bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological and clinical characteristics of the early phase of the COVID-19 epidemic in Brazil
Authors: de Souza William Marciel , Buss Lewis Fletcher , Candido Darlan da Silva , Carrera Jean-Paul , Li Sabrina , Zarebski Alexander E. , Vincenti-Gonzalez Maria F. , Messina Janey , Silva Sales Flavia Cristina da , Santos Andrade Pamela dos , Prete Carlos A. , Nascimento Vítor Heloiz , Ghilardi Fabio , Moraes Pereira Rafael Henrique , Souza Santos Andreza Aruska de , Abade Leandro , Gutierrez Bernardo , Kraemer Moritz U. G. , Aguiar Renato Santana , Alexander Neal , Mayaud Philippe , Brady Oliver J. , de Souza Izabel Oliva Marcilio , Gouveia Nelson , Li Guangdi , Tami Adriana , de Oliveira Silvano Barbosa , Gomes Porto Victor Bertollo , Ganem Fabiana , de Almeida Walquiria Aparecida Ferreira , Tardetti Fantinato Francieli Fontana Sutile , Macário Eduardo Marques , de Oliveira Wanderson Kleber , Pybus Oliver G. , Wu Chieh-Hsi , Croda Julio , Sabino Ester C. , Faria Nuno Rodrigues
Published: April 2020

Background

The first case of COVID-19 was detected in Brazil on February 25, 2020. We report the epidemiological, demographic, and clinical findings for confirmed COVID-19 cases during the first month of the epidemic in Brazil.

Methods

Individual-level and aggregated COVID-19 data were analysed to investigate demographic profiles, socioeconomic drivers and age-sex structure of COVID-19 tested cases. Basic reproduction numbers (R0) were investigated for São Paulo and Rio de Janeiro. Multivariate logistic regression analyses were used to identify symptoms associated with confirmed cases and risk factors associated with hospitalization. Laboratory diagnosis for eight respiratory viruses were obtained for 2,429 cases.

Findings

By March 25, 1,468 confirmed cases were notified in Brazil, of whom 10% (147 of 1,468) were hospitalised. Of the cases acquired locally (77·8%), two thirds (66·9% of 5,746) were confirmed in private laboratories. Overall, positive association between higher per capita income and COVID-19 diagnosis was identified. The median age of detected cases was 39 years (IQR 30-53). The median R0 was 2·9 for São Paulo and Rio de Janeiro. Cardiovascular disease/hypertension were associated with hospitalization. Co-circulation of six respiratory viruses, including influenza A and B and human rhinovirus was detected in low levels.

Interpretation

Socioeconomic disparity determines access to SARS-CoV-2 testing in Brazil. The lower median age of infection and hospitalization compared to other countries is expected due to a younger population structure. Enhanced surveillance of respiratory pathogens across socioeconomic statuses is essential to better understand and halt SARS-CoV-2 transmission.

Funding

São Paulo Research Foundation, Medical Research Council, Wellcome Trust and Royal Society.
A Simple Covid-19 Epidemic Model and Containment Policy in France
Authors: Quadrat J.-P.
Published: April 2020

We show that the standard SIR model is not effective to predict the 2019-20 coronavirus pandemic propagation. We propose a new model where the logarithm of the detected population number follows a linear dynamical system. We estimate the parameters of this system and compare models obtained with data observed from different countries. Based on the given estimator and results obtained with the Pr. Raoult’s treatment, we affirm with a reasonable degree of confidence that his “test-treat-noconfine” policy was less expensive in human lives than the”confine and wait for a proved treatment” policy adopted by the French government.
Protein synthesis is suppressed in sporadic and familial Parkinson’s Disease by LRRK2
Authors: Deshpande Prasannakumar , Flinkman Dani , Hong Ye , Goltseva Elena , Siino Valentina , Sun Lihua , Peltonen Sirkku , Elo Laura , Kaasinen Valtteri , James Peter , Coffey Eleanor T.
Published: April 2020

Gain of function LRRK2-G2019S is the most common mutation associated with both familial and sporadic Parkinson’s disease. It is expected therefore that understanding the cellular function of LRRK2 will provide much needed insight on the pathological mechanism of sporadic Parkinson’s, which is the most common form. Here we show that constitutive LRRK2 activity represses nascent protein synthesis in rodent neurons. Specifically, enzymatic inhibition of LRRK2, gene silencing or gene knockout of Lrrk2 increase translation. In the rotenone model of Parkinson’s, LRRK2 activity increases, leading to repression of translation and dopaminergic neuron atrophy both of which are prevented by LRRK2 inhibition. This is accompanied by altered phosphorylation of eIF2α-S52(↑), eIF2s2-S2(↓) and eEF2-T57(↑) in striatum/substantia nigra in a direction that signifies inhibition of protein synthesis. Significantly, LRRK2 is activated and translation is 40% reduced in Parkinson’s patient fibroblasts (G2019S and sporadic) and LRRK2 inhibition restores normal translation. In contrast, translation is unchanged in cells from multiple system atrophy patients, implying disease specificity. These findings suggest that LRRK2-dependent repression of translation may be a proximal function of LRRK2 in Parkinson’s pathology.
Detection of Merkel cell polyomavirus using whole exome sequencing data
Authors: Garcia-Mulero Sandra , Moratalla-Navarro Ferran , Curiel-Olmo Soraya , Moreno Victor , Vaqué José Pedro , Sanz-Pamplona Rebeca , María Piulats Josep
Published: April 2020

Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin in which Merkel cell polyomavirus (MCV) DNA virus insertion can be detected in 75–89% of cases. Etiologic and phenotypic differences exist between MCC tumors with and without the inserted virus, thus it is important to distinguish between MCV+ MCC and MCV-MCC cases. Currently, MCV insertions in MCC genomes are detected using laboratory techniques. Here we report a freely available bioinformatics methodology to identify MCV+ MCC tumors using whole exome sequencing (WES) data. WES data could be also used to infer the virus insertion site into the tumor genome. Our method has been validated in a set of MCC samples previously characterized in the laboratory as MCV+ or MCV-, achieving 100% sensitivity and 62,5% specificity. Thus, with enough depth of sequencing, it is possible to use WES to the presence of MCV insertions in cancer samples.
Volumetric two-photon fluorescence imaging of live neurons using a multimode optical fiber
Authors: Turcotte Raphaël , Schmidt Carla C. , Booth Martin J. , Emptage Nigel J.
Published: April 2020

Multimode optical fibers (MMFs), combined with wavefront control methods, have achieved minimally-invasivein vivoimaging of neurons in deep-brain regions with diffraction-limited spatial resolution. Here, we report a method for volumetric two-photon fluorescence imaging with a MMF-based system requiring a single transmission matrix measurement. Central to this method is the use of a laser source able to generate both continuous wave light and femtosecond pulses. The chromatic spreading of pulses generated an axially elongated excitation focus, which we used to demonstrate volumetric imaging of neurons and their dendrites in live rat brain slices through a 60 μm-core MMF.
Developmentally regulated PERK activity renders dendritic cells insensitive to subtilase cytotoxin-induced integrated stress response
Authors: Mendes Andreia , Gigan Julien P. , Rodrigues Christian Rodriguez , Choteau Sébastien A. , Sanseau Doriane , Barros Daniela , Almeida Catarina , Camosseto Voahirana , Argüello Rafael J. , Chasson Lionel , Paton Adrienne W. , Paton James C. , Lennon-Duménil Ana-Maria , Gatti Evelina , Pierre Philippe
Published: April 2020

In stressed cells, phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation and gene expression known as the integrated stress response (ISR). We show here that dendritic cells (DCs) display unusually high eIF2α phosphorylation, which is mostly caused by a developmentally regulated activation of the ER kinase PERK (EIF2AK3). Despite high p-eIF2α levels, differentiated DCs display active protein synthesis and no signs of a chronic ISR. eIF2α phosphorylation does not majorly impact DC differentiation nor cytokines production. It is however important to adapt protein homeostasis to the variations imposed on DCs by the immune or physiological contexts. This biochemical specificity prevents translation arrest and expression of the transcription factor ATF4 during ER-stress induction by subtilase cytotoxin or upon DC stimulation with bacterial lipopolysaccharides. This is also exemplified by the influence of the actin cytoskeleton dynamics on eIF2α phosphorylation and the migratory deficit observed in PERK-deficient DCs.
Relating network analyses to phylogenetic relatedness to infer protistan co-occurrences and co-exclusions in marine and terrestrial environments
Authors: Lentendu Guillaume , Dunthorn Micah
Published: April 2020

We used two large-scale metabarcoding datasets to evaluate phylogenetic signals at global marine and regional terrestrial scales using co-occurrence and co-exclusion networks. Phylogenetic relatedness was estimated using either global pairwise sequence distance or phylogenetic distance and the significance of observed patterns relating networks and phylogenies were evaluated against two null models. In all datasets, we found that phylogenetically close OTUs significantly co-occurred more often, and OTUs with intermediate phylogenetic relatedness co-occurred less often, than expected by chance. Phylogenetically close OTUs co-excluded less often than expected by chance in the marine datasets only. Simultaneous excess of co-occurrences and co-exclusions were observed in the inversion zone between close and intermediate phylogenetic distance classes in marine surface. Similar patterns were observed by using either pairwise sequence or phylogenetic distances, and by using both null models. These results suggest that environmental filtering and dispersal limitation are the preponderant forces driving co-occurrence of protists in both environments, while signal of competitive exclusion was only detected in the marine surface environment. The discrepancy in the co-exclusion pattern is potentially linked to the individual environments: water bodies are more homogeneous while tropical forest soils contain a myriad of nutrient rich micro-environment reducing the strength of mutual exclusion.
Recalibrating the Epigenetic Clock: Implications for Assessing Biological Age in the Human Cortex
Authors: Shireby Gemma L , Davies Jonathan P , Francis Paul T , Burrage Joe , Walker Emma M , Neilson Grant W A , Dahir Aisha , Thomas Alan J , Love Seth , Smith Rebecca G , Lunnon Katie , Kumari Meena , Schalkwyk Leonard C , Morgan Kevin , Brookes Keeley , Hannon Eilis J , Mill Jonathan
Published: April 2020

Human DNA-methylation data have been used to develop biomarkers of ageing - referred to ‘epigenetic clocks’ - that have been widely used to identify differences between chronological age and biological age in health and disease including neurodegeneration, dementia and other brain phenotypes. Existing DNA methylation clocks are highly accurate in blood but are less precise when used in older samples or on brain tissue. We aimed to develop a novel epigenetic clock that performs optimally in human cortex tissue and has the potential to identify phenotypes associated with biological ageing in the brain. We generated an extensive dataset of human cortex DNA methylation data spanning the life-course (n = 1,397, ages = 1 to 104 years). This dataset was split into ‘training’ and ‘testing’ samples (training: n = 1,047; testing: n = 350). DNA methylation age estimators were derived using a transformed version of chronological age on DNA methylation at specific sites using elastic net regression, a supervised machine learning method. The cortical clock was subsequently validated in a novel human cortex dataset (n = 1,221, ages = 41 to 104 years) and tested for specificity in a large whole blood dataset (n = 1,175, ages = 28 to 98 years). We identified a set of 347 DNA methylation sites that, in combination optimally predict age in the human cortex. The sum of DNA methylation levels at these sites weighted by their regression coefficients provide the cortical DNA methylation clock age estimate. The novel clock dramatically out-performed previously reported clocks in additional cortical datasets. Our findings suggest that previous associations between predicted DNA methylation age and neurodegenerative phenotypes might represent false positives resulting from clocks not robustly calibrated to the tissue being tested and for phenotypes that become manifest in older ages. The age distribution and tissue type of samples included in training datasets need to be considered when building and applying epigenetic clock algorithms to human epidemiological or disease cohorts.
Metabolic exchange and energetic coupling between nutritionally stressed bacterial species, the possible role of QS molecules
Authors: Ranava David , Backes Cassandra , Karthikeyan Ganesan , Ouari Olivier , Soric Audrey , Guiral Marianne , Cárdenas María Luz , Giudici-Orticoni Marie Thérèse
Published: April 2020

To clarify the principles controlling inter-species interactions, we previously developed a co-culture model with two anaerobic bacteria, Clostridium acetobutylicum and Desulfovibrio vulgaris Hildenborough, in which nutritional stress for D. vulgaris induced tight cell-cell inter-species interaction. Here we show that exchange of metabolites produced by C. acetobutylicum allows D. vulgaris to duplicate its DNA, and to be energetically viable even without its substrates. Physical interaction between C. acetobutylicum and D. vulgaris (or Escherichia coli and D. vulgaris) is linked to the quorum-sensing molecule AI-2, produced by C. acetobutylicum and E. coli. With nutrients D. vulgaris produces a small molecule that inhibits in vitro the AI-2 activity, and could act as an antagonist in vivo. Sensing of AI-2 by D. vulgaris could induce formation of an intercellular structure that allows directly or indirectly metabolic exchange and energetic coupling between the two bacteria.
Alternative phage-host interaction inLactococcus lactis: the carrier state drives rapid evolution of phages
Authors: Marcelli Barbara , de Jong Anne , Janzen Thomas , Kok Jan , Kuipers Oscar P.
Published: April 2020

Lactococcus lactisis a lactic acid bacterium widely used as starter culture for the manufacture of fermented milk products like quark, buttermilk and cheese. Bacteriophage infection of starter cultures is one of the biggest causes of fermentation failure and, therefore, lactococcal phages have received great attention from the scientific community in the past decades. In this work we present evidence for the establishment of a carrier state life cycle (CSLC) by a bacteriophage belonging to the c2 species, in the model laboratory strainL. lactisMG1363. Our results show that infection ofL. lactisMG1363 with a second, dissimilar, c2 bacteriophage can induce the CSLC phage to enter an active lytic life cycle. The viral progeny obtained after this infection is a mixed population of phages with differences in their genome sequences and host ranges, indicative of an extremely rapid evolution process. We discuss the possible implications of this phage-host interaction, both with respect to bacteriophage evolution and phage adaptation to different hosts.

IMPORTANCE

Our results broaden the current know-how on the yet poorly investigated phage-host interaction mechanism of CSLC, propose a new bacteriophage evolution mechanism, and demonstrate that the outcome of phage infections is possibly more intricate than presently acknowledged.
MOSAIC: A Joint Modeling Methodology for Combined Circadian and Non-Circadian Analysis of Multi-Omics Data
Authors: De los Santos Hannah , Bennett Kristin P. , Hurley Jennifer M.
Published: April 2020

Motivation

Circadian rhythms are approximately 24 hour endogenous cycles that control many biological functions. To identify these rhythms, biological samples are taken over circadian time and analyzed using a single omics type, such as transcriptomics or proteomics. By comparing data from these single omics approaches, it has been shown that transcriptional rhythms are not necessarily conserved at the protein level, implying extensive circadian post-transcriptional regulation. However, as proteomics methods are known to be noisier than transcriptomic methods, this suggests that previously identified arrhythmic proteins with rhythmic transcripts could have been missed due to noise and may not be due to post-transcriptional regulation.

Results

To determine if one can use information from less-noisy transcriptomic data to inform rhythms in more-noisy proteomic data, and thus more accurately identify rhythms in the proteome, we have created the MOSAIC (Multi-Omics Selection with Amplitude Independent Criteria) application. MOSAIC combines model selection and joint modeling of multiple omics types to recover significant circadian and non-circadian trends. Using both synthetic data and proteomic data fromNeurospora crassa, we showed that MOSAIC accurately recovers circadian rhythms at higher rates in not only the proteome but the transcriptome as well, outperforming existing methods for rhythm identification. In addition, by quantifying non-circadian trends in addition to circadian trends in data, our methodology allowed for the recognition of the diversity of circadian regulation as compared to non-circadian regulation.

Availability

MOSAIC’s full interface is available athttps://github.com/delosh653/MOSAIC.

Contact

hurlej2@rpi.edu

Supplementary information

Supplementary data are available.atBioinformaticsonline.
Transcriptome Sequencing Reveals Sex Differences in Human Meniscal Cell Response to Estrogen Based on Dosing Kinetics
Authors: Knewtson Kelsey E. , Gonzalez Flores Jesus G. , Pacicca Donna M. , Robinson Jennifer L.
Published: April 2020

Osteoarthritis is a disease marked by progressive and irreversible hyaline cartilage and fibrocartilage breakdown that affects the lives of millions of patients worldwide. Female sex and menopause are both risk factors for knee osteoarthritis, indicating that estrogen could play a role in this disease. In this study, RNA sequencing was used to determine the effects of estrogen treatment on human meniscal cells. Differences in the number and type of differentially expressed genes were seen based on donor sex, estrogen dose, and dosing kinetics. Significantly more differentially expressed genes were seen from male meniscal cells in response to all dosing conditions compared to female cells. Importantly, more genes were differentially expressed in cells treated with continuous dosing of estrogen, which has been shown to stimulate genomic estrogen signaling, as compared to pulsed dosing. Additionally, functional enrichment analysis revealed that many genes of the extracellular matrix, which is important for joint health and injury repair, were differentially expressed. Overall, this initial study lays the groundwork for future avenues to pursue the effect of estrogen delivery on regenerative pathways. This critical analysis will then inform the design and implementation of estrogen replacement therapies to promote meniscal health and reduce the onset of osteoarthritis.
A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior
Authors: Ramachandran Shankar , Banerjee Navonil , Bhattacharya Raja , Lemons Michele L , Florman Jeremy , Lambert Christopher M. , Touroutine Denis , Alexander Kellianne , Schoofs Liliane , Alkema Mark J , Beets Isabel , Francis Michael M.
Published: April 2020

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here we show that theC. elegansNLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We showckr-2deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion ofckr-1reduces head neuron activity and diminishes turning while specificckr-1overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits.

Impact statement

Investigation of neuromodulatory control of ethologically conserved area-restricted food search behavior shows that NLP-12 stimulation of the head motor circuit promotes food searching through the previously uncharacterized CKR-1 GPCR.
Universal NicE-seq for high resolution accessible chromatin profiling for formaldehyde fixed and FFPE tissues
Authors: Chin Hang Gyeong , Sun Zhiyi , Vishnu Udayakumar S. , Hao Christina , Cejas Paloma , Spracklin George , Estève Pierre-Olivier , Xu Shuang-yong , Long Henry W. , Pradhan Sriharsa
Published: April 2020

Accessible chromatin plays a central role in gene expression and chromatin architecture. Current accessible chromatin approaches depend on limited digestion/cutting and pasting adaptors at the accessible DNA, thus requiring additional materials and time for optimization. Universal NicE-seq (UniNicE-seq) is an improved accessible chromatin profiling method that negate the optimization step and is suited to a variety of mammalian cells and tissues. Addition of 5-methyldeoxycytidine triphosphate during accessible chromatin labeling and an on-bead library making step substantially improved the signal to noise ratio while protecting the accessible regions from repeated nicking in cell lines, mouse T cells, mouse kidney, and human frozen tissue sections. We also demonstrate one tube UniNicE-seq for FFPE tissue section for direct NGS library preparation without sonication and DNA purification steps. These refinements allowed reliable mapping of accessible chromatin for high resolution genomic feature studies.
Age-Related Changes in Chimpanzee (Pan troglodytes) Cognition: Cross-Sectional and Longitudinal Analyses
Authors: Hopkins William D , Mareno Mary Catherine , Webb Sarah J Neal , Schapiro Steve J , Raghanti Mary Ann , Sherwood Chet C
Published: April 2020

Chimpanzees are the species most closely related to humans yet age-related changes in brain and cognition remain poorly understood. The lack of studies on age-related changes in cognition in chimpanzees is particularly unfortunate in light of the recent evidence demonstrating that this species naturally develops Alzheimer’s disease (AD) neuropathology. Here, we tested 213 young, middle-aged, and elderly chimpanzees on the Primate Cognitive Test Battery (PCTB), a set of 13 tasks that assess physical and social cognition in nonhuman primates. A subset of these chimpanzees (n=146) were tested a second time on a portion of the PCTB tasks as a means of evaluating longitudinal changes in cognition. Cross-sectional analyses revealed a significant quadratic association between age and cognition with younger and older chimpanzees performing more poorly than middle-aged individuals. Longitudinal analyses showed that, while young chimpanzees’ performance improved from test 1 to test 2, middle-aged and elderly chimpanzees’ performance showed significant decline over time. The collective data show that chimpanzees, like other nonhuman primates, show age-related decline in cognition. Further investigations into whether the observed cognitive decline is associated with AD pathologies in chimpanzees would be invaluable in understanding the comparative biology of aging and neuropathology in primates.
Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure
Authors: Rasiah Neilen , Rosenegger David , Daviu Nuria , Füzesi Tamás , Muir Jessie , Sterley Toni-Lee , Bains Jaideep S.
Published: April 2020

An increase in circulating glucocorticoids (CORT) is an essential part of the response to stress. Sustained elevations of CORT, however, have dramatic consequences on behavior, endocrine systems and peripheral organs. Critically, they dampen the endocrine response to acute challenges and decrease intrinsic excitability of corticotropin-releasing hormone neurons in the paraventricular nucleus (CRHPVN), suggesting key circuits may be less responsive to stress. Here, we make the surprising discovery that CRHPVNneurons harness a form of adaptive synaptic scaling to escape the persistent negative feedback pressure from CORT and maintain stable outputin vivo. Specifically, there is an increase in glutamatergic drive to these cells that is mediated by a postsynaptic, multiplicative increase in synaptic strength. These findings suggest that dysfunctions associated with chronic stress may not be due to the primary actions of CORT, but instead reflect the emergence of synaptic adaptations as networks seek to re-establish intrinsic activity setpoints.
Nano-positioning and tubuline conformation determine transport of mitochondria along microtubules
Authors: Van Steenbergen V. , Lavoie-Cardinal F. , Kazwiny Y. , Decet M. , Martens T. , Verstreken P. , Boesmans W. , De Koninck P. , Berghe P. Vanden
Published: April 2020

Correct spatiotemporal distribution of organelles and vesicles is crucial for healthy cell functioning and is regulated by intracellular transport mechanisms. Controlled transport of bulky mitochondria is especially important in polarized cells such as neurons that rely on these organelles to locally produce energy and buffer calcium. Mitochondrial transport requires and depends on microtubules which fill much of the available axonal space. How mitochondrial transport is affected by their position within the microtubule bundles is not known. Here, we found that anterograde transport, driven by kinesin motors, is susceptible to the molecular conformation of tubulin bothin vitroandin vivo. Anterograde velocities negatively correlate with the density of elongated tubulin dimers, similar to GTP-tubulin, that are more straight and rigid. The impact of the tubulin conformation depends primarily on where a mitochondrion is positioned, either within or at the rim of microtubule bundle. Increasing elongated tubulin levels lowers the number of motile anterograde mitochondria within the microtubule bundle and increases anterograde transport speed at the microtubule bundle rim. We demonstrate that the increased kinesin step processivity on microtubules consisting of elongated dimers underlies increased mitochondrial dynamics. Our work indicates that the molecular conformation of tubulin controls mitochondrial motility and as such locally regulates the distribution of mitochondria along axons.
Engineering Highly Homogenous Tetravalent IgGs with Enhanced Sperm Agglutination Potency
Authors: Shrestha Bhawana , Schaefer Alison , Chavez Elizabeth C. , Kopp Alexander J. , Jacobs Timothy M. , Moench Thomas R. , Lai Samuel K.
Published: April 2020

Millions of women avoid using available contraceptives and risk unintended pregnancies every year, due to perceived and/or real side-effects associated with the use of exogenous hormones. Naturally occurring anti-sperm antibodies can prevent fertilization in immune infertile women by limiting sperm permeation through mucus, particularly multivalent antibodies such as sIgA that offers robust agglutination potencies. Unfortunately, sIgA remains challenging to produce in large quantities and easily aggregates. Here, we designed two tetravalent anti-sperm IgGs with a Fab domain previously isolated from an immune infertile woman. Both constructs possess at least 4-fold greater agglutination potency and induced much more rapid sperm agglutination than the parent IgG while exhibiting comparable production yields and identical thermostability as the parent IgG. These tetravalent IgGs offer promise for non-hormonal contraception and underscore the multimerization of IgG as a promising strategy to improve existing mAb therapeutics.
In silicoCharacterization of Class II Plant Defensins fromArabidopsis thaliana
Authors: Costa Laura S.M. , Pires Állan S. , Damaceno Neila B. , Rigueiras Pietra O. , Maximiano Mariana R. , Franco Octavio L. , Porto William F.
Published: April 2020

Defensins comprise a polyphyletic group of multifunctional defense peptides. Cis-defensins, also known as cysteine stabilized αβ (CSαβ) defensins, are one of the most ancient defense peptide families. In plants, these peptides have been divided into two classes, according to their precursor organization. Class I defensins are composed of the signal peptide and the mature sequence, while class II defensins have an additional C-terminal prodomain, which is proteolytically cleaved. Class II defensins have been described in Solanaceae and Poaceae species, indicating this class could be spread among all flowering plants. Here, a search by regular expression (RegEx) was applied to theArabidopsis thalianaproteome, a model plant with more than 300 predicted defensin genes. Two sequences were identified, A7REG2 and A7REG4, which have a typical plant defensin structure and an additional C-terminal prodomain. TraVA database indicated they are expressed in flower, ovules and seeds, and being duplicated genes, this indicates they could be a result of a subfunctionalization process. The presence of class II defensin sequences in Brassicaceae and Solanaceae and evolutionary distance between them suggest class II defensins may be present in other eudicots. Discovery of class II defensins in other plants could shed some light on flower, ovules and seed physiology, as this class is expressed in these locations.
Prevalence of asymptomatic glioma and implications for survival
Authors: Warren Paula Province , Lobbous Mina , Peeri Noah C. , Thompson Zachary J. , Thompson Reid C. , Olson Jeffrey J. , LaRocca Renato V. , Chowdhary Sajeel A. , Anderson Mark D. , Vogelbaum Michael A. , Markert James M. , Nabors Louis B. , Egan Kathleen M.
Published: April 2020

Background

Brain tumors can present as focal neurologic deficits (reflecting the tumor location) or generalized symptoms due to increased intracranial pressure. Occasionally, brain tumors can be found incidentally in asymptomatic patients or in patients with unrelated symptoms who undergo brain imaging. The term incidentaloma is used to refer to these imaging abnormalities.

Objective

The object of this study was to examine the prevalence and correlates of asymptomatic glioma in a large epidemiological study of brain tumors.

Methods

The analysis was based on a large series of patients with glioma (N = 1989) enrolled in a multicenter clinic-based epidemiologic study between 2005 and 2017. Patients were considered asymptomatic from the tumor, and thus as having an incidentally detected glioma (IDG), if the tumor was diagnosed during workup of injury or unrelated medical condition.

Results

A total of 32 of 1989 (1.6%) patients were asymptomatic at diagnosis. The leading indication for brain imaging in IDG was non-workplace injuries followed by medical workup for unrelated conditions. IDG was more prevalent in patients younger than 50 years of age (2.6% vs 1.0%). IDG was also more common in patients with low grade gliomas (4.7% for WHO grade II and 1.5% for WHO grade III) vs glioblastomas (0.6% in WHO grade IV).

Conclusion

The present data suggest that gliomas may be found incidentally, especially among low grade gliomas. Studies of IDG may be useful as a proxy for early detection of tumor as a means to improve patient survival.
Functional data analysis techniques to improve the generalizability of near-infrared spectral data for monitoring mosquito populations
Authors: Esperança Pedro M. , Da Dari F. , Lambert Ben , Dabiré Roch K. , Churcher Thomas S.
Published: April 2020

Near infrared spectroscopy is increasingly being used as an economical method to monitor mosquito vector populations in support of disease control. Despite this rise in popularity, strong geographical variation in spectra has proven an issue for generalising predictions from one location to another. Here, we use a functional data analysis approach—which models spectra as smooth curves rather than as a discrete set of points—to develop a method that is robust to geographic heterogeneity. Specifically, we use a penalised generalised linear modelling framework which includes efficient functional representation of spectra, spectral smoothing and regularisation. To ensure better generalisation of model predictions from one training set to another, we use cross-validation procedures favouring smoother representation of spectra. To illustrate the performance of our approach, we collected spectra for field-caught specimens ofAnopheles gambiaecomplex mosquitoes – the most epidemiologically important vector species on the planet – in two sites in Burkina Faso. Using these spectra, we show how models trained on data from one site can successfully classify morphologically identical sibling species in another site, over 250km away. Whilst we apply our framework to species prediction, our unified statistical framework can, alternatively, handle regression analysis (for example, to determine mosquito age) and other types of multinomial classification (for example, to determine infection status). To make our methods readily available for field entomologists, we have created an open-source R packagemlevcm. All data used is publicly also available.
A functional screen of translated pancreatic lncRNAs identifies a microprotein-independent role forLINC00261in endocrine cell differentiation
Authors: Gaertner Bjoern , van Heesch Sebastiaan , Schneider-Lunitz Valentin , Schulz Jana Felicitas , Witte Franziska , Blachut Susanne , Nguyen Steven , Wong Regina , Matta Ileana , Hubner Norbert , Sander Maike
Published: April 2020

Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Here, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated during pancreas development. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for endocrine cell differentiation. However, deletion ofLINC00261diminishes generation of insulin+endocrine cells, in a manner independent of the nearby TFFOXA2. Systematic deletion of each ofLINC00261’s seven poorly conserved microproteins shows that the RNA, rather than the microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs into recently evolved microproteins during human pancreas development and provides a blueprint for dissection of their coding and noncoding roles.

Graphical Abstract

Highlights

Extensive lncRNA translation and microprotein production during human pancreas development

A small-scale loss-of-function screen shows most translated lncRNAs are dispensable

LINC00261is highly translated and regulates endocrine cell differentiation

DeletingLINC00261’s evolutionary young microproteins reveals no essential roles
ECS-based investigation of chloroplast ATP synthase regulation
Authors: Buchert Felix , Bailleul Benjamin , Joliot Pierre
Published: April 2020

The chloroplast ATP synthase (CF1Fo) contains a specific feature to the green lineage: a γ-subunit redox domain which contains a cysteine couple and interacts with the torque-generating βDELSEED-loop. Based on the recently solved structure of this domain, it was proposed to function as a chock.In vitro,γ-disulfide formation slows down the activity of the CF1Foat low transmembrane electrochemical proton gradient. Here, we utilizein vivoabsorption spectroscopy measurements for functional CF1Foactivity characterization in Arabidopsis leaves. The spectroscopic method allows us to measure thepresent in dark-adapted leaves, and to identify its mitochondrial sources. Furthermore, we follow the fate of the extragenerated by an illumination, including its osmotic and electric components, and from there we estimate the lifetime of the light-generated ATP. In contrast with a previous report [Joliot and Joliot, Biochim. Biophys. Acta, 1777 (2008) 676-683], the CF1Foγ-subunit exists mostly in an oxidized form in the dark-adapted state. To study the redox regulation of the CF1Fo, we used thiol agent infiltration in WT and a mutant that does not form the γ-disulfide. The obtained-dependent CF1Foactivity profile in the two γ-redox statesin vivoreconciles with previous biochemicalin vitrofindings [Junesch and Gräber, Biochim. Biophys. Acta, 893 (1987) 275-288]. The highest rates of ATP synthesis we measured in the two γ-redox state were similar at high. In the presence of the γ-dithiol, similar rates were obtained at a ~45 mV lowervalue compared to the oxidized state, which closely resembled the energetic gap of 0.7 ΔpH units reportedin vitro.
Riemannian geometry and statistical modeling correct for batch effects and control false discoveries in single-cell surface protein count data from CITE-seq
Authors: Zhang Shuyi , Leistico Jacob R. , Cook Christopher , Liu Yale , Cho Raymond J. , Cheng Jeffrey B. , Song Jun S.
Published: April 2020

Recent advances in next generation sequencing-based single-cell technologies have allowed high-throughput quantitative detection of cell-surface proteins along with the transcriptome in individual cells, extending our understanding of the heterogeneity of cell populations in diverse tissues that are in different diseased states or under different experimental conditions. Count data of surface proteins from the cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) technology pose new computational challenges, and there is currently a dearth of rigorous mathematical tools for analyzing the data. This work utilizes concepts and ideas from Riemannian geometry to remove batch effects between samples and develops a statistical framework for distinguishing positive signals from background noise. The strengths of these approaches are demonstrated on two independent CITE-seq data sets in mouse and human. Python source code implementing the algorithms is available athttps://github.com/jssong-lab/SAGACITE.
Population structure and genomic evidence for local adaptation to freshwater and marine environments in anadromous Arctic Char (Salvelinus alpinus) throughout Nunavik, Québec, Canada
Authors: Dallaire Xavier , Normandeau Éric , Mainguy Julien , Tremblay Jean-Éric , Bernatchez Louis , Moore Jean-Sébastien
Published: April 2020

Distinguishing neutral and adaptive genetic variation is one of the main challenges in investigating processes shaping population structure in the wild, and landscape genomics can help identify signatures of adaptation to contrasting environments. Arctic Char (Salvelinus alpinus) is an anadromous salmonid and the most harvested fish species by Inuit people, particularly so in Nunavik (Canada), one of the most recently deglaciated region in the world. Unlike most other anadromous salmonids, Arctic Char occupy coastal habitats near their overwintering rivers during their marine phase. The main objective of this study was to document the putative neutral and adaptive genomic variation of anadromous Arctic Char populations in Nunavik (Québec, Canada) and bordering regions. A second objective was to interpret our results in the context of fisheries management in Nunavik. We used genotyping-by-sequencing (GBS) to genotype 18,112 filtered single nucleotide polymorphisms (SNPs) for 650 individuals sampled in 23 locations (average sample size per location = 28) along >2,000 km of coastline. Our results reveal a hierarchical genetic structure, whereby neighboring hydrographic systems harbour distinct populations grouping within major oceanographic basins, namely the Hudson Bay, Hudson Strait, Ungava Bay and Labrador Sea. We found genetic diversity and differentiation to be consistent with both the expected post-glacial recolonization history and patterns of isolation-by-distance reflecting contemporary gene flow. Furthermore, using three gene-environment association (GEA) methods we found genomic evidence for local adaptation to freshwater and marine environmental components, especially in relation to sea-surface and air temperatures during summer, as well as salinity. Our results support fisheries management at a regional level, and other implications on hatchery projects and adaptation to climate change are discussed.
ID30A-3 (MASSIF-3) – a beamline for macromolecular crystallography at the ESRF with a small intense beam
Authors: von Stetten David , Carpentier Philippe , Flot David , Beteva Antonia , Caserotto Hugo , Dobias Fabien , Guijarro Matias , Giraud Thierry , Lentini Mario , McSweeney Sean , Royant Antoine , Petitdemange Sebastien , Sinoir Jeremy , Surr John , Svensson Olof , Theveneau Pascal , Leonard Gordon A. , Mueller-Dieckmann Christoph
Published: April 2020

ID30A-3 (or MASSIF-3) is a mini-focus (beam size 18 µm × 14 µm) highly intense (2.0 × 1013 photons s−1), fixed-energy (12.81 keV) beamline for macromolecular crystallography (MX) experiments at the European Synchrotron Radiation Facility (ESRF). MASSIF-3 is one of two fixed-energy beamlines sited on the first branch of the canted undulator setup on the ESRF ID30 port and is equipped with a MD2 micro-diffractometer, a Flex HCD sample changer, and an Eiger X 4M fast hybrid photon-counting detector. MASSIF-3 is recommended for collecting diffraction data from single small crystals (≤15 µm in one dimension) or for experiments using serial methods. The end-station has been in full user operation since December 2014, and here its current characteristics and capabilities are described.
Using text mining to track changes in travel destination image: the case of Macau
Authors: Liu Matthew Tingchi , Liu Yongdan , Mo Ziying , Ng Kai Lam
Published: April 2020

Purpose

Travel websites allow tourists to share their thoughts, beliefs and experiences regarding various travel destinations. In this paper, the researchers demonstrated an approach for destination marketing organisations to explore online tourist-generated content and understand tourists' perceptions of the destination image (DI). Specifically, the researchers initiated an investigation examining how the destination image of Macau changed during the period of 2014–2018 based on user-generated content on travel websites.

Design/methodology/approach

Web crawlers developed by Python were employed to collect tourists' reviews from both Ctrip and TripAdvisor regarding the theme of “Macau attraction”. A total of 51,191 reviews (41,352 from Ctrip and 9,839 from TripAdvisor) were collected and analysed using the text-mining technique.

Findings

The results reveal that the frequency of casino-related words decreased in reviews by both international and mainland Chinese tourists. Additionally, international and mainland Chinese tourists perceive the DI of Macau differently. Mainland Chinese tourists are more sensitive to new attractions, while international tourists are not. The study also shows that there are differences between the government-projected DI and the tourist-perceived DI. Only the “City of Culture” and “A World Centre of Tourism and Leisure” have built recognition with tourists.

Originality/value

Given the easy accessibility of online information from various sources, it is important for destination marketing organisations to analyse and monitor different DI perspectives and adjust their branding strategies for greater effectiveness. This study uncovered the online DI of Macau by using text mining and content analysis of two of the largest travel websites. By analysing and comparing the differences and relationships among the frequently used words of tourist-generated content on these websites, the researchers revealed some interesting findings with important marketing implications.
An exploratory assessment of infrastructure resilience to disasters
Authors: Lee Dae Woong
Published: April 2020

Purpose

This study aims to provide an analysis and evaluation of infrastructure resilience, one of the components of disaster resilience, to natural hazards.

Design/methodology/approach

The analysis of this study consists of four stages. First, descriptive statistical analyses were carried out on the soft and hard infrastructure resilience and natural hazard index. Second, the spatial data were visualized through the exploratory spatial data analysis to understand the spatial distribution and spatial characteristics of variables of the data. Third, the local indicators of the spatial association method were used to identify areas in clusters where infrastructure resilience is weak. Fourth, comparisons were made between the soft and hard infrastructure resilience and natural hazard index: the level of natural hazard is high but the soft and infrastructure resilience remain very vulnerable to disaster.

Findings

The study found that infrastructure resilience varies from community to community, particularly in the same community, in terms of hard infrastructure and soft infrastructure. In addition, the comparative analysis between infrastructure resilience and disaster risk levels resulted in communities that were likely to suffer greatly in the event of a disaster.

Originality/value

This study is meaningful in that infrastructure resilience of Korean local governments was discussed by dividing them into soft and hard infrastructure and comparing them to natural disaster risk levels. In particular, the comparison with the natural disaster risk level identified local governments that are likely to experience significant damage from the natural disaster, which is meaningful in that it serves as a basis for policy practitioners to actively build infrastructure and respond to disasters.
How can gamification be incorporated into disaster emergency planning? A systematic review of the literature
Authors: Kankanamge Nayomi , Yigitcanlar Tan , Goonetilleke Ashantha , Kamruzzaman Md.
Published: April 2020

Purpose

The purpose of this paper is to investigate the role of gamification as a novel technique in motivating community engagement in disaster-related activities in order to address the question of how gamification can be incorporated into disaster emergency planning.

Design/methodology/approach

This study conducts a systematic literature review and explores available gamified applications for disaster emergency planning and their purpose of use. In total, 51 scholarly articles on the topic and 35 disaster-related gamified applications are reviewed.

Findings

The findings reveal the following: (a) gamified applications (n = 35) are used for education, research and intervention purposes; (b) gamified applications create new opportunities for community engagement and raise disaster awareness among the community in virtual environments; and (c) gamified applications help shape a new culture – i.e. gamified culture – that supports smart disaster emergency planning practice.

Originality/value

During the recent years, utilisation of game elements in non-game contexts – i.e., gamification – has become a popular approach in motivating people in various actions. Increasing research highlighted the benefits of gamification in enhancing community engagement, creating interactive environments, providing better behavioural outcomes and influencing democratic processes. Despite some of the applications indicating the potential of gamification in disaster emergency planning, the use of gamification technique in this discipline is an understudied area. This study reveals gamification can be incorporated into disaster emergency planning.