jackson Roland
Published: February 2019

In 1856, an American woman, Eunice Foote, discovered the absorption of thermal radiation by carbon dioxide and water vapour. That was three years before John Tyndall, who is generally credited with this important discovery—a cornerstone of our current understanding of the greenhouse effect, climate change, weather and meteorology. Tyndall did not reference Foote's work. From a contemporary perspective, one might expect that Tyndall would have known of her findings. But it appears that he did not, raising deeper historical questions about the connections and relationships between American and European physicists in the mid nineteenth century. The discovery is seen as a significant moment in physics generally and in climate science in particular, and demands a proper analysis. This paper explores the argument about priority, and the issues that the episode highlights in terms of simultaneous discovery, the development of science in America, gender, amateur status, the reputation of American science in Europe and the networks and means of communication between researchers in America and Europe in the 1850s.
Morphogenesis and axis specification occur in parallel during optic cup and optic fissure formation, differentially modulated by BMP and Wnt
Authors: Eckert Priska , Knickmeyer Max D. , Schütz Lucas , Wittbrodt Joachim , Heermann Stephan
Published: February 2019

Optic cup morphogenesis is an intricate process. Especially, the formation of the optic fissure is not well understood. Persisting optic fissures, termed coloboma, are frequent causes for congenital blindness. Even though the defective fusion of the fissure margins is the most acknowledged reason for coloboma, highly variable morphologies of coloboma phenotypes argue for a diverse set of underlying pathomechanisms. Here, we investigate optic fissure morphogenesis in zebrafish to identify potential morphogenetic defects resulting in coloboma. We show that the formation of the optic fissure depends on tissue flow movements, integrated into the bilateral distal epithelial flow forming the optic cup. On the temporal side, the distal flow translates into a ventral perpendicular flow, shaping the temporal fissure margin. On the nasal side, however, the distal flow is complemented by tissue derived from the optic stalk, shaping the nasal fissure margin. Notably, a distinct population of TGFβ-signalling positive cells is translocated from the optic stalk into both fissure margins. Furthermore, we show that induced BMP signalling as well as Wnt-signalling inhibition result in morphogenetic defects of the optic fissure. Our data also indicate that morphogenesis is crucial for a proper positioning of pre-specified dorsal–ventral optic cup domains.
Violent video game engagement is not associated with adolescents' aggressive behaviour: evidence from a registered report
Authors: Przybylski Andrew K. , Weinstein Netta
Published: February 2019

In this study, we investigated the extent to which adolescents who spend time playing violent video games exhibit higher levels of aggressive behaviour when compared with those who do not. A large sample of British adolescent participants (
n
= 1004) aged 14 and 15 years and an equal number of their carers were interviewed. Young people provided reports of their recent gaming experiences. Further, the violent contents of these games were coded using official EU and US ratings, and carers provided evaluations of their adolescents' aggressive behaviours in the past month. Following a preregistered analysis plan, multiple regression analyses tested the hypothesis that recent violent game play is linearly and positively related to carer assessments of aggressive behaviour. Results did not support this prediction, nor did they support the idea that the relationship between these factors follows a nonlinear parabolic function. There was no evidence for a critical tipping point relating violent game engagement to aggressive behaviour. Sensitivity and exploratory analyses indicated these null effects extended across multiple operationalizations of violent game engagement and when the focus was on another behavioural outcome, namely, prosocial behaviour. The discussion presents an interpretation of this pattern of effects in terms of both the ongoing scientific and policy debates around violent video games, and emerging standards for robust evidence-based policy concerning young people's technology use.
Towards population genomics in non-model species with large genomes: a case study of the marine zooplanktonCalanus finmarchicus
Authors: Choquet Marvin , Smolina Irina , Dhanasiri Anusha K. S. , Blanco-Bercial Leocadio , Kopp Martina , Jueterbock Alexander , Sundaram Arvind Y. M. , Hoarau Galice
Published: February 2019

Advances in next-generation sequencing technologies and the development of genome-reduced representation protocols have opened the way to genome-wide population studies in non-model species. However, species with large genomes remain challenging, hampering the development of genomic resources for a number of taxa including marine arthropods. Here, we developed a genome-reduced representation method for the ecologically important marine copepodCalanus finmarchicus(haploid genome size of 6.34 Gbp). We optimized a capture enrichment-based protocol based on 2656 single-copy genes, yielding a total of 154 087 high-quality SNPs inC. finmarchicusincluding 62 372 in common among the three locations tested. The set of capture probes was also successfully applied to the congenericC. glacialis. Preliminary analyses of these markers revealed similar levels of genetic diversity between the twoCalanusspecies, while populations ofC. glacialisshowed stronger genetic structure compared toC. finmarchicus. Using this powerful set of markers, we did not detect any evidence of hybridization betweenC. finmarchicusandC. glacialis. Finally, we propose a shortened version of our protocol, offering a promising solution for population genomics studies in non-model species with large genomes.
Enhancement of the electrochemical properties of commercial coconut shell-based activated carbon by H
2
O dielectric barrier discharge plasma
Authors: Wang Xin , Zhou Xiaoyan , Chen Weimin , Chen Minzhi , Liu Chaozheng
Published: February 2019

Commercial coconut shell-based activated carbon (CSAC) has low specific capacitance and specific capacitance retention owing to its undeveloped pore structure and low proportion of heteroatoms. In this study, dielectric barrier discharge plasma was used to enhance the specific capacitance and rate capability of CSAC. H
2
O was used as an excited medium to introduce oxygen functional groups. The physico-chemical properties of CSAC and CSAC modified by H
2
O plasma (HCSAC) were revealed by automated surface area and pore size analysis, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and Raman spectroscopy. Electrochemical work was applied to investigate the electrochemical properties of CSAC and HCSAC. The results obtained showed that plasma modification improved the specific capacitance of CSAC by 64.8% (current density, 1 A g
−1
; electrolyte, 6 M KOH solution) within 100 s. This result is ascribed to the oxygen functional groups introduced to the surface of CSAC. It can also improve the hydrophilicity and wettability of the carbon surface leading to an increase from 76.7% to 84.6% in specific capacitance retention. Furthermore, H
2
O plasma modification can introduce oxygen functional groups without destroying the initial pore structures of CSAC. In summary, we provide a simple, fast, environment-friendly modification method to enhance the electrochemical properties of CSAC.
Eco-friendly synthesis of VO
2
with stripped pentavalent vanadium solution extracted from vanadium-bearing shale by hydrothermal process in high conversion rate
Authors: Kang Qian , Zhang Yimin , Bao Shenxu , Zhang Guobin
Published: February 2019

VO
2
(B) has shown excellent cathode performance in lithium batteries and become a hot research topic in recent years. A stripped vanadium solution extracted from vanadium-bearing shale containing a high concentration of vanadium and certain amounts of impurities was used as a vanadium source to synthesize VO
2
(B) by hydrothermal process. The VO
2
conversion rate can reach as high as 99.47% in a reaction time of 8 h, and this is the highest result reported. The crystalline structure and morphology of the synthesized products were characterized by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). Furthermore, the electrochemical properties of VO
2
(B) in lithium-ion batteries were investigated. The results indicated that the VO
2
(B) has the initial specific discharge capacity of 192.0 mAh g
−1
. Stripped vanadium solution is a raw material for producing V
2
O
5
and NH
4
VO
3
, which are indispensable vanadium sources in VO
2
synthesis. Therefore, synthesis of VO
2
via hydrothermal reduction by oxalic acid using stripped vanadium solution extracted from vanadium-bearing shale as a direct vanadium source is an eco-friendly, innovative and efficient method, and will have a great impact on VO
2
synthesis.
Phylogeny matters: revisiting ‘a comparison of bats and rodents as reservoirs of zoonotic viruses’
Authors: Guy Cylita , Thiagavel Jeneni , Mideo Nicole , Ratcliffe John M.
Published: February 2019

Diseases emerging from wildlife have been the source of many major human outbreaks. Predicting key sources of these outbreaks requires an understanding of the factors that explain pathogen diversity in reservoir species. Comparative methods are powerful tools for understanding variation in pathogen diversity and rely on correcting for phylogenetic relatedness among reservoir species. We reanalysed a previously published dataset, examining the relative effects of species' traits on patterns of viral diversity in bats and rodents. We expanded on prior work by using more highly resolved phylogenies for bats and rodents and incorporating a phylogenetically controlled principal components analysis. For rodents, sympatry and torpor use were important predictors of viral richness and, as previously reported, phylogeny had minimal impact in models. For bats, in contrast to prior work, we find that phylogeny does have an effect in models. Patterns of viral diversity in bats were related to geographical distribution (i.e. latitude and range size) and life history (i.e. lifespan, body size and birthing frequency). However, the effects of these predictors were marginal relative to citation count, emphasizing that the ability to accurately assess reservoir status largely depends on sampling effort and highlighting the need for additional data in future comparative studies.
Sulfur-free synthesis of size tunable rickardite (Cu

3−
x

Te
2
) spheroids and planar squares
Authors: Jia Guanwei , Wang Chengduo , Yang Peixu , Liu Jinhui , Zhang Weidong , Li Rongbin , Zhang Shaojun , Du Jiang
Published: February 2019

We report a novel synthesis of monodisperse samples of copper telluride with crystallinity and stoichiometry corresponding to forms of rickardite, Cu

3−
x

Te
2
(
x
< 1). This synthesis makes use of a ligand balanced reaction to allow control over shape and size by varying the relative and absolute concentration of oleylamine to stearic acid. The rickardite samples presented here display size dependent plasmon peaks in the near infrared and direct energy band gaps between 1.7 and 2.3 eV. As such they may find utility in photovoltaic, thermoelectric or as novel optical materials for study of surface plasmons.
A non-canonical arm of UPRER mediates longevity through ER remodeling and lipophagy
Authors: Daniele Joseph R. , Higuchi-Sanabria Ryo , Ramachandran Vidhya , Sanchez Melissa , Durieux Jenni , Tronnes Sarah U. , Paul Joseph W. , Esping Daniel J. , Monshietehadi Samira , Metcalf Melissa G. , Dillin Andrew
Published: February 2019

Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms implicated in regulating lifespan extension is the ability to induce protein chaperones to promote protein homeostasis. However, it is unclear whether protein chaperones exclusively regulate longevity. Previous work has shown that activating the unfolded protein response of the endoplasmic reticulum (UPRER) in neurons can signal peripheral tissues to promote chaperone expression, thus enhancing organismal stress resistance and extending lifespan. Here, we find that this activation not only promotes chaperones, but facilitates a dramatic restructuring of ER morphology in intestinal cells. This restructuring, which includes depletion of lipid droplets, ER expansion, and ER tubulation, depends of lipophagy. Surprisingly, we find that lipophagy is required for lifespan extension and is completely independent of chaperone function. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the canonical arm through protein chaperones, and a non-canonical mechanism through lipid depletion. In summary, our study identifies lipophagy as an integral component of UPRER-induced longevity.
Surpassing thermodynamic, kinetic, and stability barriers to isomerization catalysis for tagatose biosynthesis
Authors: Bober Josef R , Nair Nikhil
Published: February 2019

There are many enzymes that are relevant for making rare and valuable chemicals that while active, are severely limited by thermodynamic, kinetic, or stability issues (e.g. isomerases, lyases, transglycosidase etc.). In this work, we study an enzymatic reaction system −Lactobacillus sakeiL-arabinose isomerase (LsLAI) for D-galactose to D-tagatose isomerization – that is limited by all three reaction parameters. The enzyme has a low catalytic efficiency for non-natural substrate galactose, has low thermal stability at temperatures > 40 °C, and equilibrium conversion < 50%. After exploring several strategies to overcome these limitations, we finally show that encapsulating the enzyme in a gram-positive bacterium (Lactobacillus plantarum) that is chemically permeabilized can enable reactions at high rates, high conversion, and at high temperatures. The modified whole cell system stabilizes the enzyme, differentially partitions substrate and product across the membrane to shift the equilibrium toward product formation enables rapid transport of substrate and product for fast kinetics. In a batch process, this system enables approximately 50 % conversion in 4 h starting with 300 mM galactose (an average productivity of 37 mM/h), and 85 % conversion in 48 h, which are the highest reported for food-safe mesophilic tagatose synthesis. We suggest that such an approach may be invaluable for other enzymatic processes that are similarly kinetically-, thermodynamically-, and/or stability-limited.
Medusa: software to build and analyze ensembles of genome-scale metabolic network reconstructions
Authors: Medlock Gregory L. , Papin Jason A.
Published: February 2019

Uncertainty in the structure and parameters of networks is ubiquitous across computational biology. In constraint-based reconstruction and analysis of metabolic networks, this uncertainty is present both during the reconstruction of networks and in simulations performed with them. Here, we present Medusa, a Python package for the generation and analysis of ensembles of genome-scale metabolic network reconstructions. Medusa builds on the COBRApy package for constraint-based reconstruction and analysis by compressing a set of models into a compact ensemble object, providing functions for the generation of ensembles using experimental data, and extending constraint-based analyses to ensemble scale. We demonstrate how Medusa can be used to generate ensembles, perform ensemble simulations, and how machine learning can be used in conjunction with Medusa to guide the curation of genome-scale metabolic network reconstructions. Medusa is available under the permissive MIT license from the Python Packaging Index (https://pypi.org/) and from github (https://github.com/gregmedlock/Medusa/), and comprehensive documentation is available at https://medusa.readthedocs.io/en/latest/.
Glia-derived exosomal miR-274 targets Sprouty in trachea and synaptic boutons to modulate growth and responses to hypoxia
Authors: Tsai Yi-Wei , Sung Hsin-Ho , Li Jian-Chiuan , Yeh Chun-Yen , Chen Pei-Yi , Cheng Ying-Ju , Chen Chun-Hong , Tsai Yu-Chen , Chien Cheng-Ting
Published: February 2019

Secreted exosomal miRNAs mediate inter-organ/tissue communication by downregulating gene expression, thereby modulating developmental and physiological functions. However, the source, route, and function have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas precursor miR-274 was expressed in glia, mature miR-274 was secreted. miR-274 secretion to circulating hemolymph was detected in exosomes, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. miR-274 downregulated Sprouty to activate MAPK in synaptic boutons and tracheal branches, thereby promoting their growth. Expression of miR-274 solely in glia of amir-274null mutant reset normal levels of Sprouty and MAPK, and hemolymphatic exosomal miR-274.mir-274mutant larvae were hypersensitive to hypoxia, which was suppressed by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.
rhizoTrak: A flexible open source Fiji plugin for user-friendly manual annotation of time-series images from minirhizotrons
Authors: Möller Birgit , Chen Hongmei , Schmidt Tino , Zieschank Axel , Patzak Roman , Türke Manfred , Weigelt Alexandra , Posch Stefan
Published: February 2019

Background and aims

Minirhizotrons are commonly used to study root turnover which is essential for understanding ecosystem carbon and nutrient cycling. Yet, extracting data from minirhizotron images requires intensive annotation effort. Existing annotation tools often lack flexibility and provide only a subset of the required functionality. To facilitate efficient root annotation in minirhizotrons, we present the user-friendly open source tool rhizoTrak.

Methods and results

rhizoTrak builds on TrakEM2 and is publically available as Fiji plugin. It uses treelines to represent branching structures in roots and assigns customizable status labels per root segment. rhizoTrak offers configuration options for visualization and various functions for root annotation mostly accessible via keyboard shortcuts. rhizoTrak allows time-series data import and particularly supports easy handling and annotation of time series images. This is facilitated via explicit temporal links (connectors) between roots which are automatically generated when copying annotations from one image to the next. rhizoTrak includes automatic consistency checks and guided procedures for resolving conflicts. It facilitates easy data exchange with other software by supporting open data formats.

Conclusions

rhizoTrak covers the full range of functions required for user-friendly and efficient annotation of time-series images. Its flexibility and open source nature will foster efficient data acquisition procedures in root studies using minirhizotrons.
Genuine cross-frequency coupling networks in human resting-state electrophysiological recordings
Authors: Siebenhühner Felix , Wang Sheng H , Arnulfo Gabriele , Lampinen Anna , Nobili Lino , Palva J. Matias , Palva Satu
Published: February 2019

Phase synchronization of neuronal oscillations in specific frequency bands coordinates anatomically distributed neuronal processing and communication. Typically, oscillations and synchronization take place concurrently in many distinct frequencies, which serve separate computational roles in cognitive functions. While within-frequency phase synchronization has been studied extensively, less is known about the mechanisms that govern neuronal processing distributed across frequencies and brain regions. Such integration of processing between frequencies could be achieved via cross-frequency coupling (CFC), either by phase-amplitude coupling (PAC) or byn:m-cross-frequency phase synchrony (CFS). So far, studies have mostly focused on local CFC in individual brain regions, whereas the presence and functional organization of CFC between brain areas have remained largely unknown. We posit that inter-areal CFC may be essential for large-scale coordination of neuronal activity and investigate here whether genuine CFC networks are present in human resting-state brain activity.

To assess the functional organization of CFC networks, we identified brain-wide CFC networks at meso-scale resolution from stereo-electroencephalography (SEEG) and at macro-scale resolution from source-reconstructed magnetoencephalography (MEG) data. We developed a novel graph-theoretical method to distinguish genuine CFC from spurious CFC that may arise from non-sinusoidal signals ubiquitous in neuronal activity. We show that genuine inter-areal CFC is present in human resting-state activity in both MEG and SEEG data. Both CFS and PAC networks coupled theta and alpha oscillations with higher frequencies in large-scale networks connecting anterior and posterior brain regions. CFS and PAC networks had distinct spectral patterns and opposing distribution of low- and high frequency network hubs, implying that they constitute distinct CFC mechanisms. The strength of CFS networks was also predictive of cognitive performance in a separate neuropsychological assessment. In conclusion, these results provide evidence for inter-areal CFS and PAC being two distinct mechanisms for coupling oscillations across frequencies in large-scale brain networks.
Generating High Density, Low Cost Genotype Data in Soybean [Glycine max (L.) Merr.]
Authors: Happ Mary M. , Wang Haichuan , Graef George L. , Hyten David L.
Published: February 2019

Obtaining genome-wide genotype information for millions of SNPs in soybean [Glycine max (L.) Merr.] often involves completely resequencing a line at 5X or greater coverage. Currently, hundreds of soybean lines have been resequenced at high depth levels with their data deposited in the NCBI short read achieve. This publicly available dataset may be leveraged as an imputation reference panel in combination with skim (low coverage) sequencing of new soybean genotypes to economically obtain high-density SNP information. Ninety-nine soybean lines resequenced at an average of 17.1X were used to generate a reference panel, with over 10 million SNPs called using GATK’s Haplotype Caller tool. Whole genome resequencing at approximately 1X depth was performed on 114 previously ungenotyped experimental soybean lines. Coverages down to 0.1X were analyzed by randomly subsetting raw reads from the original 1X sequence data. SNPs discovered in the reference panel were genotyped in the experimental lines after aligning to the soybean reference genome, and missing markers imputed using Beagle 4.1. Sequencing depth of the experimental lines could be reduced to 0.3X while still retaining an accuracy of 97.8%. Accuracy was inversely related to minor allele frequency, and highly correlated with marker linkage disequilibrium. The high accuracy of skim sequencing combined with imputation provides a low cost method for obtaining dense genotypic information that can be used for various genomics applications in soybean.
EPI distortion correction for simultaneous human brain stimulation and imaging at 3T
Authors: Oh Hyuntaek , Kim Jung Hwan , Yau Jeffrey M.
Published: February 2019

Transcranial magnetic stimulation (TMS) can be paired with functional magnetic resonance imaging (fMRI) in simultaneous TMS-fMRI experiments. These multimodal experiments enable causal probing of network architecture in the human brain which can complement alternative network mapping approaches. Critically, merely introducing the TMS coil into the scanner environment can sometimes produce substantial magnetic field inhomogeneities and spatial distortions which limit the utility of simultaneous TMS-fMRI. We assessed the efficacy of point spread function corrected echo planar imaging (PSF-EPI) in correcting for the field inhomogeneities associated with a TMS coil at 3T. In phantom and brain scans, we quantitatively compared the coil-induced distortion artifacts measured in PSF-EPI scans to artifacts measured in conventional echo-planar imaging (EPI) and a simultaneous multi-slice sequence (SMS)-EPI. While we observed substantial coil-related artifacts in the data produced by the conventional EPI and SMS sequences, PSF-EPI produced data that had significantly greater signal-to-noise and less distortions. In phantom scans with the PSF-EPI sequence, we also characterized the temporal profile of dynamic artifacts associated with TMS delivery and found that image quality remained high as long as the TMS pulse preceded the RF excitation pulses by at least 50ms. Lastly, we validated the PSF-EPI sequence in human brain scans involving TMS and motor behavior as well as resting state fMRI scans. Our collective results demonstrate the superiority of PSF-EPI over conventional EPI and SMS sequences for simultaneous TMS-fMRI when coil-related artifacts are a concern. The ability to collect high quality resting state fMRI data in the same session as the simultaneous TMS-fMRI experiment offers a unique opportunity to interrogate network architecture in the human brain.
Tracking the emergence of location-based spatial representations in human scene-selective cortex
Authors: Berens Sam C. , Joensen Bárður H , Horner Aidan J.
Published: February 2019

Scene-selective regions of the human brain form allocentric representations of locations in our environment. These representations are independent of heading direction and allow us to know where we are regardless of our direction of travel. However, we know little about how these location-based representations are formed. Using fMRI representational similarity analysis and linear mixed-models, we tracked the emergence of location-based representations in scene-selective brain regions. We estimated patterns of activity for two distinct scenes, taken before and after participants learnt they were from the same location. During a learning phase, we presented participants with two types of panoramic videos: (1) an overlap video condition displaying two distinct scenes (0° and 180°) from the same location, and (2) a no-overlap video displaying two distinct scenes from different locations (that served as a control condition). In the parahippocampal cortex (PHC) and retrosplenial cortex (RSC), representations of scenes from the same location became more similar to each other only after they had been shown in the overlap condition, suggesting the emergence of viewpoint-independent location-based representations. Whereas these representations emerged in the PHC regardless of task performance, RSC representations only emerged for locations where participants could behaviourally identify the two scenes as belonging to the same location. The results suggest that we can track the emergence of location-based representations in the PHC and RSC in a single fMRI experiment. Further, they support computational models that propose the RSC plays a key role in transforming viewpoint-independent representations into behaviourally-relevant representations of specific viewpoints.
A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion
Authors: Zambuto Samantha G. , Clancy Kathryn B.H. , Harley Brendan A.C.
Published: February 2019

As the lining of the uterus and site of blastocyst implantation, the endometrium is a dynamic tissue that undergoes rapid cycles of growth, breakdown, and remodeling each menstrual cycle. Significant vascular remodeling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodeling enhance blood flow to the embryo ahead of placentation. Insight into endometrial vascular remodeling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective for this study was to develop a tissue engineering platform to investigate processes of endometrial angiogenesis and trophoblast invasion in a 3D environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue. Further, the hydrogel supports the formation of stable endometrial endothelial cell networks and attachment of a stratified endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment, and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.
Repressive gene regulation synchronizes development with cellular metabolism
Authors: Cassidy Justin J. , Bernasek Sebastian , Bakker Rachael , Giri Ritika , Peláez Nicolás , Eder Bryan , Bobrowska Anna , Bagheri Neda , Amaral Luis A. Nunes , Carthew Richard W.
Published: February 2019

Metabolic conditions affect the developmental tempo of most animal species. Consequently, developmental gene regulatory networks (GRNs) must faithfully adjust their dynamics to a variable time scale. We find evidence that layered weak repression of genes provides the necessary coupling between GRN output and cellular metabolism. Using a mathematical model that replicates such a scenario, we find that lowering metabolism corrects developmental errors that otherwise occur when different layers of repression are lost. Through mutant analysis, we show that gene expression dynamics are unaffected by loss of repressors, but only when cellular metabolism is reduced. We further show that when metabolism is lowered, formation of a variety of sensory organs inDrosophilais normal despite loss of individual repressors of transcription, mRNA stability, and protein stability. We demonstrate the universality of this phenomenon by experimentally eliminating the entire microRNA family of repressors, and find that all microRNAs are rendered unnecessary when metabolism is reduced. Thus, layered weak repression provides robustness through error frequency suppression, and may provide an evolutionary route to a shorter reproductive cycle.
Single-cell RNA sequencing of a European and an African lymphoblastoid cell line
Authors: Osorio Daniel , Yu Xue , Yu Peng , Serpedin Erchin , Cai James J.
Published: February 2019

In biomedical research, lymphoblastoid cell lines (LCLs), often established byin vitroinfection of resting B cells with Epstein Barr Virus, are commonly used as surrogates for peripheral blood lymphocytes. Genomic and transcriptomic information on LCLs has been used to study the impact of genetic variation on gene expression in humans. Here we present single-cell RNA sequencing (scRNA-seq) data on GM12878 and GM18502—two LCLs derived from the blood of female donors of European and African ancestry, respectively. Cells from three samples (the two LCLs and a 1:1 mixture of the two) were prepared separately using a 10X Genomics Chromium Controller and deeply sequenced. The final dataset contained 7,045 cells from GM12878, 5,189 from GM18502, and 5,820 from the mixture, offering valuable information on single-cell gene expression in highly homogenous cell populations. This dataset is a suitable reference of population differentiation in gene expression at the single-cell level. Data from the mixture provides additional valuable information facilitating the development of statistical methods for data normalization and batch effect correction.
MicroRNA-143 plays a protective role in ischemia-induced retinal neovascularization
Authors: Wang Jiang-Hui , Chen Jinying , Ling Damien , Tu Leilei , Singh Vikrant , Riaz Moeen , Li Fan , Prea Selwyn M. , He Zheng , Bui Bang V. , Hewitt Alex W. , van Wijngaarden Peter , Dusting Gregory J. , Liu Guei-Sheung
Published: February 2019

Retinal neovascularization is a severe complication of proliferative diabetic retinopathy. MicroRNAs (miRNAs) are master regulators of gene expression that play important roles in retinal neovascularization. Here, we investigated the retinal miRNA expression profile in a rat model of oxygen-induced retinopathy (OIR) through miRNA-Seq. We found that miR-143-3p, miR-126-3p, miR-150-5p and miR-145-5p were significantly down-regulated in the retina of OIR rats, and directly involved in the development of retinal neovascularization. Of these identified miRNAs, miR-143 is enriched in retina and was first reported being associated with pathological retinal angiogenesis. Our RNA-Seq data further suggested that miR-143 alleviates retinal neovascularization by mediating the inflammation/stress pathways via Fos. Moreover, the computational analysis indicated that Transforming Growth Factor-beta Activated Kinase 1 (TAK1) is involved in several key pathways associated with the dysregulated miRNAs. The pharmacological inhibition of TAK1 suppressed angiogenesis in vitro and retinal neovascularization in vivo. Our data highlight the utility of next-generation sequencing in the development of therapeutics for ocular neovascularization and further suggest that therapeutic targeting the dysregulated miRNAs or TAK1 may be a feasible adjunct therapeutic approach in patients with retinal neovascularization.
Structure of the Ebola virus nucleoprotein – RNA complex
Authors: Kirchdoerfer Robert N. , Saphire Erica Ollmann , Ward Andrew B.
Published: February 2019

Ebola virus is an emerging virus capable of causing a deadly disease in humans. Replication, transcription and packaging of the viral genome is carried out by the viral nucleocapsid. The nucleocapsid is a complex of the viral nucleoprotein, RNA and several other viral proteins. The nucleoprotein NP forms large, RNA-bound, helical filaments and acts as a scaffold for additional viral proteins. The 3.1 Å single-particle cryo-electron microscopy structure of the nucleoprotein-RNA helical filament presented here resembles previous structures determined at lower resolution while providing improved molecular details of protein-protein and protein-RNA interactions. The higher resolution of the structure presented here will facilitate the design and characterization of novel and specific Ebola virus therapeutics targeting the nucleocapsid.

Synopsis

The 3.1 Å single-particle cryo-electron microscopy structure of the RNA-bound, Ebola virus nucleoprotein helical filament provides molecular details of protein-protein and protein-RNA interactions.
Repeated treatment with cocaine or methamphetamine increases CRF2 and decreases astrocytic markers in the ventral tegmental area and substantia nigra
Authors: Sharpe Amanda L. , Trzeciak Marta , Douglas Phillip , Beckstead Michael J.
Published: February 2019

Dopamine neurons in the substantia nigra (SN) and ventral tegmental area (VTA) play a crucial role in the reinforcing properties of abused drugs including methamphetamine and cocaine. Evidence also suggests the involvement of non-dopaminergic transmitters, including glutamate and the stress-related peptide corticotropin-releasing factor (CRF), on the chronic effects of psychostimulants in the SN/VTA. Astrocytes express a variety of membrane-bound neurotransmitter receptors and transporters which influence neurotransmission in the SN/VTA. CRF2 activity in the VTA is important for stress-induced relapse and drug-seeking behavior, but the localization of its effects are not completely understood. Here we used immunofluorescence to identify the effect of methamphetamine and cocaine administration on astrocytes, the glial glutamate transporter GLAST, and CRF2 in the SN/VTA. We treated adult male mice with i.p. injections of methamphetamine (3 mg/kg), cocaine (10 mg/kg), or saline for 12 days. Coronal brain sections were processed for immunofluorescence using S100β (marker for astrocytes), glial-specific glutamate/aspartate transporters (GLAST), and CRF2. The results showed a significant decrease in GLAST immunofluorescence in brains of mice treated with cocaine or methamphetamine compared to saline. In addition, we observed increased labelling of CRF2 in drug treated groups, a decrease in the number of S100β positive cells, and an increase in co-staining of these two markers. Our results suggest that administration of either methamphetamine or cocaine decreases astrocytic markers and increases immunoreactivity for CRF2 in the VTA, an effect that is most pronounced in S100β positive cells.
A null model of the mouse whole-neocortex micro-connectome
Authors: Reimann Michael W , Gevaert Michael , Shi Ying , Lu Huanxiang , Markram Henry , Muller Eilif
Published: February 2019

1

Connectomics, the study of the structure of networks of synaptically connected neurons, is one of the most important frontiers of neuroscience. Great advances are being made on the level of macro- and meso-scale connectomics, that is the study of how and which populations of neurons are wired together by tracing axons of anatomically and genetically defined neurons throughout the brain. Similarly, the use of electron-microscopy and statistical connectome models has improved our understanding of micro-connectomics, that is the study of connectivity patterns between individual neurons. We have combined these two complementary views of connectomics to build a first draft statistical model of the neuron-to-neuron micro-connectome of a whole mouse neocortex. We combined available data on region-to-region connectivity and individual whole-brain axon reconstructions to model in addition to the meso-scale trends also the innervation of individual neurons by individual axons, within and across regions. This process revealed a novel targeting principle that allowed us to predict the innervation logic of individual axons from meso-scale data. The resulting micro-connectome of 10 million neurons and 88 billion synapses recreates biological trends of targeting on the macro-meso- and micro-scale, i.e. targeting of brain regions, domains and layers within a brain region down to individual neurons. This openly accessible connectome can serve as a powerful null model to compare experimental findings to and as a substrate for whole-brain simulations of detailed neural networks.
Thermodynamic Measures of Human Brain Development from Fetal Stage to Adulthood
Authors: Rietman Edward A. , Taylor Sophie , Siegelmann Hava T. , Cavaglia Marco , Tuszynski Jack A.
Published: February 2019

This paper analyzes the data obtained from tissue samples of the human brains containing protein expression values. The data have been processed for their thermodynamic measure in terms of the Gibbs free energy of the corresponding protein-protein interaction networks. We have investigated the functional dependence of the Gibbs free energies on age and found consistent trends for most of the 16 main brain areas. The peak of the Gibbs energy values is found at birth with a trend toward plateauing at the age of maturity. We have also compared the data for males and females and uncovered functional differences for some of the brain regions.

Author Summary

In this paper we briefly outline the theoretical basis for a novel analysis of brain development in terms of a thermodynamic measure (Gibbs free energy) for the corresponding protein-protein interaction networks. We analyzed the overall developmental patterns for Gibbs free energy as a function of age across all brain regions. Of particular note was the significant upward trend in the fetal stages, which is generally followed by a sharp dip at birth and a plateau at maturity. We then compared the trends for female and male samples. A crossover pattern was observed for most of the brain regions, where the Gibbs free energy of the male samples were lower than the female samples at prenatal and neonatal ages, but higher at ages 8-40 finally converging at late adulthood.
Detection of classic and cryptic Strongyloides genotypes by deep amplicon sequencing: A preliminary survey of dog and human specimens collected from remote Australian communities
Authors: Beknazarova Meruyert , Barratt Joel L. N. , Bradbury Richard S. , Lane Meredith , Whiley Harriet , Ross Kirstin
Published: February 2019

Strongyloidiasis is caused by the human infective nematodes Strongyloides stercoralis, Strongyloides fuelleborni subsp. fuelleborni and Strongyloides fuelleborni subsp. kellyi. The zoonotic potential of S. stercoralis and the potential role of dogs in the maintenance of strongyloidiasis transmission has been a topic of interest and discussion for many years. In Australia, strongyloidiasis is prevalent in remote socioeconomically disadvantaged communities in the north of the continent. Being an isolated continent that has been separated from other regions for a long geological period, description of the diversity of Australian Strongyloides genotypes adds to our understanding of the genetic diversity within the genus. Using PCR enrichment combined with Illumina sequencing technology, we sequenced the Strongyloides SSU 18S rDNA hyper-variable I and hyper-variable IV regions using Strongyloides-specific primers, and a fragment of the mtDNA cox1 gene using primers that are broadly specific for Strongyloides sp. and hookworms. These loci were amplified from DNA extracted from Australian human and dog faeces, and one human sputum sample. Using this approach, we confirm for the first time that potentially zoonotic S. stercoralis genotypes are present in Australia, suggesting that dogs represent a potential reservoir of human strongyloidiasis in remote Australian communities.

Author summary

Strongyloides stercoralis is a soil-transmitted nematode that causes the disease strongyloidiasis. Due to the autoinfective nature of this parasite, it can re-infect a host causing chronic infection. If not diagnosed and treated it can be highly detrimental to human health and has a high mortality rate. Strongyloidiasis is common in remote communities in the north of Australia and has been an issue for decades. Despite various successful intervention programs to treat human strongyloidiasis, the disease remains endemic in those communities. Here for the first time we looked at the Australian dogs’ potential to infect humans and found that they carry two genetically distinct strains of Strongyloides spp., one of which also infects humans. This supports the hypothesis that dogs are a potential source for human strongyloidiasis. We also found that dogs in Australia might be carrying unique haplotypes. Whether these new haplotypes are also human infective is to be confirmed by further research.
Concomitant cocrystal and salt: no interconversion in the solid state
Authors: Losev Evgeniy A. , Boldyreva Elena
Published: February 2019

A cocrystal and a molecular salt of β-alanine and DL-tartaric acid, C3H8NO2
+·C4H4O6
−, of the same chemical composition, were studied over a wide temperature range by single-crystal and powder X-ray diffraction. Neither the interconversion between the two phases nor any polymorphic transitions were observed in the temperature range from 100 K to the melting points. This contrasts with the solvent-mediated phase transition from the salt to the cocrystal in a slurry that has been documented earlier.