bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21
Authors: Mukhopadhyay Nandita , Bishop Madison , Mortillo Michael , Chopra Pankaj , Hetmanski Jacqueline B. , Taub Margaret A. , Moreno Lina M. , Valencia-Ramirez Luz Consuelo , Restrepo Claudia , Wehby George L. , Hecht Jacqueline T. , Deleyiannis Frederic , Butali Azeez , Weinberg Seth M. , Beaty Terri H. , Murray Jeffrey C. , Leslie Elizabeth J. , Feingold Eleanor , Marazita Mary L.
Published: August 2019

Orofacial clefts (OFCs) are one of the most common birth defects worldwide and create a significant health burden. The majority of OFCs are non-syndromic, and the genetic component has been only partially determined. Here, we analyze whole genome sequence (WGS) data for association with risk of OFCs in European and Colombian families selected from a multicenter family-based OFC study. Part of the Gabriella Miller Kids First Pediatric Research Program, this is the first large-scale WGS study of OFC in parent-offspring trios. WGS provides deeper and more specific genetic data than currently available using imputation on single nucleotide polymorphic (SNP) marker panels. Here, association analysis of genome-wide single nucleotide variants (SNV) and short insertions and deletions (indels) identified a new locus on chromosome 21 in Colombian families, within a region known to be expressed during craniofacial development. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, and the need for larger samples when for studying OFCs and other birth defects in admixed populations.
An MRI-Derived Neuroanatomical Atlas of the Fischer 344 Rat Brain
Authors: Goerzen Dana , Fowler Caitlin , Devenyi Gabriel A. , Germann Jurgen , Madularu Dan , Mallar Chakravarty M. , Near Jamie
Published: August 2019

This paper reports the development of a high-resolution 3-D MRI atlas of the Fischer 344 adult rat brain. The atlas is a 60 μm isotropic image volume composed of 256 coronal slices with 71 manually delineated structures and substructures. The atlas was developed using Pydpiper image registration pipeline to create an average brain image of 41 four-month-old male and female Fischer 344 rats. Slices in the average brain image were then manually segmented, individually and bilaterally, on the basis of image contrast in conjunction with Paxinos and Watson’s (2007) stereotaxic rat brain atlas. Summary statistics (mean and standard deviation of regional volumes) are reported for each brain region across the sample used to generate the atlas, and a statistical comparison of a chosen subset of regional brain volumes between male and female rats is presented. On average, the coefficient of variation of regional brain volumes across all rats in our sample was 4%, with no individual brain region having a coefficient of variation greater than 13%. A full description of methods used, as well as the atlas, the template that the atlas was derived from, and a masking file, can be found at Zenodo at https://doi.org/10.5281/zenodo.3555556. To our knowledge, this is the first MRI atlas created using Fischer 344 rats and will thus provide an appropriate neuroanatomical model for researchers working with this strain.

HIGHLIGHTS

⍰ Open-access high-resolution anatomical MRI template for Fischer 344 rat brain.

⍰ Segmented atlas of 71 regions for use as a tool in Fischer 344 preclinical research paradigms.

⍰ Analysis of population variability of regional brain volumes.

⍰ Analysis of sex-differences in regional brain volumes

KEYWORDS: Fischer 344; Structural MRI; Segmentation; Rat brain template; Digital brain atlas; Sex-differences;
Mechanical feedback and robustness of apical constrictions inDrosophilaembryo ventral furrow formation
Authors: Holcomb Michael C. , Gao Guo-Jie Jason , Servati Mahsa , Schneider Dylan , McNeely Presley K. , Thomas Jeffrey H. , Blawzdziewicz Jerzy
Published: August 2019

Formation of the ventral furrow in theDrosophilaembryo relies on the apical constriction of cells in the ventral region to produce bending forces that drive tissue invagination. Recently [J Phys Condens Matter. 2016;28(41):414021], we observed that apical constrictions during the initial phase of ventral furrow formation produce elongated patterns of cellular constriction chains prior to invagination, and argued that these are indicative of tensile stress feedback. Here, we quantitatively analyze the constriction patterns preceding ventral furrow formation and find that they are consistent with the predictions of our active-granular-fluid model of a monolayer of mechanically coupled stress-sensitive constricting particles. Our model shows that tensile feedback causes constriction chains to develop along underlying precursor tensile stress chains that gradually strengthen with subsequent cellular constrictions. As seen in both our model and available optogenetic experiments, this mechanism allows constriction chains to penetrate or circumvent zones of reduced cell contractility, thus increasing the robustness of ventral furrow formation to spatial variation of cell contractility by rescuing cellular constrictions in the disrupted regions.
Multiple protein-DNA interfaces unravelled by evolutionary information, physico-chemical and geometrical properties
Authors: Corsi F. , Lavery R. , Laine E. , Carbone A.
Published: August 2019

The usage made of protein surfaces by nucleic acids still remains largely unknown, due to the lack of available structural data and the inherent complexity associated to protein surface deformability and evolution. In this work, we present a method that contributes to decipher such complexity by predicting protein-DNA interfaces and characterizing their properties. It relies on three biologically and physically meaningful descriptors, namely evolutionary conservation, physico-chemical properties and surface geometry. We carefully assessed its performance on several hundreds of protein structures. We achieve a higher sensitivity compared to state-of-the-art methods, and similar precision. Importantly, we show that our method is able to unravel ‘hidden’ binding sites by applying it to unbound protein structures and to proteins binding to DNA via multiple sites and in different conformations. It is implemented as a fully automated tool, , freely accessible at: http://www.lcqb.upmc.fr/JET2DNA. We also provide a new reference dataset of 187 protein-DNA complex structures, representative of all types of protein-DNA interactions, along with a subset of associated unbound structures: http://www.lcqb.upmc.fr/PDNAbenchmarks.
Deep Learning Strategies for Differential Expansion Microscopy
Authors: Gatti Domenico L. , Arslanturk Suzan , Lal Sinan , Jena Bhanu P.
Published: August 2019

Differential expansion microscopy (DiExM) achieves greater than 500-fold volumetric expansion of biological specimens without loss of cellular antigens. The anisotropic character of this expansion, which affects tissues, cells, organelles and even sub-organelle features, requires the application of novel machine learning approaches to extract accurate and meaningful morphological and biochemical information from DiExM images. Here we describe current strategies to achieve this goal.
Detecting brain network communities: considering the role of information flow and its different temporal scales
Authors: Sanchez-Rodriguez Lazaro M. , Iturria-Medina Yasser , Mouches Pauline , Sotero Roberto C.
Published: August 2019

The identification of community structure in graphs continues to attract great interest in several fields. Network neuroscience is particularly concerned with this problem considering the key roles communities play in brain processes and functionality. Most methods used for community detection in brain graphs are based on the maximization of a parameter-dependent modularity function that often obscures the physical meaning and hierarchical organization of the partitions of network nodes. In this work, we present a new method able to detect communities at different scales in a natural, unrestricted way. First, to obtain an estimation of the information flow in the network we release random walkers to freely move over it. The activity of the walkers is separated into oscillatory modes by using empirical mode decomposition. After grouping nodes by their co-occurrence at each time scale,k-modes clustering returns the desired partitions. Our algorithm was first tested on benchmark graphs with favorable performance. Next, it was applied to real and simulated anatomical and/or functional connectomes in the macaque and human brains. We found a clear hierarchical repertoire of community structures in both the anatomical and the functional networks. The observed partitions range from the evident division in two hemispheres –in which all processes are managed globally– to specialized communities seemingly shaped by physical proximity and shared function. Our results stimulate the research of hierarchical community organization in terms of temporal scales of information flow in the brain network.

Highlights

- Oscillatory modes of networks’ signals carry information on architectural rules.

- Meaningful partitions of the brain networks are found over different temporal scales.

- The multiscale organization of the brain responds to the function of its components.
The domain-general multiple demand (MD) network does not support core aspects of language comprehension: a large-scale fMRI investigation
Authors: Diachek Evgeniia , Blank Idan , Siegelman Matthew , Affourtit Josef , Fedorenko Evelina
Published: August 2019

Aside from the language-selective left-lateralized fronto-temporal network, language comprehension sometimes additionally recruits a domain-general bilateral fronto-parietal network implicated in executive functions: the multiple demand (MD) network. However, the nature of the MD network’s contributions to language comprehension remains debated. To illuminate the role of this network in language processing, we conducted a large-scale fMRI investigation using data from 30 diverse word and sentence comprehension experiments (481 unique participants, 678 scanning sessions). In line with prior findings, the MD network was active during many language tasks. Moreover, similar to the language-selective network, which is robustly lateralized to the left hemisphere, these responses were stronger in the left-hemisphere MD regions. However, in stark contrast with the language-selective network, the MD network responded more strongly (i) to lists of unconnected words than to sentences, and critically, (ii) in paradigms with an explicit task compared to passive comprehension paradigms. In fact, many passive comprehension tasks failed to elicit a response above the fixation baseline in the MD network, in contrast to strong responses in the language-selective network. In tandem, these results argue against a role for the MD network in core aspects of sentence comprehension like inhibiting irrelevant meanings or parses, keeping intermediate representations active in working memory, or predicting upcoming words or structures. These results align with recent evidence of relatively poor tracking of the linguistic signal by the MD regions during naturalistic comprehension, and instead suggest that the MD network’s engagement during language processing likely reflects effort associated with extraneous task demands.

Significance Statement

Domain-general executive processes, like working memory and cognitive control, have long been implicated in language comprehension, including in neuroimaging studies that have reported activation in domain-general multiple demand (MD) regions for linguistic manipulations. However, much prior evidence has come from paradigms where language interpretation is accompanied by extraneous tasks. Using a large fMRI dataset (30 experiments/481 participants/678 sessions), we demonstrate that MD regions are engaged during language comprehension in the presence of task demands, but not during passive reading/listening—conditions that strongly activate the fronto-temporal language network. These results present a fundamental challenge to proposals whereby linguistic computations, like inhibiting irrelevant meanings, keeping representations active in working memory, or predicting upcoming elements, draw on domain-general executive resources.
Failure to clear developmental apoptosis contributes to the pathology of RNASET2-deficient leukoencephalopathy
Authors: Hamilton Noémie , Rutherford Holly A. , Isles Hannah M. , Petts Jessica J. , Weber Thomas , Henneke Marco , Gärtner Jutta , Dunning Mark , Renshaw Stephen A.
Published: August 2019

The contribution of microglia in neurological disorders is emerging as a leading driver rather than a consequence of pathology. RNAseT2-deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimics a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to an immune response suggest an inflammatory and embryonic origin of the pathology. In this study, we identify deficient microglia as an early marker of pathology. Using theex uterodevelopment and the optical transparency of anrnaset2-deficient zebrafish model, we found that dysfunctional microglia fail to clear apoptotic neurons during brain development. This was associated with increased number of apoptotic cells and behavioural defects lasting into adulthood. This zebrafish model recapitulates all aspect of the human disease to be used as a robust preclinical model. Using microglia-specific depletion and rescue experiments, we identified microglia as potential drivers of the pathology and highlight tissue-specific approaches as future therapeutic avenues.
Mitochondrial DNA variation of Leber’s Hereditary Optic Neuropathy (LHON) in Western Siberia
Authors: Starikovskaya E.B. , Shalaurova S.A. , Dryomov S.V. , Nazhmidenova A.M. , Volodko N.V. , Bychkov I.Y. , Mazunin I.O. , Sukernik R.I.
Published: August 2019

Leber’s hereditary optic neuropathy (LHON) is a form of disorder caused by pathogenic mutations in a mitochondrial DNA. LHON is maternally inherited disease, which manifests mainly in young adults, affecting predominantly males. Clinically LHON has a manifestation as painless central vision loss, resulting in early onset of disability. Epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients in the Western Siberia population. Known “primary” pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53,10% (17/32), m.3460G>A – 21,90% (7/32), m.14484T>C – 18,75% (6/32), and rare m.10663T>C and m.3635G>A represent 6,25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.9444C>T, m.6261G>A, m.9921G>A, m.8551T>C, m.8412T>C, m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.
Comprehensive longitudinal study of epigenetic mutations in aging
Authors: Wang Yunzhang , Karlsson Robert , Jylhävä Juulia , Hedman Åsa K. , Almqvist Catarina , Karlsson Ida K. , Pedersen Nancy L. , Almgren Malin , Hägg Sara
Published: August 2019

Background

The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.

Results

We verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.

Conclusions

Here we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.
Expression atlas of Selaginella moellendorffii provides insights into the evolution of vasculature, secondary metabolism and roots
Authors: Ferrari Camilla , Shivhare Devendra , Hansen Bjoern Oest , Winter Nikola , Pasha Asher , Esteban Eddi , Provart Nicholas J. , Kragler Friedrich , Fernie Alisdair , Tohge Takayuki , Mutwil Marek
Published: August 2019

The lycophyte Selaginella moellendorffii represents early vascular plants and is studied to understand the evolution of higher plant traits such as the vasculature, leaves, stems, roots, and secondary metabolism. However, little is known about the gene expression and transcriptional coordination of Selaginella genes, which precludes us from understanding the evolution of transcriptional programs behind these traits.

We here present a gene expression atlas comprising all major organs, tissue types, and the diurnal gene expression profiles for S. moellendorffii. The atlas is part of the CoNekT-Plants database (conekt.plant.tools), which enables comparative transcriptomic analyses across two algae and seven land plants.

We show that the transcriptional gene module responsible for the biosynthesis of lignocellulose evolved in the ancestor of vascular plants, and pinpoint the duplication and subfunctionalization events that generated multiple gene modules involved in the biosynthesis of various cell wall types. We further demonstrate how secondary metabolism is transcriptionally coordinated and integrated with other cellular pathways. Finally, we identify root-specific genes in vascular plants and show that the evolution of roots did not coincide with an increased appearance of gene families, suggesting that the existing genetic material was sufficient to generate new organs.

Our updated database at conekt.plant.tools provides a unique resource to study the evolution of genes, gene families, transcriptomes, and functional gene modules in the Archaeplastida kingdom.
Performance evaluation of a new custom, multi-component DNA isolation method optimized for use in shotgun metagenomic sequencing-based aerosol microbiome research
Authors: Bøifot Kari Oline , Gohli Jostein , Moen Line Victoria , Dybwad Marius
Published: August 2019

Background

Aerosol microbiome research advances our understanding of bioaerosols, including how airborne microorganisms affect our health and surrounding environment. Traditional microbiological/molecular methods are commonly used to study bioaerosols, but do not allow for generic, unbiased microbiome profiling. Recent studies have adopted shotgun metagenomic sequencing (SMS) to address this issue. However, SMS requires relatively large DNA inputs, which are challenging when studying low biomass air environments, and puts high requirements on air sampling, sample processing and DNA isolation protocols. Previous SMS studies have consequently adopted various mitigation strategies, including long-duration sampling, sample pooling, and whole genome amplification, each associated with some inherent drawbacks/limitations.

Results

Here, we demonstrate a new custom, multi-component DNA isolation method optimized for SMS-based aerosol microbiome research. The method achieves improved DNA yields from filter-collected air samples by isolating DNA from the entire filter extract, and ensures unbiased microbiome representation by combining chemical, enzymatic and mechanical lysis. Benchmarking against two state-of-the-art DNA isolation methods was performed with a mock microbial community and real-world subway air samples. All methods demonstrated similar performance regarding DNA yield and community representation with the mock community. However, with subway air samples, the new method obtained drastically improved DNA yields, while SMS revealed that the new method reported higher diversity and gave better taxonomic coverage. The new method involves intermediate filter extract separation into a pellet and supernatant fraction. Using subway air samples, we demonstrate that supernatant inclusion results in improved DNA yields. Furthermore, SMS of pellet and supernatant fractions revealed overall similar taxonomic composition but also identified differences that could bias the microbiome profile, emphasizing the importance of processing the entire filter extract.

Conclusions

By demonstrating and benchmarking a new DNA isolation method optimized for SMS-based aerosol microbiome research with both a mock microbial community and real-world air samples, this study contributes to improved selection, harmonization, and standardization of DNA isolation methods. Our findings highlight the importance of ensuring end-to-end sample integrity and using methods with well-defined performance characteristics. Taken together, the demonstrated performance characteristics suggest the new method could be used to improve the quality of SMS-based aerosol microbiome research in low biomass air environments.
Single-cell molecular and cellular architecture of the mouse neurohypophysis
Authors: Chen Qiyu , Leshkowitz Dena , Blechman Janna , Levkowitz Gil
Published: August 2019

The neurohypophysis (NH), located at the posterior lobe of the pituitary, is a major neuroendocrine tissue, which mediates osmotic balance, blood pressure, reproduction, and lactation by means of releasing the neurohormones oxytocin and arginine-vasopressin from the brain into the peripheral blood circulation. The major cellular components of the NH are hypothalamic axonal termini, fenestrated endothelia and pituicytes, the resident astroglia. However, despite the physiological importance of the NH, the exact molecular signature defining neurohypophyseal cell types and in particular the pituicytes, remains unclear. Using single cell RNA sequencing, we captured seven distinct cell types in the NH and intermediate lobe (IL) of adult male mouse. We revealed novel pituicyte markers showing higher specificity than previously reported. Single moleculein situhybridization revealed spatial organization of the major cell types implying intercellular communications. We present a comprehensive molecular and cellular characterization of neurohypophyseal cell-types serving as a valuable resource for further functional research.

Significance Statement

The neurohypophysis (NH) is a major neuroendocrine interface, which allows the brain to regulate the function of peripheral organs in response to specific physiological demands. Despite its importance, a comprehensive molecular description of cell identities in the NH is still lacking. Utilizing single cell RNA sequencing technology, we identified the transcriptomes of five major neurohypophyseal cell types in the adult male mice and mapped the spatial distribution of selected cell typesin situ. We revealed an unexpected cellular heterogeneity of the neurohypophysis and provide novel molecular markers for neurohypophyseal cell types with higher specificity than previously reported.
The use of ATR-FTIR spectroscopy to characterise crude heparin samples by composition and structural features
Authors: Devlin Anthony , Mauri Lucio , Guerrini Marco , Yates Edwin A. , Skidmore Mark A.
Published: August 2019

Production of the major anticoagulant drug, heparin, is a complex process that begins with the collection of crude material from a dispersed network of suppliers with poor traceability, an issue that was made apparent in 2007-2008, when batches of heparin were contaminated deliberately in the supply chain, resulting in over 100 deaths in the US alone. Several analytical techniques are used currently for the characterisation of pharmaceutical grade heparin, but few have been applied to its crude counterpart. One exception is NMR spectroscopy which was used to study crude heparin (2017), however, owing to the high set-up and running costs, as well as the need for skilled technical operators, the use of NMR at crude heparin production plants is unviable. An alternative, practical, spectroscopic method is attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) that is user-friendly, economical and, importantly, requires little specialised training or sample preparation. Using a top-down chemometric approach employing principal component analysis, ATR-FTIR spectroscopy was able to distinguish crude heparins based on their similarity to pharmaceutical heparin, as well as on their compositional and structural features, which included levels of sulphation, the extent of related conformational changes, as well as the quantities of chondroitin and dermatan sulphate present. This approach lends itself to automation and will enable users and regulators to undertake quality control of crude heparin during manufacture. The method requires only economical, portable equipment and little specialised training, bringing the high-quality analysis of crude heparin within reach of both manufacturers and regulators for the first time.
Modeling the relationship between estimated foliar fungicide use and soybean yield losses due to foliar fungal diseases in the United States
Authors: Bandara Ananda Y. , Weerasooriya Dilooshi K. , Conley Shawn P. , Bradley Carl A. , Allen Tom W. , Esker Paul D.
Published: August 2019

Fungicide use in the United States to manage soybean diseases has increased in recent years. The ability of fungicides to reduce disease-associated yield losses varies greatly depending on multiple factors. Nonetheless, historical data are useful to understand the broad sense and long-term trends related to fungicide use practices. In the current study, the relationship between estimated soybean yield losses due to selected foliar diseases and foliar fungicide use was investigated using annual data from 28 soybean growing states over the period of 2005 to 2015. At a national scale, a significant quadratic relationship was observed between total estimated yield losses and total fungicide use (R2 = 0.123, P < 0.0001) where yield losses initially increased, reached a plateau, and subsequently decreased with increasing fungicide use. The positive phase of the quadratic curve could be associated with insufficient amount of fungicides being used to manage targeted diseases, application of more-than-recommended prophylactic fungicides under no/low disease pressure, application of curative fungicides after economic injury level, and reduced fungicide efficacy due to a variety of factors such as unfavorable environmental conditions and resistance of targeted pathogen populations to the specific active ingredient applied. Interestingly, a significant quadratic relationship was also observed between total soybean production and total foliar fungicide use (R2= 0.36, P < 0.0001). The positive phase of the quadratic curve may suggest that factors like plant physiological changes, including increased chlorophyll content, photosynthetic rates, water use efficiency, and delayed senescence that have been widely reported to occur after application of certain foliar fungicides could have potentially contributed to enhanced yield. Therefore, the current study provides evidence of the potential usefulness of foliar fungicide applications to mitigate soybean yield losses associated with foliar diseases and their potential to positively impact soybean production/yield at national and regional scales although discrepancies to the general trends observed at national and regional scales do prevail at the local (state) level.
The impact of biological invasion and genomic local adaptation on the geographical distribution of Aedes aegypti in Panama
Authors: Bennett Kelly L. , McMillan W. Owen , Loaiza. Jose R.
Published: August 2019

Local adaptation is an important consideration when predicting arthropod-borne disease risk because it can impact on vector population fitness and persistence. However, the extent that vector populations are adapted to local environmental conditions and whether this can impact on species distributions generally remains unknown. Here we find that the geographic distribution of Ae. aegypti across Panama is rapidly changing as a consequence of the recent invasion by its ecological competitor, Aedes albopictus. Although Ae. albopictus has displaced Ae. aegypti in some areas, species coexist across many areas, raising the question: What biological and environmental factors permit population persistence?. Despite low population structure and high gene flow in Ae. aegypti across Panama, excepting the province of Bocas del Toro, we identify 128 candidate SNPs, clustered within 17 genes, which show a strong genetic signal of local adaptation. This putatively adaptive variation occurs across relatively fine geographic scales with the composition and frequency of candidate adaptive loci differing between populations in wet tropical environments along the Caribbean coast and the dry tropical conditions typical of the Pacific coast of Panama. Temperature and vegetation were important predictors of adaptive genomic variation in Ae. aegypti with potential areas of local adaptation occurring within the Caribbean region of Bocas del Toro, the Pacific coastal areas of Herrera and Panama City and the eastern Azuero Peninsula. Interestingly, several of these locations coincide with areas where Ae. aegypti and Ae. albopictus co-exist, suggesting that Ae. aegypti could have an adaptive edge under local environmental conditions that impacts on inter-specific competition with Ae. albopictus. Our results guide future experimental work by suggesting that locally adapted Ae. aegypti are able to persist on invasion by Ae. albopictus and, as a consequence, may fundamentally alter future arborviral disease risk and efforts to control mosquito populations.

Author Summary

Local environmental adaptation of mosquito vectors can alter the landscape of arthropod-borne disease by impacting on life history traits that increase their relative fitness thus promoting population persistence. We have identified a number of genomic loci in Ae. aegypti from Panama that exhibit a signal of natural selection associated with variation in the environment. Loci with a signal of local adaptation are predominately partitioned between wet and dry tropical environments with variation largely impacted by temperature and vegetation indices. Local adaptation in tandem with changes in the geographic distribution of Ae. aegypti due to the recent invasion of its ecological competitor, Ae. albopictus, has the potential to alter the landscape of arborviral disease.
Comparison of solitary and collective foraging strategies ofCaenorhabditis elegansin patchy food distributions
Authors: Ding Siyu Serena , Muhle Leah S. , Brown André E. X. , Schumacher Linus J. , Endres Robert G.
Published: August 2019

Collective foraging has been shown to benefit organisms in environments where food is patchily distributed, but whether this is true in the case where organisms do not rely on long-range communications to coordinate their collective behaviour has been understudied. To address this question, we use the tractable laboratory model organismCaenorhabditis elegans, where a social strain (npr-1mutant) and a solitary strain (N2) are available for direct comparison of foraging strategies. We first developed an on-lattice minimal model for comparing collective and solitary foraging strategies, finding that social agents benefit from feeding faster and more efficiently simply due to group formation. Our laboratory foraging experiments withnpr-1and N2 worm populations, however, show an advantage for solitary N2 in all food distribution environments that we tested. We incorporated additional strain-specific behavioural parameters ofnpr-1and N2 worms into our model and computationally identified N2’s higher feeding rate to be the key factor underlying its advantage, without which it is possible to recapitulate the advantage of collective foraging in patchy environments. Our work highlights the theoretical advantage of collective foraging due to group formation alone without long-range interactions, and the valuable role of modelling to guide experiments.
Pharmacological inhibition of the heart of glass (HEG1)-Krev interaction trapped protein 1 (KRIT1) protein complex increases Krüppel-like Factors 4 and 2 (KLF4/2) expression in endothelial cells
Authors: Lopez-Ramirez Miguel Alejandro , Haynes Mark K. , Hale Preston , Oukoloff Killian , Bautista Matthew , Gongol Brendan , Shyy John Y. , Ballatore Carlo , Sklar Larry A. , Gingras Alexandre R.
Published: August 2019

The Krüppel-like Factors 4 and 2 (KLF4/2) are transcription factors and master regulators of endothelial cells (ECs) phenotype and homeostasis. KLF4/2 are important blood-flow-responsive genes within ECs that differentially regulate the expression of factors that confer anti-inflammatory, antithrombotic, and antiproliferative effects in ECs. Genetic inactivation of endothelial KRIT1 (Krev interaction trapped protein 1) or HEG1 (Heart of glass) lead to upregulation of KLF4/2 expression levels. Furthermore, increased expression of thrombomodulin (THBD) and suppression of thrombospondin (THBS1) was ascribed to elevation of KLF4/2 as a result of loss of endothelial KRIT1. Here, we developed a high-throughput screening assay to identify inhibitors of the HEG1-KRIT1 interaction and identified, HEG1-KRIT1 inhibitor 1 (HKi1), as a promising hit inhibitor. The crystal structure of HKi1 bound to the KRIT1 FERM domain confirmed the primary screening results and ultimately led to the identification of a fragment-like inhibitor (HKi3), which occupies the HEG1 pocket producing comparable activity. These findings suggest that these inhibitors block the interaction by competing with the HEG1 for binding to KRIT1 FERM domain. Moreover, our results demonstrate that HKi3 upregulates KLF4/2 gene expression in two types of human ECs. These results reveal that acute pharmacological inhibition of the HEG1-KRIT1 interaction rapidly induces expression of KLF4/2 and their important transcriptional targets thrombomodulin and thrombospondin.
Transcription-induced formation of extrachromosomal DNA during yeast ageing
Authors: Hull Ryan , King Michelle , Pizza Grazia , Krueger Felix , Vergara Xabier , Houseley Jonathan
Published: August 2019

Extrachromosomal circular DNA (eccDNA) facilitates adaptive evolution by allowing rapid and extensive gene copy number variation, and is implicated in the pathology of cancer and ageing. Here, we demonstrate that yeast aged under environmental copper accumulate high levels of eccDNA containing the copper resistance gene CUP1. Transcription of CUP1 causes CUP1 eccDNA accumulation, which occurs in the absence of phenotypic selection. We have developed a sensitive and quantitative eccDNA sequencing pipeline that reveals CUP1 eccDNA accumulation on copper exposure to be exquisitely site specific, with no other detectable changes across the eccDNA complement. eccDNA forms de novo from the CUP1 locus through processing of DNA double-strand breaks (DSBs) by Sae2 / Mre11 and Mus81, and genome-wide analyses show that other protein coding eccDNA species in aged yeast share a similar biogenesis pathway. Although abundant we find that CUP1 eccDNA does not replicate efficiently, and high copy numbers in aged cells arise through frequent formation events combined with asymmetric DNA segregation. The transcriptional stimulation of CUP1 eccDNA formation shows that age-linked genetic change varies with transcription pattern, resulting in gene copy number profiles tailored by environment.
Open source computational simulation for a moth-inspired navigation algorithm
Authors: Benelli Noam , Gurka Roi , Golov Yiftach , Harari Ally , Zilman Gregory , Liberzon Alex
Published: August 2019

Olfactory navigation in insects, for instance when males search for mates, is a navigational problem of a self-propelled agent with limited sensor capabilities in a scalar field (odor) convected and diffused by turbulent wind. There are numerous navigation strategies proposed to explain the navigation paths of insects to food (flowers) or mating partners (females). In a search for a mate, the males use airborne pheromone puffs in turbulent environments around trees and vegetation. It is difficult to compare the various strategies because of a lack of a single simulation framework that can change a single parameter in time and test all the strategies against a controlled environment. This work aims at closing this gap, suggesting an open source, freely accessible simulation framework, abbreviated MothPy. We implement the simulation framework using another open source package (“pompy”) that recreates a state-of-the-art puff-based odor plume model of Farrell et al. [1]. We add four different navigation strategies to the simulation framework based on and extending the previously published models [2, 3], and compare their performance with different wind and odor spread parameters. We test a sensitivity analysis of the navigation strategies to the plume meandering and to increased turbulence levels that are effectively expressed as the elevated puff spread rates. The simulations are compared statistically and provide an interesting view on the robustness and effectiveness of various strategies. This benchmarking-ready simulation framework could be useful for the biology-oriented, as well as engineering-oriented studies, assisting to deduce the evolutionary efficient strategies and improving self-propelled autonomous systems in complex environments.
Evaluation of eight protocols for genomic DNA extraction of Hypostomus commersoni Valenciennes, 1836 (Loricariidae: Siluriformes)
Authors: Mezzomo P. , Mielniczki-Pereira A. A. , Sausen T. L. , Marinho J. R. , Cansian R. L.
Published: August 2019

The principle and the techniques applied in DNA extraction play a pivotal role in the obtention of a purified genetic material. The present study investigates the efficiency of eight protocols in the DNA extraction of Hypostomus commersoni, an essential component of South American freshwater ichthyofauna. The quality of samples was assessed through spectrophotometry, gel electrophoresis, and PCR-RAPD amplification. The efficiency of DNA extraction was influenced both by the method applied and the target-tissue of choice. Higher concentrations and yield of DNA were obtained from ocular tissue, with a positive spectrum of incubation in lysis buffer for up to 36 hours after sample collection, using fresh tissues and in the presence of a high concentration of Proteinase K (20 mg.ml-1). In these conditions, samples were successfully amplified. To date, there is no record of description for the parameters analyzed in this work, neither the description of RAPD markers for the species H. commersoni.
Ligand-induced Conformational Selection Predicts the Selectivity of Cysteine Protease Inhibitors
Authors: Sartori Geraldo Rodrigues , Leitão Andrei , Montanari Carlos A. , Laughton Charles A.
Published: August 2019

Cruzain, a cysteine protease of Trypanosoma cruzi, is a validated target for the treatment of Chagas disease. Due to its high similarity in three-dimensional structure with human cathepsins and their sequence identity above 70% in the active site regions, identifying potent but selective cruzain inhibitors with low side effects on the host organism represents a significant challenge. Here a panel of nitrile ligands with varying potencies against cathepsin K, cathepsin L and cruzain, are studied by molecular dynamics simulations as both non-covalent and covalent complexes. Principal component analysis (PCA), identifies and quantifies patterns of ligand-induced conformational selection that enable the construction of a decision tree which can predict with high confidence a low-nanomolar inhibitor of each of three proteins, and determine the selectivity for one against others.
ADC mapping with 12 b values: an improved technique for image quality in diffusion prostate MRI
Authors: Saad Lucas Scatigno , de Queiroz Rosas George , de Farias e Melo Homero José , Gabriele Henrique Armando Azevedo , Szejnfeld Jacob
Published: August 2019

Purpose

To compare diffusion images and coefficients obtained with 4 b-value versus 12 b-value apparent diffusion coefficient (ADC) mapping for characterization of prostate lesions and how these coefficients relate and compare to the PI-RADS™ classification and Gleason grading system.

Methods

Patients with indications for prostate cancer testing (n=158) underwent multiparametric 3T magnetic resonance imaging (MRI). Two diffusion sequences were acquired, one with 4 b values and one with 12 b values. ADC maps were calculated for each (ADC4 and ADC12) and the respective coefficients were tested for correlation with PI-RADS™ classification and Gleason score.

Results

The ADC12 sequence produced images of superior quality and sharpness than ADC4. Normal-area means (ADC4, 1793.3×10−6mm2/s; ADC12, 1100×10−6mm2/s) were significantly lower than those of lesion areas (ADC4, 1105.9×10−6mm2/s; ADC12, 689.4×10−6mm2/s) (p<0.001). Both techniques behaved similarly and correlated well with PI-RADS™ classification, distinguishing scores 3, 4, and 5 and with means tending to decline with increasing Gleason grade. ADC12 mapping yielded higher specificity than ADC4 (82.6% vs. 72.3%).

Conclusions

Diffusion with 12 values is a viable technique for examination of the prostate. It produced higher-quality images than current techniques and correlates well with PI-RADS™ classification and Gleason score.
The effect of blue-blocking lenses on photostress recovery times for low and high contrast chromatic and achromatic stimuli
Authors: Alzahrani Hind Saeed , Khuu Sieu K. , Ali Adiba , Roy Maitreyee
Published: August 2019

The selective reduction in visible wavelengths transmitted through commercially available blue-blocking lenses (BBLs) is known to influence the appearance and contrast detection of objects, particularly at low light levels which may impact the human retinal receptor response time to dynamic light changes during phostress events. In the present study, we assessed whether BBLs selectively affect photostress recovery times (PSRTs) in 12 participants for chromatic and achromatic stimuli presented under low and high contrast luminance conditions. Four types of commercially available BBLs were evaluated, and their effects on PSRTs were investigated. Our results showed that PSRTs required to detect high contrast chromatic and achromatic stimuli were unaffected by BBLs when compared to a clear control lens. However, PSRTs were significantly affected by BBLs and were longer when chromatic and achromatic stimuli were of low contrast. In addition, BBLs had the greatest impact on the PSRTs of blue coloured targets, and this was dependent on the spectral transmittance profile. These results indicate that wearing BBLs under low contrast conditions can have serious implications for visual behavior, particularly under low-light levels and in situations in which the observer is directly exposed to bright light sources. For example, during night time driving, the driver might be briefly exposed to bright lights by glancing at the headlights of a passing car. This increases the time required for vision to be restored after bright light exposure, resulting in delayed object detection, and therefore stoppage and reaction times, which might pose a safety risk for a driver.
Software for agriculture climate risk management focused in smallholders
Authors: Coltri Priscila Pereira , Pinto Hilton Silveira , de Medeiros Yasmin Onorio , Hashimoto Kaio Shinji , Di Blasio Giovanni Chaves , Alfonsi Eduardo Lauriano , do Valle Gonçalves Renata Ribeiro , Alfonsi Waldenilza Monteiro
Published: August 2019

Taking Persimmon (Diospyros kakiL.), Fig (Ficus caricaL.) and Papaya (Carica PapayaL) fruits in São Paulo State, southeast of Brazil, as a case of study, we present here new software that was designed to support smallholders to manage their climate risk on the production area. The main idea of this new software named “Brazilian Mapping for Agricultural Zoning System” (BRAMAZOS) is to transform scientific knowledge into useful information for crop climate risk management, indicating the risk of crop failure and which is the limiting meteorological element for the area unsuitability. The software was developed based on user experience design, focusing on the users facilities with a friendly interface. We simulated these fruits climate risk in current and future scenarios of climate change using ETAHadgem ES Regional Climate Models (RCM), which is a downscaling of the Global Climate Model HadGEM2-ES, based on the IPCC 5th Assessment Report (AR5). We observed changes in the climate risk zone distribution for Persimmon and Papaya cultivation, which could lose almost 30% and 9% of the suitable area respectively. On the other hand, fig did not present significant reduction in the climate risk zone. The results presented here suggested that the temperate fruit examples used here seem to be more sensible to the temperature increase and, the tropical example seems to be more precipitation decrease sensitive. We discussed the significance of BRAMAZOS software as tool to support efficient information to climate risk management, providing agroclimatic information that are efficient to assist decision making, increase food security with the intention to reduce the climate impact on smallholders development and resources management issues.
In vivo sequestration of innate small molecules to promote bone healing
Authors: Zeng Yuze , Shih Yu-Ru V. , Baht Gurpreet S. , Varghese Shyni
Published: August 2019

Approaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, we describe biomaterial-assisted sequestration of small molecules to localize pro-regenerative signaling at the injury site. Specifically, we designed a synthetic biomaterial containing boronate molecules to sequester adenosine, a small molecule ubiquitously present in the human body. The biomaterial-assisted sequestration of adenosine leverages the transient surge of extracellular adenosine following injury to prolong local adenosine signaling. We demonstrated that implantation of the biomaterial patch following injury establishes an in-situ stockpile of adenosine, resulting in accelerated healing by promoting both osteoblastogenesis and angiogenesis. The adenosine content within the patch recedes to the physiological level as the tissue regenerates. In addition to sequestering endogenous adenosine, the biomaterial is also able to deliver exogenous adenosine to the site of injury, offering a versatile solution to utilizing adenosine as a potential therapeutic for tissue repair.