bluuebunny/crossref_metadata_2025 huggingface dataset:
Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye: Implication to Glaucoma Surgery Site Selection
Authors: Wu Yifan , Seong Young Jin , Li Kin , Choi Dongwon , Park Eunkyung , Daghlian George H. , Jung Eunson , Bui Khoa , Zhao Luping , Madhavan Shrimika , Daghlian Saren , Daghlian Patill , Chin Desmond , Cho Il-Taeg , Wong Alex K. , Heur J. Martin , Zhang-Nunes Sandy , Tan James C. , Ema Masatsugu , Huang Alex S. , Hong Young-Kwon
Published: December 2019

Glaucoma surgeries, such as trabeculectomy, are performed to lower the intraocular pressure to reduce the risk of vision loss. The surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. However, the current knowledge of these ocular surface lymphatics remains limited. Here, we characterized the biology and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed by a primary lymphatic vessel that grows out from the nasal-side medial canthus region at the time of birth. This primary lymphatic vessel immediately branches out and invades the limbus and conjunctiva, and then simultaneously encircles the cornea in a bidirectional manner. As a result, the distribution of the ocular lymphatic is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic spouts are mainly produced from the nasal-side limbal lymphatics, posing the nasal side of the eye more responsive to fluid drainage and inflammatory stimuli. Consistently, when a fluorescent tracer was injected, fluid clearance was much more efficient in the nasal side than the temporal side of the eyes. In comparison, blood vessels are evenly distributed on the front surface of the eyes. We found that these distinct vascular distribution patterns were also conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a surgical site for glaucoma surgeries to improve the fluid drainage.
Schistocephalusparasite infection alters sticklebacks’ movement ability and thereby shapes social interactions
Authors: Jolles Jolle W. , Mazué Geoffrey P. F. , Davidson Jacob , Behrmann-Godel Jasminca , Couzin Iain D.
Published: December 2019

Parasitism is ubiquitous in the animal kingdom. Although many fundamental aspects of host-parasite relationships have been unravelled, few studies have systematically investigated how parasites affect organismal movement. Here we combine behavioural experiments ofSchistocephalus solidusinfected sticklebacks with individual-based simulations to understand how parasitism affects individual movement ability and how this in turn influences social interaction patterns. Detailed movement tracking revealed that infected fish swam slower, accelerated slower, turned more slowly, and tended to be more predictable in their movements than did non-infected fish. Importantly, the strength of these effects increased with increasing parasite load (% of body weight), with the behaviour of more heavily infected fish being more impaired. When grouped, pairs of infected fish moved more slowly, were less cohesive, less aligned, and less coordinated than healthy pairs. Mixed pairs exhibited intermediate behaviours and were primarily led by the non-infected fish. These social patterns emerged naturally in model simulations of self-organised groups composed of individuals with different speeds and turning tendency, consistent with changes in mobility and manoeuvrability due to infection. Together, our results demonstrate how infection with a complex life cycle parasite affects the movement ability of individuals and how this in turn shapes social interactions, providing important mechanistic insights into the effects of parasites on host movement dynamics.
Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan
Authors: Sakaue Saori , Kanai Masahiro , Karjalainen Juha , Akiyama Masato , Kurki Mitja , Matoba Nana , Takahashi Atsushi , Hirata Makoto , Kubo Michiaki , Matsuda Koichi , Murakami Yoshinori ,   FinnGen, Daly Mark J. , Kamatani Yoichiro , Okada Yukinori
Published: December 2019

Human genetics seeks a way to improve human health on a global scale. Expectations are running high for polygenic risk scores (PRSs) to be translated into clinical practice to predict an inborn susceptibility to health risks. While risk stratification based on PRS is one way to promote population health, a strategy to utilize genetics to prioritize modifiable risk factors and biomarkers driving heath outcome is also warranted. To this end, here we utilized PRSs to comprehensively investigate the association of the genetic susceptibility to complex traits with human lifespan in collaboration with three worldwide biobanks (ntotal = 675,898). First, we conducted genome-wide association studies for 45 quantitative clinical phenotypes, constructed the individual PRSs, and associated them with the age at death of 179,066 participants in BioBank Japan. The PRSs revealed that the genetic susceptibility of high systolic blood pressure (sBP) was strongly associated with a shorter lifespan (hazard ratio [HR] = 1.03, P = 1.4×10-7). Next, we sought to replicate these associations in individuals of European ancestry in UK Biobank (n = 361,194) and FinnGen (n = 135,638). Among the investigated traits, the individuals with higher blood pressure-related PRSs were trans-ethnically associated with a shorter lifespan (HR = 1.03, Pmeta = 3.9×10-13 for sBP) and parental lifespan (HR = 1.06, PUKBB = 2.0×10-86 for sBP). Further, our trans-biobank study identified additional complex traits associated with lifespan (e.g., obesity, height, serum lipids, and platelet counts). Of them, obesity-related traits showed strikingly heterogeneous effects on lifespan between Japanese and European populations (Pheterogeneity = 9.5×10-8 for body mass index). Through trans-ethnic biobank collaboration, we elucidated the novel value of the PRS study in genetics-driven prioritization of risk factors and biomarkers which can be medically intervened to improve population health.
Statistically-estimated tree biomass, stem density, and basal area for the upper Midwestern United States at the time of Euro-American settlement
Authors: Paciorek Christopher J. , Cogbill Charles V. , Peters Jody A. , Goring Simon J. , Williams John W. , Mladenoff David J. , Dawson Andria , McLachlan Jason S.
Published: December 2019

We present gridded 8 km-resolution data products of the estimated biomass, basal area, and stem density of tree taxa at the time of Euro-American settlement of the midwestern United States for the states of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The data come from settlement-era Public Land Survey (PLS) data (ca. 0.8-km resolution) of trees recorded by land surveyors. The surveyor notes have been transcribed, cleaned, and processed to estimate biomass, basal area, and stem density at individual points on the landscape. The point-level data are then aggregated within grid cells and statistically smoothed using a statistical model that accounts for zero-inflated continuous data with smoothing based on generalized additive modeling techniques and approximate Bayesian uncertainty estimates. We expect this data product to be useful for understanding the state of vegetation in the midwestern United States prior to large-scale Euro-American settlement. In addition to specific regional questions, the data product can serve as a baseline against which to investigate how forests and ecosystems change after intensive settlement. The data products (including both raw and statistically smoothed estimates at the 8-km scale) are being made available at the LTER network data portal as version 1.0.
Studying RNA–DNA interactome by Red-C identifies noncoding RNAs associated with repressed chromatin compartment and reveals transcription dynamics
Authors: Gavrilov Alexey A. , Zharikova Anastasiya A. , Galitsyna Aleksandra A. , Luzhin Artem V. , Rubanova Natalia M. , Golov Arkadiy K. , Petrova Nadezhda V. , Logacheva Maria D. , Kantidze Omar L. , Ulianov Sergey V. , Magnitov Mikhail D. , Mironov Andrey A. , Razin Sergey V.
Published: December 2019

Non-coding RNAs (ncRNAs) participate in various biological processes, including regulating transcription and sustaining genome 3D organization. Here, we present a method termed Red-C that exploits proximity ligation to identify contacts with the genome for all RNA molecules present in the nucleus. Using Red-C, we uncovered the RNA–DNA interactome of human K562 cells and identified hundreds of ncRNAs enriched in active or repressed chromatin, including previously undescribed RNAs. We found two microRNAs—MIR3648 and MIR3687 transcribed from the rRNA locus—that are associated with inactive chromatin genome wide. These miRNAs favor bulk heterochromatin over Polycomb-repressed chromatin and interact preferentially with late-replicating genomic regions. Analysis of the RNA–DNA interactome also allowed us to trace the kinetics of messenger RNA production. Our data support the model of co-transcriptional intron splicing, but not the hypothesis of the circularization of actively transcribed genes.
Do deep neural networks see the way we do?
Authors: Jacob Georgin , Pramod R. T. , Katti Harish , Arun S. P.
Published: December 2019

Deep neural networks have revolutionized computer vision, and their object representations match coarsely with the brain. As a result, it is widely believed that any fine scale differences between deep networks and brains can be fixed with increased training data or minor changes in architecture. But what if there are qualitative differences between brains and deep networks? Do deep networks even see the way we do? To answer this question, we chose a deep neural network optimized for object recognition and asked whether it exhibits well-known perceptual and neural phenomena despite not being explicitly trained to do so. To our surprise, many phenomena were present in the network, including the Thatcher effect, mirror confusion, Weber’s law, relative size, multiple object normalization and sparse coding along multiple dimensions. However, some perceptual phenomena were notably absent, including processing of 3D shape, patterns on surfaces, occlusion, natural parts and a global advantage. Our results elucidate the computational challenges of vision by showing that learning to recognize objects suffices to produce some perceptual phenomena but not others and reveal the perceptual properties that could be incorporated into deep networks to improve their performance.
Auditory enhancement of illusory contour perception
Authors: Tivadar Ruxandra I. , Gaglianese Anna , Murray Micah M.
Published: December 2019

Illusory contours (ICs) are borders that are perceived in the absence of contrast gradients. Until recently, IC processes were considered exclusively visual in nature and presumed to be unaffected by information from other senses. Electrophysiological data in humans indicates that sounds can enhance IC processes. Despite cross-modal enhancement being observed at the neurophysiological level, to date there is no evidence of direct amplification of behavioural performance in IC processing by sounds. We addressed this knowledge gap. Healthy adults (N=15) discriminated instances when inducers were arranged to form an IC from instances when no IC was formed (NC). Inducers were low-constrast and masked, and there was continuous background acoustic noise throughout a block of trials. On half of the trials, i.e. independently of IC vs. NC, a 1000Hz tone was presented synchronously with the inducer stimuli. Sound presence improved the accuracy of indicating when an IC was presented, but had no impact on performance with NC stimuli (significant IC presence/absence × Sound presence/absence interaction). There was no evidence that this was due to general alerting or to a speed-accuracy trade-off (no main effect of sound presence on accuracy rates and no comparable significant interaction on reaction times). Moreover, sound presence increased sensitivity and reduced bias on the IC vs. NC discrimination task. These results demonstrate that multisensory processes augment mid-level visual functions, exemplified by IC processes. Aside from the impact on neurobiological and computational models of vision our findings may prove clinically beneficial for low-vision or sight-restored patients.
A minimal CRISPR-Cas3 system for genome engineering
Authors: Csörgő Bálint , León Lina M. , Chau-Ly Ilea J. , Vasquez-Rifo Alejandro , Berry Joel D. , Mahendra Caroline , Crawford Emily D. , Lewis Jennifer D. , Bondy-Denomy Joseph
Published: December 2019

CRISPR-Cas technologies have provided programmable gene editing tools that have revolutionized research. The leading CRISPR-Cas9 and Cas12a enzymes are ideal for programmed genetic manipulation, however, they are limited for genome-scale interventions. Here, we utilized a Cas3-based system featuring a processive nuclease, expressed endogenously or heterologously, for genome engineering purposes. Using an optimized and minimal CRISPR-Cas3 system (Type I-C) programmed with a single crRNA, large deletions ranging from 7 - 424 kb were generated in Pseudomonas aeruginosa with high efficiency and speed. By comparison, Cas9 yielded small deletions and point mutations. Cas3-generated deletion boundaries were variable in the absence of a homology-directed repair (HDR) template, and successfully and efficiently specified when present. The minimal Cas3 system is also portable; large deletions were induced with high efficiency in Pseudomonas syringae and Escherichia coli using an “all-in-one” vector. Notably, Cas3 generated bi-directional deletions originating from the programmed cut site, which was exploited to iteratively reduce a P. aeruginosa genome by 837 kb (13.5%) using 10 distinct crRNAs. We also demonstrate the utility of endogenous Cas3 systems (Type I-C and I-F) and develop an “anti-anti-CRISPR” strategy to circumvent endogenous CRISPR-Cas inhibitor proteins. CRISPR-Cas3 could facilitate rapid strain manipulation for synthetic biological and metabolic engineering purposes, genome minimization, and the analysis of large regions of unknown function.
Differences in berry primary and secondary metabolisms identified by transcriptomic and metabolic profiling of two table grape color somatic variants
Authors: Santibáñez Claudia , Meyer Carlos , Martínez Litsy , Moyano Tomás , Lunn John , Feil Regina , Dai Zhanwu , Carrasco David , Arroyo-García Rosa , Hilbert Ghislaine , Renaud Christel , Delrot Serge , Manke-Nachtigall Fabiane , Gutiérrez Rodrigo , Matus José Tomás , Gomès Eric , Arce-Johnson Patricio
Published: December 2019

Anthocyanins are flavonoids responsible for the color of berries in skin-pigmented grapevine (Vitis vinifera L.). Due to the widely adopted vegetative propagation of this species, somatic mutations occurring in meristematic cell layers can be fixed and passed into the rest of the plant when cloned. In this study we focused on the transcriptomic and metabolic differences between two color somatic variants. Using microscopic, metabolic and mRNA profiling analyses we compared the table grape cultivar (cv.) ‘Red Globe’ (RG, with purplish berry skin) and cv. ‘Chimenti Globe’ (CG, with a contrasting reddish berry skin color). As expected, significant differences were found in the composition of flavonoids and other phenylpropanoids, but also in their upstream precursors’ shikimate and phenylalanine. Among primary metabolites, sugar phosphates related with sucrose biosynthesis were less accumulated in cv. ‘CG’. The red-skinned cv. ‘CG’ only contained di-hydroxylated anthocyanins (i.e. peonidin and cyanidin) while the tri-hydroxylated derivatives malvidin, delphinidin and petunidin were absent, in correlation to the reddish cv. ‘CG’ skin coloration. Transcriptomic analysis showed alteration in flavonoid metabolism and terpenoid pathways and in primary metabolism such as sugar content. Eleven flavonoid 3’5’-hydroxylase gene copies were down-regulated in cv. ‘CG’. This family of cytochrome P450 oxidoreductases are key in the biosynthesis of tri-hydroxylated anthocyanins. Many transcription factors appeared down-regulated in cv. ‘CG’ in correlation to the metabolic and transcriptomic changes observed. The use of molecular markers and its confirmation with our RNA-seq data showed the exclusive presence of the null MYBA2 white allele (i.e. homozygous in both L1 and L2 layers) in the two somatic variants. Therefore, the differences in MYBA1 expression seem sufficient for the skin pigmentation differences and the changes in MYBA target gene expression in cv. ‘Chimenti Globe’.
Sex enhances survival inParamecium
Authors: Thind Amarinder Singh , Vitali Valerio , Guarracino Mario R. , Catania Francesco
Published: December 2019

The pervasiveness of sex despite its well-known costs is a long-standing puzzle in evolutionary biology. Current explanations for the success of sex in nature largely rely on the adaptive significance of the new or rare genotypes that sex may generate. Less explored is the possibility that sex-underlying molecular mechanisms can enhance fitness and convey benefits to the individuals that bear the immediate costs of sex. Here we show that self-fertilization can increase stress resistance in the ciliateParamecium tetraurelia. This advantage is independent of new genetic variation, coupled with a reduced nutritional input, and offers fresh insights into the mechanistic origin of sex. In addition to providing evidence that the molecular underpinnings of sexual reproduction and the stress response are linked inP. tetraurelia, these findings supply an explanation for the persistence of self-fertilization in this ciliate.
Conserved and specific genomic features of endogenous polydnaviruses revealed by whole genome sequencing of two ichneumonid wasps
Authors: Legeai Fabrice , Santos Bernardo F. , Robin Stéphanie , Bretaudeau Anthony , Dikow Rebecca B. , Lemaitre Claire , Jouan Véronique , Ravallec Marc , Drezen Jean-Michel , Tagu Denis , Gyapay Gabor , Zhou Xin , Liu Shanlin , Webb Bruce A. , Brady Seán G. , Volkoff Anne-Nathalie
Published: December 2019

Polydnaviruses (PDVs) are mutualistic endogenous viruses associated with some lineages of parasitoid wasps that allow successful development of the wasps within their hosts. PDVs include two taxa resulting from independent virus acquisitions in braconid (bracoviruses) and ichneumonid wasps (ichnoviruses). PDV genomes are fully incorporated into the wasp genomes and comprise (1) virulence genes located on proviral segments that are packaged into the viral particle, and (2) genes involved in the production of the viral particles, which are not encapsidated. Whereas the genomic organization of bracoviruses within the wasp genome is relatively well known, the architecture of endogenous ichnoviruses remains poorly understood. We sequenced the genome of two ichnovirus-carrying wasp species,Hyposoter didymatorandCampoletis sonorensis. Complete assemblies with long scaffold sizes allowed identification of the integrated ichnovirus, highlighting an extreme dispersion within the wasp genomes of the viral loci,i.e.isolated proviral segments and clusters of replication genes. Comparing the two wasp species, proviral segments harbor distinct gene content and variable genomic environment, whereas viral machinery clusters show conserved gene content and order, and can be inserted in collinear wasp genomic regions. This distinct architecture is consistent with the biological properties of the two viral elements: proviral segments producing virulence proteins allowing parasitism success are fine-tuned to the host physiology, while an ancestral viral architecture was likely maintained for the genes involved in virus particle production. Finding a distinct genomic architecture of ichnoviruses and bracoviruses highlights different evolutionary trajectories leading to virus domestication in the two wasp lineages.
An Erg driven transcriptional program controls B-lymphopoiesis
Authors: Ng Ashley P. , Coughlan Hannah D. , Hediyeh-zadeh Soroor , Behrens Kira , Johanson Timothy M. , Yuan Low Michael Sze , Bell Charles C. , Gilan Omer , Chan Yih-Chih , Kueh Andrew J. , Boudier Thomas , DiRago Ladina , Hyland Craig D. , Ierino Helen , Mifsud Sandra , Viney Elizabeth , Willson Tracy , Dawson Mark A. , Allan Rhys S. , Herold Marco J. , Rogers Kelly , Tarlinton David M , Smyth Gordon K. , Davis Melissa J. , Nutt Stephen L. , Alexander Warren S.
Published: December 2019

Summary/Abstract

B-cell development is initiated by the stepwise differentiation of hematopoietic stem cells into lineage committed progenitors, ultimately generating the mature B-cells that mediate protective immunity. This highly regulated process also generates clonal immunological diversity via recombination of immunoglobulin genes. While several transcription factors that control B-cell development and V(D)J recombination have been defined, how these processes are initiated and coordinated into a precise regulatory network remains poorly understood. Here, we show that the transcription factor ETS Related Gene (Erg) is essential for the earliest steps in B-cell differentiation. Erg initiates a transcriptional network involving the B-cell lineage defining genes,Ebf1andPax5, that directly promotes the expression of key genes involved in V(D)J recombination and formation of the B-cell receptor. Complementation of the Erg-deficiency with a productively rearranged immunoglobulin gene rescued B-cell development, demonstrating that Erg is an essential and exquisitely stage specific regulator of the gene regulatory network controlling B-lymphopoiesis.
Self-supervised retinal thickness prediction enables deep learning from unlabeled data to boost classification of diabetic retinopathy
Authors: Holmberg Olle G. , Köhler Niklas D. , Martins Thiago , Siedlecki Jakob , Herold Tina , Keidel Leonie , Asani Ben , Schiefelbein Johannes , Priglinger Siegfried , Kortuem Karsten U. , Theis Fabian J.
Published: December 2019

Access to large, annotated samples represents a considerable challenge for training accurate deep-learning models in medical imaging. While current leading-edge transfer learning from pre-trained models can help with cases lacking data, it limits design choices, and generally results in the use of unnecessarily large models. We propose a novel, self-supervised training scheme for obtaining high-quality, pre-trained networks from unlabeled, cross-modal medical imaging data, which will allow for creating accurate and efficient models. We demonstrate this by accurately predicting optical coherence tomography (OCT)-based retinal thickness measurements from simple infrared (IR) fundus images. Subsequently, learned representations outperformed advanced classifiers on a separate diabetic retinopathy classification task in a scenario of scarce training data. Our cross-modal, three-staged scheme effectively replaced 26,343 diabetic retinopathy annotations with 1,009 semantic segmentations on OCT and reached the same classification accuracy using only 25% of fundus images, without any drawbacks, since OCT is not required for predictions. We expect this concept will also apply to other multimodal clinical data-imaging, health records, and genomics data, and be applicable to corresponding sample-starved learning problems.
Similar distribution of T-cell subsets in Crohn’s disease and in diverticulitis provide evidence against a primary causal role for these cells in Crohn’s
Authors: Akarca Ayse U , Ellery Peter , Segal Anthony W , Marafioti Teresa
Published: December 2019

Background and Aims

T lymphocytes are found in abnormally large numbers in the bowel in Crohn’s disease. This has led to the assumption by some that these cells play a causal role in the pathogenesis of what has been labelled an autoimmune disease. An alternative explanation for their presence is that, as part of the adaptive immune system, the accumulation of these cells is not a primary phenomenon, but is a secondary adaptive immune response to faecal material in the bowel wall. To distinguish between these two processes we compared the T-cell repertoire in the bowel in Crohn’s with that in diverticulitis, where the primary pathology is mechanical, with a subsequent immune response to the accumulated faecal material.

Methods

Six cases of Crohn’s disease and six patients with diverticulitis were studied. Dewaxed sections of bowel were stained with Anti-CD4, Anti-CD8, Anti-FOXP3 and Anti-CD25 to identify cytotoxic T-cells, NK-Tcells; T-helper and T-reg T-cells.

Results

No differences were found in the distribution of the different T-cell markers in either the mucosa or in areas of inflammation in the two conditions.

Conclusion

The accumulation of T-lymphocytes in the bowel in Crohn’s disease is likely to be a sign of an adaptive immune response to faecal material within the bowel rather than an indication of a primary causal immune attack on the bowel that produces the disease.
Improving reliability in clinical neuroimaging: a study in transgender persons
Authors: Khorashad Behzad Sorouri , Khazai Behnaz , Talaei Ali , Acar Freya , Hudson Anna R. , Borji Nahid , Saberi Hedieh , Aminzadeh Behzad , Mueller Sven C.
Published: December 2019

Although the neuroanatomy of transgender persons is slowly being charted, findings are presently discrepant. One important factor is the issue of power and low signal-to-noise (SNR) ratio in neuroimaging studies of rare study populations including endocrine or neurological patient groups. The present study assessed whether the reliability of findings across structural anatomical measures including thickness, volume, and surface area could be increased by using two back-to-back within session structural MRI scans in 40 transgender men (TM), 40 transgender women (TW), 30 cisgender men (CM), and 30 cisgender women (CW). Overall, findings in transgender persons were more consistent with at-birth assigned sex in brain volume and surface area while no group differences emerged for cortical thickness. Repeated measures analysis also indicated that having a second scan increased SNR in all ROIs, most notably bilateral frontal poles, accumbens nuclei and putamina. Furthermore, additional significant group differences emerged in cortical surface area when age and ICV were used as covariates. The results suggest that a simple time and cost effective measure to improve signal to noise ratio in rare clinical populations with low prevalence rates is a second anatomical scan when structural MRI is of interest.
Use of multi-flip angle measurements to account for transmit inhomogeneity and non-Gaussian diffusion in DW-SSFP
Authors: Tendler Benjamin C. , Foxley Sean , Hernandez-Fernandez Moises , Cottaar Michiel , Scott Connor , Ansorge Olaf , Miller Karla , Jbabdi Saad
Published: December 2019

Diffusion-weighted steady-state free precession (DW-SSFP) is an SNR-efficient diffusion imaging method. The improved SNR and resolution available at ultra-high field has motivated its use at 7T. However, these data tend to have severe B1 inhomogeneity, leading not only to spatially varying SNR, but also to spatially varying diffusivity estimates, confounding comparisons both between and within datasets. This study proposes the acquisition of DW-SSFP data at two-flip angles in combination with explicit modelling of non-Gaussian diffusion to address B1 inhomogeneity at 7T. DW-SSFP datasets were acquired from five fixed whole human post-mortem brains with a pair of flip angles that jointly optimize the diffusion contrast-to-noise across the brain. We compared one and two flip-angle DW-SSFP data using a diffusion tensor model that incorporates the full DW-SSFP Buxton signal model. The two-flip angle data were subsequently fitted using a modified DW-SSFP signal model that incorporates a Gamma distribution of diffusivities. This allowed us to generate tensor maps at a single, SNR-optimal effective b-value yielding more consistent SNR across tissue, in addition to eliminating the B1 dependence on diffusion coefficients and orientation maps. Our proposed approach will allow the use of DW-SSFP at 7T to derive diffusivity estimates that have greater interpretability, both within a single dataset and between experiments.

Highlights

B1 inhomogeneity at 7T leads to spatially varying SNR & ADC estimates in DW-SSFP

2-flip angle DW-SSFP data can address B1 effects in a cohort of post-mortem brains

Our approach reduces degradations in PDD estimates & improves whole brain coverage

Our approach provides a means to define ADCs at an SNR-optimal effective b-value
Signaling compartment at the ciliary tip is formed and maintained by intraflagellar transport and functions as sensitive salt detector
Authors: van der Burght Servaas N. , Rademakers Suzanne , Johnson Jacque-Lynne , Li Chunmei , Kremers Gert-Jan , Houtsmuller Adriaan B. , Leroux Michel R. , Jansen Gert
Published: December 2019

Primary cilia are ubiquitous antenna-like organelles that mediate cellular signaling and represent hotspots for human diseases termed ciliopathies. How signaling subcompartments are established within the microtubule-based organelle, and for example support Hedgehog or cGMP signal transduction pathways, remains a central question. Here we show that a C. elegans salt-sensing receptor type guanylate cyclase, GCY-22, accumulates at a high concentration within the distal region of the cilium. This receptor uses DAF-25 (Ankmy2 in mammals) to cross the transition zone (TZ) membrane diffusion barrier in the proximal-most region of the ciliary axoneme. Targeting of GCY-22 to the ciliary tip is dynamic, requiring the cargo-mobilizing intraflagellar transport (IFT) system. Disruption of transit across the TZ barrier or IFT trafficking causes GCY-22 protein mislocalization and defects in the formation, maintenance, and function of the ciliary tip compartment required for chemotaxis to low NaCl concentrations. Together, our findings reveal how a previously undescribed cilium tip cGMP signaling compartment is established and contributes to the physiological function of a primary cilium.
Neural Encoding for Human Visual Cortex with Deep Neural Networks Learning “What” and “Where”
Authors: Wang Haibao , Huang Lijie , Du Changde , Li Dan , Wang Bo , He Huiguang
Published: December 2019

Neural encoding, a crucial aspect to understand human brain information processing system, aims to establish a quantitative relationship between the stimuli and the evoked brain activities. In the field of visual neuroscience, with the ability to explain how neurons in primary visual cortex work, population receptive field (pRF) models have enjoyed high popularity and made reliable progress in recent years. However, existing models rely on either the inflexible prior assumptions about pRF or the clumsy parameter estimation methods, severely limiting the expressiveness and interpretability. In this paper, we propose a novel neural encoding framework by learning “what” and “where” with deep neural networks. The modeling approach involves two separate aspects: the spatial characteristic (“where”) and feature selection (“what”) of neuron populations in visual cortex. Specifically, we use the receptive field estimation and multiple features regression to learn these two aspects respectively, which are implemented simultaneously in a deep neural network. The two forms of regularizations: sparsity and smoothness, are also adopted in our modeling approach, so that the receptive field can be estimated automatically without prior assumptions about shapes. Furthermore, an attempt is made to extend the voxel-wise modeling approach to multi-voxel joint encoding models, and we show that it is conducive to rescuing voxels with poor signal-to-noise characteristics. Extensive empirical results demonstrate that the method developed herein provides an effective strategy to establish neural encoding for human visual cortex, with the weaker prior constraints but the higher encoding performance.

Author summary

Characterizing the quantitative relationship between the stimuli and the evoked brain activities usually involves learning the spatial characteristic (“where”) and feature selection (“what”) of neuron populations. As an effective strategy, we propose a novel end-to-end “what” and “where” architecture to perform neural encoding. The proposed modeling approach consists of receptive field estimation and multiple features regression, which learns “where” and “what” simultaneously in a deep neural network. Different from previous methods, we use the sparsity and smoothness regularizations in the deep neural network to guide the receptive field estimation, so that the receptive field for each voxel can be estimated automatically. Moreover, in consideration of computational similarities between adjacent voxels, we made an attempt to extend the proposed modeling approach to multi-voxel joint encoding models, improving the encoding performance of voxels with poor signal-to-noise characteristics. Empirical evaluations show that the proposed method outperforms other baselines to achieve the state-of-the-art performance.
Two-variable nullcline analysis of ionic general equilibrium predicts calcium homeostasis in ventricular myocytes
Authors: Conesa David , Echebarria Blas , Peñaranda Angelina , Cantalapiedra Inmaculada R. , Shiferaw Yohannes , Alvarez-Lacalle Enrique
Published: December 2019

Ventricular contraction is roughly proportional to the amount of calcium released from the Sarcoplasmic Reticulum (SR) during systole. While it is rather straightforward to measure calcium levels and contractibility under different physiological condition, the complexity of calcium handling during systole and diastole has made the prediction of its release at steady state impossible. Here we approach the problem analyzing the evolution of intracellular and extracellular calcium fluxes during a single beat which is away from homeostatic balance. Using an in-silico subcellular model of rabbit ventricular myocyte, we show that the high dimensional nonlinear problem of finding the steady state can be reduced to a two-variable general equilibrium condition where pre-systolic calcium level in the cytosol and in the SR must fulfill simultaneously two different equalities. This renders calcium homeostasis as a problem that can be studied in terms of its equilibrium structure, leading to precise predictions of steady state from single-beat measurements. We show how changes in ionic channels modify the general equilibrium as shocks would do in general equilibrium macroeconomic models. This allows us to predict when an enhanced entrance of calcium in the cell reduces its contractibility and explain why SERCA gene therapy, a change in calcium handling to treat heart failure, might fail to improve contraction even when it successfully increases SERCA expression.

Author summary

Cardiomyocytes, upon voltage excitation, release calcium, which leads to cell contraction. However, under some pathological conditions, calcium handling is impaired. Recently, SERCA gene therapy, whose aim is to improve Ca2+ sequestration by the Sarcoplasmic Reticulum (SR), has failed to improve the prognosis of patients with Heart Failure. This, together with recent counterintuitive results in calcium handling, has highlighted the need for a framework to understand calcium homeostasis across species and pathologies. We show here that the proper framework is a general equilibrium approach of two independent variables. The development of this framework allows us to find a possible mechanism for the failure of SERCA gene therapy even when it manages to increase Ca SERCA expression.
The association of self-reported sleep quality and obesity in Kuwait using the Pittsburgh Sleep Quality Index (PSQI)
Authors: Alghaith Abdulwahab , Azim Rafaat , Ahmad Rasheed , Al-Rashed Fatema
Published: December 2019

Obesity is an epidemic problem facing Kuwait and other neighboring countries within the region. Lifestyle and social structure in this region differ in comparison to the western world. The hot chalinging climate favor night time activities while working hours still force a stringent early attendence. This study is specifically conducted for Kuwait’s population to investigate the link between Sleep Quality (SQ) and obesity. A cross-sectional study was conducted for a sample of 1002 participants. Structured questionnaires were used in the study as a tool of research. The participants were asked about their sleep habits, sleep problems, medications, job nature and demographics. All participants consented prior to conducting the survey. In order to measure sleep quality (SQ), the Pittsburgh Sleep Quality Index (PQSI) was used. Statistical analysis was conducted between variables and the data were compared using either two-tailed t-test or one-way ANOVA followed by Tukeys multiple comparison test. Pearson’s correlation coefficient ‘r’ was used to assess linear dependence. 59.4% of Kuwait population reported a PSQI score higher than 5, with 57.3% of the participants reporting less than 6 hours of sleep per day. The presented data shows that both sleep quality and sleep duration are considered inadequate in comparison to international sleep quality standards. None the less, we also found strong a significant association between sleep quality and its component and obesity, while other factors such as age and gender were found insignificant. These finding suggest that sleep deprivation and disturbance could be an indirect inducing factor of obesity in Kuwait. The researchers are of the view that there is a need for more study in the area of obesity and SQ in order to handle the obesity epidemic in the country.
Muscle Mitochondrial Capacity and Endurance in Adults with Type 1 Diabetes
Authors: Hewgley Riley A. , Moore Bethany T. , Willingham T. Bradley , Jenkins Nathan T. , McCully Kevin K.
Published: December 2019

The impact of type 1 diabetes (T1D) on muscle endurance and oxidative capacity is currently unknown.

Purpose

Measure muscle endurance and oxidative capacity of adults with T1D compared to controls.

Methods

A cross-sectional study design with a control group was used. Subjects (19-37 years old) with T1D (n=17) and controls (n=17) were assessed with hemoglobin A1c (HbA1c) and casual glucose. Muscle endurance was measured with an accelerometer at stimulation frequencies of 2, 4, and 6 Hz for a total of nine minutes. Mitochondrial capacity was measured using near-infrared spectroscopy after exercise as the rate constant of the rate of recovery of oxygen consumption.

Results

T1D and control groups were similar in age, sex, height, and race. The T1D group had slightly higher BMI values and adipose tissue thickness over the forearm muscles. Casual glucose was 150±70 mg/dL for T1D and 98±16 mg/dL for controls (P=0.006). HbA1c of T1D subjects was 7.1±0.9% and 5.0±0.4% for controls (P<0.01). Endurance indexes at 2, 4, and 6 Hz were 94.5±5.2%, 81.8±8.4%, and 68.6±13.5% for T1D and 94.6±4.1%, 85.9±6.3%, and 68.7±15.4% for controls (p = 0.97, 0.12, 0.99, respectively). There were no differences between groups in mitochondrial capacity (T1D= 1.9±0.5 min−1 and control=1.8±0.4 min−1, P=0.29) or reperfusion rate (T1D= 8.8±2.8s and control=10.3±3.0s, P=0.88). There were no significant correlations between HbA1c and either muscle endurance, mitochondrial capacity or reperfusion rate.

Conclusions

Adults with T1D did not have reduced oxidative capacity, muscle endurance or muscle reperfusion rates compared to controls. HbA1c also did not correlate with muscle endurance, mitochondrial capacity or reperfusion rates. Future studies should extend these measurements to older people or people with poorly-controlled T1D.
Effects of host plants nutrient on the nutrient in Bradysia cellarum and Bradysia impatiens
Authors: Gou Yuping , Quandahor Peter , Zhang Yanxia , Liu Changzhong
Published: December 2019

The chive maggots Bradysia cellarum the fungus gnats Bradysia impatiens are two main root pests of plants. They can coexist on same host plants and have become devastating pests on liliaceous crops and edible fungi. Their growth and development are affected by nutrients of their host plants. We studied the effects of different host plant nutrients on the nutrient contents of these two Bradysia species. We assayed the nutrients in the roots of chive, board bean (B-bean), lettuce, cabbage, wild cabbage (W-cabbage) and pepper, and analysed the nutrient content of the two Bradysia species after three continuous generations of feeding on these different host plants. There chive and B-bean had higher contents of protein, free amino acid and starch than in other host plants. Soluble sugar, fat and protein contents were significantly higher in both Bradysia species when they were reared on chive and B-bean than when reared on cabbage, lettuce, W-cabbage and pepper. Our study provides a reference for further studies on the host range of the two Bradysia species, as well as knowledge for consideration in field crop rotations.
The geometry and genetics of hybridization
Authors: Schneemann Hilde , De Sanctis Bianca , Roze Denis , Bierne Nicolas , Welch John J.
Published: December 2019

We develop an analytical framework for predicting the fitness of hybrid genotypes, based on Fisher’s geometric model. We first show that all of the model parameters have a simple geometrical and biological interpretation. Hybrid fitness decomposes into intrinsic effects of hybridity and heterozygosity, and extrinsic measures of the (local) adaptedness of the parental lines; and all of these correspond to distances in a phenotypic space. We also show how these quantities change over the course of divergence, with convergence to a characteristic pattern of intrinsic isolation. Using individual-based simulations, we then show that the predictions apply to a wide range of population genetic regimes, and divergence conditions, including allopatry and parapatry, local adaptation and drift. We next connect our results to the quantitative genetics of line crosses in variable or patchy environments. This relates the geometrical distances to quantities that can be estimated from cross data, and provides a simple interpretation of the “composite effects” in the quantitative genetics partition. Finally, we develop extensions to the model, involving selectively-induced disequilibria, and variable phenotypic dominance. The geometry of fitness landscapes provides a unifying framework for understanding speciation, and wider patterns of hybrid fitness.
AlphaBeta: Computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants
Authors: Shahryary Yadollah , Symeonidi Aikaterini , Hazarika Rashmi R. , Denkena Johanna , Mubeen Talha , Hofmeister Brigitte , van Gurp Thomas , Colomé-Tatché Maria , Verhoeven Koen , Tuskan Gerald , Schmitz Robert J , Johannes Frank
Published: December 2019

Introduction

Heritable changes in cytosine methylation can arise stochastically in plant genomes independently of DNA sequence alterations. These so-called ‘spontaneous epimutations’ appear to be a byproduct of imperfect DNA methylation maintenance during mitotic or meitotic cell divisions. Accurate estimates of the rate and spectrum of these stochastic events are necessary to be able to quantify how epimutational processes shape methylome diversity in the context of plant evolution, development and aging.

Method

Here we describe AlphaBeta, a computational method for estimating epimutation rates and spectra from pedigree-based high-throughput DNA methylation data. The approach requires that the topology of the pedigree is known, which is typically the case in the experimental construction of mutation accumulation lines (MA-lines) in sexually or clonally reproducing species. However, this method also works for inferring somatic epimutation rates in long-lived perennials, such as trees, using leaf methylomes and coring data as input. In this case, we treat the tree branching structure as an intra-organismal phylogeny of somatic lineages and leverage information about the epimutational history of each branch.

Results

To illustrate the method, we applied AlphaBeta to multi-generational data from selfing- and asexually-derived MA-lines in Arabidopsis and dandelion, as well as to intra-generational leaf methylome data of a single poplar tree. Our results show that the epimutation landscape in plants is deeply conserved across angiosperm species, and that heritable epimutations originate mainly during somatic development, rather than from DNA methylation reinforcement errors during sexual reproduction. Finally, we also provide the first evidence that DNA methylation data, in conjunction with statistical epimutation models, can be used as a molecular clock for age-dating trees.

Conclusion

AlphaBeta faciliates unprecedented quantitative insights into epimutational processes in a wide range of plant systems. Software implementing our method is available as a Bioconductor R package at http://bioconductor.org/packages/3.10/bioc/html/AlphaBeta.html
Disrupting female flight in the vectorAedes aegypti
Authors: O’Leary Sarah , Adelman Zach N.
Published: December 2019

Aedes aegyptiis a vector of dengue, chikungunya, and Zika viruses. Current vector control strategies such as community engagement, source reduction, and insecticides have not been sufficient to prevent viral outbreaks. Thus, interest in novel strategies involving genetic engineering is growing. Female mosquitoes rely on flight to mate with males and obtain a bloodmeal from a host. We hypothesized that knockout of genes specifically expressed in female mosquitoes associated with the indirect flight muscles would result in a flightless female mosquito. With the CRISPR-Cas9 system, we performed embryonic microinjections of Cas9 protein and guide RNAs specific to genes hypothesized to control flight in mosquitoes, and have obtained genetic knockouts in several genes specifically expressed in the flight-muscle, including those specific to female flight muscle. Analysis of the phenotype of these female-specific gene knockout mutants resulted in flightless females and flying males. While further assessment is required, this work lays the groundwork for a mechanism of population control that is female-specific for theAe. aegyptivector.