bluuebunny/crossref_metadata_2025 huggingface dataset:
Oligocene divergence of frogmouth birds (Podargidae) across Wallace's Line
Authors: Oliver Paul M. , Heiniger Holly , Hugall Andrew F. , Joseph Leo , Mitchell Kieren J.
Published: May 2020

Wallace's Line demarcates the transition between the differentiated regional faunas of Asia and Australia. However, while patterns of biotic differentiation across these two continental landmasses and the intervening island groups (Wallacea) have been extensively studied, patterns of long-term dispersal and diversification across this region are less well understood. Frogmouths (Aves: Podargidae) are a relictual family of large nocturnal birds represented by three extant genera occurring, respectively, in Asia, ‘Sahul’ (Australia and New Guinea) and the Solomon Islands, thus spanning Wallace's Line. We used new mitochondrial genomes from each of the extant frogmouth genera to estimate the timeline of frogmouth evolution and dispersal across Wallace's Line. Our results suggest that the three genera diverged and dispersed during the mid-Cenozoic between approximately 30 and 40 Mya. These divergences are among the oldest inferred for any trans-Wallacean vertebrate lineage. In addition, our results reveal that the monotypic Solomons frogmouth (
Rigidipenna inexpectata
) is one of the most phylogenetically divergent endemic bird lineages in the southwest Pacific. We suggest that the contemporary distribution of exceptionally deep divergences among extant frogmouth lineages may be explained by colonization of, and subsequent long-term persistence on, island arcs in the southwest Pacific during the Oligocene. These island arcs may have provided a pathway for biotic dispersal out of both Asia and Australia that preceded the formation of extensive emergent landmasses in Wallacea by at least 10 million years.
An irregular hourglass pattern describes the tempo of phenotypic development in placental mammal evolution
Authors: Cordero Gerardo A. , Sánchez-Villagra Marcelo R. , Werneburg Ingmar
Published: May 2020

Organismal development is defined by progressive transformations that ultimately give rise to distinct tissues and organs. Thus, temporal shifts in ontogeny often reflect key phenotypic differences in phylogeny. Classical theory predicts that interspecific morphological divergence originates towards the end of embryonic or fetal life stages, i.e. the early conservation model. By contrast, the hourglass model predicts interspecific variation early and late in prenatal ontogeny, though with a phylogenetically similar mid-developmental period. This phylotypic period, however, remains challenging to define within large clades such as mammals. Thus, molecular and morphological tests on a mammalian hourglass have not been entirely congruent. Here, we report an hourglass-like pattern for mammalian developmental evolution. By comparing published data on the timing of 74 homologous characters across 51 placental species, we demonstrated that variation in the timing of development decreased late in embryogenesis––when organ formation is highly active. Evolutionary rates of characters related to this timeframe were lowest, coinciding with a phylotypic period that persisted well beyond the pharyngula ‘stage’. The trajectory culminated with elevated variation in a handful of fetal and perinatal characters, yielding an irregular hourglass pattern. Our study invites further quantification of ontogeny across diverse amniotes and thus challenges current ideas on the universality of developmental patterns.
Experience shapes accuracy in territorial decision-making in a poison frog
Authors: Sonnleitner Ria , Ringler Max , Loretto Matthias-Claudio , Ringler Eva
Published: May 2020

The trade-off between speed and accuracy affects many behavioural processes like predator avoidance, foraging and nest-site selection, but little is known about this trade-off relative to territorial behaviour. Some poison frogs are highly territorial and fiercely repel calling male intruders. However, attacks need to be conducted cautiously, as they are energetically costly and bear the risk of own injury or accidentally targeting the wrong individual. In this study, we investigated the speed–accuracy trade-off in the context of male territoriality during the breeding season in the brilliant-thighed poison frog,
Allobates femoralis
. In our experiment, we presented the call of an invisible ‘threatening’ intruder together with a visible ‘non-threatening’ intruder, using acoustic playback and a frog model, respectively. Contrary to our prediction, neither reaction time nor approach speed of the tested frogs determined the likelihood of erroneous attacks. However, younger individuals were more likely to attack the non-threatening model than older ones, suggesting that experience plays an essential role in identifying and distinguishing rivalling individuals in a territorial context.
Predicting collapse of complex ecological systems: quantifying the stability–complexity continuum
Authors: Pettersson Susanne , Savage Van M. , Nilsson Jacobi Martin
Published: May 2020

Dynamical shifts between the extremes of stability and collapse are hallmarks of ecological systems. These shifts are limited by and change with biodiversity, complexity, and the topology and hierarchy of interactions. Most ecological research has focused on identifying conditions for a system to shift from stability to any degree of instability—species abundances do not return to exact same values after perturbation. Real ecosystems likely have a continuum of shifting between stability and collapse that depends on the specifics of how the interactions are structured, as well as the type and degree of disturbance due to environmental change. Here we map boundaries for the extremes of strict stability and collapse. In between these boundaries, we find an intermediate regime that consists of single-species extinctions, which we call the extinction continuum. We also develop a metric that locates the position of the system within the extinction continuum—thus quantifying proximity to stability or collapse—in terms of ecologically measurable quantities such as growth rates and interaction strengths. Furthermore, we provide analytical and numerical techniques for estimating our new metric. We show that our metric does an excellent job of capturing the system's behaviour in comparison with other existing methods—such as May’s stability criteria or critical slowdown. Our metric should thus enable deeper insights about how to classify real systems in terms of their overall dynamics and their limits of stability and collapse.
The interplay of phenotypic variability and fitness in finite microbial populations
Authors: Levien Ethan , Kondev Jane , Amir Ariel
Published: May 2020

In isogenic microbial populations, phenotypic variability is generated by a combination of stochastic mechanisms, such as gene expression, and deterministic factors, such as asymmetric segregation of cell volume. Here we address the question: how does phenotypic variability of a microbial population affect its fitness? While this question has previously been studied for exponentially growing populations, the situation when the population size is kept fixed has received much less attention, despite its relevance to many natural scenarios. We show that the outcome of competition between multiple microbial species can be determined from the distribution of phenotypes in the culture using a generalization of the well-known Euler–Lotka equation, which relates the steady-state distribution of phenotypes to the population growth rate. We derive a generalization of the Euler–Lotka equation for finite cultures, which relates the distribution of phenotypes among cells in the culture to the exponential growth rate. Our analysis reveals that in order to predict fitness from phenotypes, it is important to understand how distributions of phenotypes obtained from different subsets of the genealogical history of a population are related. To this end, we derive a mapping between the various ways of sampling phenotypes in a finite population and show how to obtain the equivalent distributions from an exponentially growing culture. Finally, we use this mapping to show that species with higher growth rates in exponential growth conditions will have a competitive advantage in the finite culture.
Absolutely robust controllers for chemical reaction networks
Authors: Kim Jinsu , Enciso German
Published: May 2020

In this work, we design a type of controller that consists of adding a specific set of reactions to an existing mass-action chemical reaction network in order to control a target species. This set of reactions is effective for both deterministic and stochastic networks, in the latter case controlling the mean as well as the variance of the target species. We employ a type of network property called absolute concentration robustness (ACR). We provide applications to the control of a multisite phosphorylation model as well as a receptor–ligand signalling system. For this framework, we use the so-called deficiency zero theorem from chemical reaction network theory as well as multiscaling model reduction methods. We show that the target species has approximately Poisson distribution with the desired mean. We further show that ACR controllers can bring robust perfect adaptation to a target species and are complementary to a recently introduced antithetic feedback controller used for stochastic chemical reactions.
Extreme genomic volatility characterizes the evolution of the immunoglobulin heavy chain locus in cyprinodontiform fishes
Authors: Bradshaw William J. , Valenzano Dario Riccardo
Published: May 2020

The evolution of the adaptive immune system has provided vertebrates with a uniquely sophisticated immune toolkit, enabling them to mount precise immune responses against a staggeringly diverse range of antigens. Like other vertebrates, teleost fishes possess a complex and functional adaptive immune system; however, our knowledge of the complex antigen-receptor genes underlying its functionality has been restricted to a small number of experimental and agricultural species, preventing systematic investigation into how these crucial gene loci evolve. Here, we analyse the genomic structure of the immunoglobulin heavy chain (
IGH
) gene loci in the cyprinodontiforms, a diverse and important group of teleosts present in many different habitats across the world. We reconstruct the complete
IGH
loci of the turquoise killifish (
Nothobranchius furzeri
) and the southern platyfish (
Xiphophorus maculatus
) and analyse their
in vivo
gene expression, revealing the presence of species-specific splice isoforms of transmembrane
IGHM
. We further characterize the
IGH
constant regions of 10 additional cyprinodontiform species, including guppy, Amazon molly, mummichog and mangrove killifish. Phylogenetic analysis of these constant regions suggests multiple independent rounds of duplication and deletion of the teleost-specific antibody class
IGHZ
in the cyprinodontiform lineage, demonstrating the extreme volatility of
IGH
evolution. Focusing on the cyprinodontiforms as a model taxon for comparative evolutionary immunology, this work provides novel genomic resources for studying adaptive immunity and sheds light on the evolutionary history of the adaptive immune system.
Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France
Authors: Edouard S. , Colson P. , Melenotte C. , De Pinto F. , Thomas L. , La Scola B. , Million M. , Tissot-Dupont H. , Gautret P. , Stein A. , Brouqui P. , Parola P. , Lagier J.-C. , Raoult D. , Drancourt M.
Published: May 2020

An indirect immunofluorescent assay was developed in order to assess the serological status of 888 RT-PCR-confirmed COVID-19 patients (1,302 serum samples) and controls in Marseille, France. Incorporating an inactivated clinical SARS CoV-2 isolate as the antigen, the specificity of the assay was measured as 100% for IgA titre ≥ 1:200; 98.6% for IgM titre ≥ 1:200; and 96.3% for IgG titre ≥ 1:100 after testing a series of negative controls as well as 150 serums collected from patients with non-SARS-CoV-2 Coronavirus infection, non-Coronavirus pneumonia and infections known to elicit false-positive serology. Seroprevalence was then measured at 3% before a five-day evolution up to 47% after more than 15 days of evolution. We observed that the seroprevalence as well as the titre of specific antibodies were both significantly higher in patients with a poor clinical outcome than in patients with a favourable evolution. These data, which have to be integrated into the ongoing understanding of the immunological phase of the infection, suggest that serotherapy may not be a therapeutic option in patients with severe COVID-19 infection. The IFA assay reported here is useful for monitoring SARS-CoV-2 exposure at the individual and population levels.
Predicting the Growth and Trend of COVID-19 Pandemic using Machine Learning and Cloud Computing
Authors: Tuli Shreshth , Tuli Shikhar , Tuli Rakesh , Gill Sukhpal Singh
Published: May 2020

Abstract

The outbreak of COVID-19 Coronavirus, namely SARS-CoV-2, has created a calamitous situation throughout the world. The cumulative incidence of COVID-19 is rapidly increasing day by day. Machine Learning (ML) and Cloud Computing can be deployed very effectively to track the disease, predict growth of the epidemic and design strategies and policy to manage its spread. This study applies an improved mathematical model to analyse and predict the growth of the epidemic. An ML-based improved model has been applied to predict the potential threat of COVID-19 in countries worldwide. We show that using iterative weighting for fitting Generalized Inverse Weibull distribution, a better fit can be obtained to develop a prediction framework. This can be deployed on a cloud computing platform for more accurate and real-time prediction of the growth behavior of the epidemic. A data driven approach with higher accuracy as here can be very useful for a proactive response from the government and citizens. Finally, we propose a set of research opportunities and setup grounds for further practical applications. Predicted curves for some of the most affected countries can be seen at https://collaboration.coraltele.com/covid/.
Prolonged viral RNA shedding after COVID-19 symptom resolution in older convalescent plasma donors
Authors: Hartman William R , Hess Aaron S , Connor Joseph
Published: May 2020

Importance

The novel coronavirus, SARS-CoV-2, is responsible for a world-wide pandemic. While the medical community understands the mode of viral transmission, less is known about how long viral shedding occurs once viral symptoms have resolved.

Objective

To determine how long the SARS-CoV-2 remains detectable following self-reporting of viral symptom resolution.

Design

A cohort of 86 previously SARS-CoV-2 positive patients were re-tested for proof of viral recovery by nasal swab and nucleic acid amplification less than 28 days after self-reported symptom resolution. This study was approved by the University of Wisconsin Institutional Review Board.

Setting

A tertiary care center in a mid-size city utilizing a drive-through SAR-CoV-2 testing center.

Participants

86 previously confirmed SARS-CoV-2 positive individuals less than 28 days after self-reported resolution of symptoms evaluated as potential donors for COVID-19 convalescent plasma.

Intervention

Participants underwent nasopharyngeal sampling and subsequent nucleic acid amplification for SARS-CoV-2 genes.

Main Outcome

SARS-CoV-2 RNA in nasopharyngeal secretions detected by rtPCR.

Results

11/86 (13%) previously confirmed SARS-CoV-2 subjects were still positive at a median of 19 days (range 12-24 days) after symptom resolution. Older patients were more likely to be test-positive, and older positive patients had lower rtPCR CT values. Test-positive patients were not significantly different from test-negative patients with respect to days since symptom recovery.

Conclusions and Resolution

These results underscore the necessity of testing COVID-19 convalescent plasma donors less than 28 days after symptom resolution and suggests that COVID-19 positive patients may need to remain in quarantine beyond the recommended two weeks following “recovery.”

Trial Registration

n/a
COVID-19 Outbreak, Social Response, and Early Economic Effects: A Global VAR Analysis of Cross-Country Interdependencies
Authors: Milani Fabio
Published: May 2020

The COVID-19 pandemic underscored the importance of countries’ interconnections in understanding and reacting to the spread of the virus.

This paper uses a global model with a sample of 41 countries to study the interdependencies between COVID-19 health shocks, populations’ risk perceptions about the disease, and their social distancing responses; it also provides some early evidence about potential economic effects.

Social networks are a central component in understanding the international transmission.

We exploit a dataset on existing social connections across country borders, made available by Facebook, and show that social networks help explain not only the spread of the disease, but also cross-country spillovers in risk perceptions and in social behavior. Social distancing responses across countries are measured based on aggregated mobility tracking indicators, obtained from Google Mobility Reports.

We estimate a Global VAR (GVAR) model, which allows for endogeneity of each health, social, and economic, domestic variable, and for a dependence of domestic variables on country-specific foreign aggregates, which depend in turn on the matrix of social connections.

Our empirical results highlight the importance of cross-country interdependencies and social networks. Risk perceptions and social responses are affected by experiences abroad, with Italy and the U.S. playing large roles in our sample. The social distancing responses to domestic health shocks are heterogeneous across countries, but they share some similarities: they adjust only gradually and with delay, hence displaying adaptive behavior.

Early indicators are suggestive of unemployment consequences that vary widely across countries, depending on their labor market characteristics. Unemployment is particularly responsive to health shocks in the U.S. and Spain, while the fluctuations are attenuated almost everywhere else.
Stability of SARS-CoV-2 on environmental surfaces and in human excreta
Authors: Liu Yongjian , Li Tianyi , Deng Yongqiang , Liu Siyang , Zhang Dong , Li Hanping , Wang Xiaolin , Jia Lei , Han Jingwan , Bei Zhuchun , Zhou Yusen , Li Lin , Li Jingyun
Published: May 2020

At room temperature, SARS-CoV-2 was stable on environmental surfaces and remained viable up to 7 days on smooth surfaces. This virus could survive for several hours in feces and 3-4 days in urine.
SARS-CoV-2 Infection-Associated Hemophagocytic Lymphohistiocytosis: An autopsy series with clinical and laboratory correlation
Authors: Prilutskiy Andrey , Kritselis Michael , Shevtsov Artem , Yambayev Ilyas , Vadlamudi Charitha , Zhao Qing , Kataria Yachana , Sarosiek Shayna R. , Lerner Adam , Sloan J. Mark , Quillen Karen , Burks Eric J.
Published: May 2020

Background

A subset of COVID-19 patients exhibit clinical features of cytokine storm. However, clinicopathologic features diagnostic of hemophagocytic lymphohistiocytosis (HLH) have not been reported. Pathologic studies to date have largely focused on the pulmonary finding of diffuse alveolar damage (DAD). To this aim, we study the reticuloendothelial organs of four consecutive patients dying of COVID-19 and correlate with clinical and laboratory parameters to detect HLH.

Methods

Autopsies restricted to chest and abdomen were performed on four patients who succumbed to COVID-19. Spleen, liver, and multiple pulmonary hilar/mediastinal lymph nodes were sampled in all cases. Bone marrow was obtained by rib squeeze in a subset of cases. Routine H&E staining as well as immunohistochemical staining for CD163 was performed to detect hemophagocytosis. Clinical and laboratory results from pre-mortem blood samples were used to calculate H-scores.

Findings

All four cases demonstrated DAD within the lungs. Three of the four cases had histologic evidence of hemophagocytosis within pulmonary hilar/mediastinal lymph nodes. One case showed hemophagocytosis in the spleen but none showed hemophagocytosis in liver or bone marrow. Lymphophagocytosis was the predominant form of hemophagocytosis observed. One patient showed diagnostic features of HLH with an H-score of 217 while a second patient was likely HLH with a partial H-score of 145 due to missing triglyceride level. Both patients exhibited high fever and early onset rise in serum ferritin; however, neither bicytopenia, pancytopenia, nor hypofibrinogenemia were observed in either. The remaining two patients had H-scores of 131 and 96.

Interpretation

This is the first report of SARS-CoV-2 associated HLH. Identification of HLH in a subset of patients with severe COVID-19 will inform clinical trials of therapeutic strategies.
Carbomer-based Nano-Emulsion Adjuvant Enhances Dendritic Cell Cross-presentation via Lipid Body Formation Independent of Glycolysis
Authors: Lee Woojong , Kingstad-Bakke Brock , Paulson Brett , Larsen Autumn R. , Overmyer Katherine , Marinaik Chandranaik B. , Dulli Kelly , Toy Randall , Vogel Gabriela , Mueller Katherine P. , Tweed Kelsey , Walsh Alex J. , Russell Jason , Saha Krishanu , Reyes Leticia , Skala Melissa C. , Sauer John-Demian , Shayakhmetov Dmitry M. , Coon Joshua , Roy Krishnendu , Suresh M.
Published: May 2020

Here, we report that a carbomer-based adjuvant, Adjuplex® (ADJ), stimulated robust CD8 T-cell responses to subunit antigens by modulating multiple steps in the cytosolic pathway of cross-presentation, and afforded effective immunity against virus and intracellular bacteria. Cross-presentation induced by TLR agonists requires a critical switch to anabolic metabolism, but ADJ enhanced cross presentation without this metabolic switch in DCs and NLRP3-driven caspase 1 activity. Instead, ADJ induced in DCs, an unique metabolic state, typified by dampened oxidative phosphorylation and basal levels of glycolysis. In the absence of increased glycolytic flux, induction of ROS and lipid bodies (LBs) and alterations in LB composition mediated by ADJ were critical for DC cross-presentation. These findings challenge the prevailing metabolic paradigm by suggesting that DCs can perform effective DC cross-presentation, independent of glycolysis to induce robust T cell-dependent protective immunity to intracellular pathogens. These findings have implications in the rational development of novel adjuvants.
A Research on the Results of Viral Nucleic Acid Tests and CT Imaging Variation of Patients with COVID-19
Authors: Xu Meng , Liu Xun , Su Chuhong , Zeng Yuping , Zhang Jinqian , Li Xuwen , Liu Guirong , Xie Jinjun , Liu Hongyong , Jie Yusheng
Published: May 2020

Background

Coronavirus disease 2019 (COVID-19) has become a global health problem. We aim to investigate the changes in the results of viral nucleic acid tests on pharyngeal swabs and feces of patients with COVID-19 and CT imaging of lungs as the disease progresses.

Methods

Seven patients with COVID-19 in the third affiliated hospital of Sun Yat-sen University Yuedong Hospital were retrospectively enrolled with clinical features, including imaging staging, and performance characteristics of viral nucleic acid test results of pharyngeal swabs and feces. The dynamic changes of these features were observed during hospitalization, and therapeutic effect and prognosis of patients were evaluated.

Results

The results of seven cases with COVID-19 were positive for viral nucleic acid tests on pharyngeal swabs early after the onset of symptoms, and then turned negative; while the results of viral nucleic acid tests on feces were persistently positive in the mid-term clinical treatment and recovery period. And the viral nucleic acid test results were capricious in three cases. Pulmonary CT imaging showed characteristic changes in early, advanced and recovery phases.

Conclusion

The application of viral nucleic acid detection and pulmonary CT imaging can be used for screening of suspected cases. Fecal nucleic acid test should be recommended as the reference of discharge standard, in order to minimize the risk of transmission from digestive tract.
Characteristics and outcomes of pregnant women hospitalised with confirmed SARS-CoV-2 infection in the UK: a national cohort study using the UK Obstetric Surveillance System (UKOSS)
Authors: Knight Marian , Bunch Kathryn , Vousden Nicola , Morris Eddie , Simpson Nigel , Gale Chris , O’Brien Patrick , Quigley Maria , Brocklehurst Peter , Kurinczuk Jennifer J
Published: May 2020

Objective

To describe a national cohort of pregnant women hospitalised with SARS-CoV-2 infection in the UK, identify factors associated with infection and describe outcomes, including transmission of infection, for mother and infant.

Design

Prospective national population-based cohort study using the UK Obstetric Surveillance System (UKOSS).

Setting

All 194 obstetric units in the UK

Participants

427 pregnant women admitted to hospital with confirmed Sars-CoV-2 infection between 01/03/2020 and 14/04/2020. 694 comparison women who gave birth between 01/11/2017 and 31/10/2018.

Main outcome measures

Incidence of maternal hospitalisation, infant infection. Rates of maternal death, level 3 critical care unit admission, preterm birth, stillbirth, early neonatal death, perinatal death; odds ratios for infected versus comparison women.

Results

Estimated incidence of hospitalisation with confirmed SARS-CoV-2 in pregnancy 4.9 per 1000 maternities (95%CI 4.5-5.4). The median gestation at symptom onset was 34 weeks (IQR 29-38). Black or other minority ethnicity (aOR 4.49, 95%CI 3.37-6.00), older maternal age (aOR 1.35, 95%CI 1.01-1.81 comparing women aged 35+ with those aged 30-34), overweight and obesity (aORs 1.91, 95%CI 1.37-2.68 and 2.20, 95%CI 1.56-3.10 respectively compared to women with a BMI<25kg/m2) and pre-existing comorbidities (aOR 1.52, 95%CI 1.12-2.06) were associated with admission with SARS-CoV-2 during pregnancy. 247 women (58%) gave birth or had a pregnancy loss; 180 (73%) gave birth at term. 40 (9%) hospitalised women required respiratory support. Twelve infants (5%) tested positive for SARS-CoV-2 RNA, six of these infants within the first 12 hours after birth.

Conclusions

The majority of pregnant women hospitalised with SARS-CoV-2 were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes and transmission of SARS-CoV-2 to infants was uncommon. The strong association between admission with infection and black or minority ethnicity requires urgent investigation and explanation.

Study Registration

ISRCTN 40092247
SELF-POLICING COVID-19 AND CIVIC RESPONSIBILITIES IN LAGOS METROPOLIS, NIGERIA
Authors: Ilori Ayomide
Published: May 2020

This study investigated self-policing COVID-19 and civic responsibilities in Lagos Metropolis, Nigeria adopting an online qualitative interview due to the current lockdown that denied field (face to face) interview. Fifty out of the feedbacks from the online interview were picked randomly to arrive at the conclusion of this study. The feedbacks suggested that there is adequate awareness of the COVID-19 pandemic among the people living in Lagos Metropolis, Nigeria and that they are following the directives of federal and state governments in an effort to reduce the community transmission of the infectious diseases. However, the ban on public gatherings and movements has made it impossible for many homes to meet their basic needs especially feeding. The government provided palliatives have also been largely insufficient to cater for the vulnerable. There could be a crisis (such as hunger) and the breakdown of law and order if the government does not increase their capacity to mitigate the hardship which the ongoing lockdown has imposed on the people.
Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers
Authors: Lee Ivan T. , Nakayama Tsuguhisa , Wu Chien-Ting , Goltsev Yury , Jiang Sizun , Gall Phillip A. , Liao Chun-Kang , Shih Liang-Chun , Schürch Christian M. , McIlwain David R. , Chu Pauline , Borchard Nicole A. , Zarabanda David , Dholakia Sachi S. , Yang Angela , Kim Dayoung , Kanie Tomoharu , Lin Chia-Der , Tsai Ming-Hsui , Phillips Katie M. , Kim Raymond , Overdevest Jonathan B. , Tyler Matthew A. , Yan Carol H. , Lin Chih-Feng , Lin Yi-Tsen , Bau Da-Tian , Tsay Gregory J. , Patel Zara M. , Tsou Yung-An , Tai Chih-Jaan , Yeh Te-Huei , Hwang Peter H. , Nolan Garry P. , Nayak Jayakar V. , Jackson Peter K.
Published: May 2020

We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.
Use of excess mortality associated with the COVID-19 epidemic as an epidemiological surveillance strategy - preliminary results of the evaluation of six Brazilian capitals
Authors: Freitas André Ricardo Ribas , de Medeiros Nicole Montenegro , Frutuoso Livia Carla Vinhal , Beckedorff Otto Albuquerque , de Martin Lucas Mariscal Alves , de Medeiros Coelho Marcela Montenegro , de Freitas Giovanna Gimenez Souza , Lemos Daniele Rocha Queiróz , Cavalcanti Luciano Pamplona de Góes
Published: May 2020

In early 2020, the World Health Organization (WHO) recognized the pandemic situation of the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), which causes Coronavirus Disease-2019 (COVID-19). In Brazil by the end of April 2020, another 110 thousand cases and 5,000 deaths had been confirmed. The scarcity of laboratory resources and overload of the care network, added to the broad clinical spectrum of the disease, can make it difficult to capture all mortality from this disease through epidemiological surveillance based on individual notification of cases. The aim of this study was to evaluate the excess of deaths in Brazilian capitals with the highest incidence of COVID-19, as a way of validating the method, we also evaluated a capital with low incidence.

We assessed weekly mortality from all causes during the year 2020, up to the epidemiological week 17, compared with the previous year. The data were obtained through the National Civil Registry Information Center (CNIRC, acronym in Portuguese). We estimate the expected mortality and the 95% confidence interval by projecting the observed mortality in 2019 for the population of 2020.

In the five capitals with the highest incidences it was possible to identify excess deaths in the pandemic period, the age group most affected were those over 60 years old, 31% of the excess deaths occurred in the population between 20 and 59 years old. There was a strong correlation (r = 0.94) between the excess of deaths in each city and the number of deaths confirmed by epidemiological surveillance. There was no excess of deaths in the capital with the lowest incidence, nor among the population under 20 years old. We estimate that epidemiological surveillance managed to capture only 52% of all mortality associated with the COVID-19 pandemic in the cities studied.

Considering the simplicity of the method, its low cost and reliability for assessing the real burden of the disease, we believe that the assessment of excess mortality associated with the COVID-19 pandemic should be widely used as a complementary tool to regular epidemiological surveillance and its use should be encouraged by WHO.
Epidemics, Air Travel, and Elimination in a Globalized World: The Case of Measles
Authors: Truelove Shaun , Mier-y-Teran-Romero Luis , Gastanaduy Paul , Walker Allison Taylor , Berro Andre , Lessler Justin , Johansson Michael A.
Published: May 2020

Although the United States (U.S.) declared measles eliminated in 2000, so long as measles circulates globally, continued importations will trigger sporadic U.S. outbreaks. The United States is highly connected to the rest of the world, and importations occur largely as a result of air travel by U.S. residents and international visitors. We developed a model to assess the risk of measles virus importation from Europe, Asia, and Africa through air travel. We projected 308 (95% prediction interval, 151-518) total measles cases imported from 66 countries during 2006-2015; 290 importations were reported. The model projected a spike in importation risk from Israel during October 2018, coincident with large, importation-triggered outbreaks in New York and New Jersey. Our model shows U.S. importation risk primarily originates from European and Asian countries. Models such as this inform preemptive actions to mitigate infectious disease threats, but only if we prioritize global surveillance and data sharing.
Test-retest reliability of force plate-derived measures of reactive stepping
Authors: Saumur Tyler M. , Mathur Sunita , Nestico Jacqueline , Perry Stephen D. , Mochizuki George , Mansfield Avril
Published: May 2020

Background

Characterizing reactive stepping is important to describe the response’s effectiveness. Measures of reactive stepping related to step initiation, execution, and termination phases have been frequently reported to characterize reactive balance control. However, the test-retest reliability of these measures are unknown.

Research questions

What is the between- and within-session test-retest reliability of various force plate-derived measures of reactive stepping?

Methods

Nineteen young, healthy adults responded to 6 small (~8-10% of body weight) and 6 large perturbations (~13-15% of body weight) using an anterior lean-and-release system. Tests were conducted on two visits separated by at least two days. Participants were instructed to recover balance in as few steps as possible. Step onset, foot-off, swing, and restabilization times were extracted from force plates. Relative test-retest reliability was determined through intraclass correlation coefficients (ICCs) and 95% confidence intervals (CIs). Absolute test-retest reliability was assessed using the standard error of the measurement (SEM).

Results

Foot-off and swing times had the highest between- and within-session test-retest reliabilities regardless of perturbation size (between-session ICC=0.898–0.942; within-session ICC=0.455–0.753). Conversely, step onset and restabilization time had lower ICCs and wider CIs (between-session ICC=0.495–0.825; within-session ICC=−0.040–0.174). Between-session test-retest reliability was higher (ICC=0.495-0.942) for all measures than within-session test-retest reliability (ICC=−0.040–0.753). SEMs were low (3–10% of mean) for all measures, except time to restabilization (SEM=15-20% of mean), indicating good absolute reliability.

Significance

These findings suggest multiple baseline sessions are needed for measuring restabilization and step onset times. The SEMs provide an index for measuring meaningful change due to an intervention.
Eating to dare - Nutrition impacts human risky decision and related brain function
Authors: Liu Lu , Artigas Sergio Oroz , Ulrich Anja , Tardu Jeremy , Mohr Peter N. C. , Wilms Britta , Koletzko Berthold , Schmid Sebastian M. , Park Soyoung Q.
Published: May 2020

Macronutrient composition modulates plasma amino acids that are precursors of neurotransmitters and can impact brain function and decisions. Neurotransmitter serotonin has been shown to regulate not only food intake, but also economic decisions. We investigated whether an acute nutrition-manipulation inducing plasma tryptophan fluctuation affects brain function, thereby affecting risky decisions. Breakfasts differing in carbohydrate/protein ratios were offered to test changes in risky decision making while metabolic and neural dynamics were tracked. We identified that a high-carbohydrate/protein meal increased plasma tryptophan which mapped to individual risk propensity changes. Moreover, the meal-driven fluctuation in tryptophan and risk propensity changes were modulated by individual difference in body fat mass. Using fMRI, we further identified activation in the parietal lobule during risk-processing, of which activities 1) were correlated with the risk propensity changes in decision making, 2) were sensitive to the tryptophan fluctuation, and 3) were modulated by individual’s body fat mass. Furthermore, the activity in the parietal lobule positively mediated the tryptophan-fluctuation to risk-propensity-changes relationship. Our results provide evidence for a personalized nutrition-driven modulation on human risky decisions and its metabolic and neural mechanisms.
Antibiotics in microbial communities: an ecological frame of resistance
Authors: Letten Andrew D. , Hall Alex , Levine Jonathan
Published: May 2020

There is growing awareness that our ability to tackle antibiotic resistance is limited by a lack of mechanistic understanding of the communities in which resistant microbes are embedded. The widespread coexistence of resistant and sensitive bacteria in microbial systems presents an especially frustrating paradox. Recent advances in ecological coexistence theory offer a powerful framework to probe the mechanisms regulating intra- and inter-specific coexistence, but the significance of this body of theory to the problem of antimicrobial resistance has been largely overlooked. In this Perspectives article, we draw on emerging ecological theory to illustrate how changes in both competitive ability and niche overlap are critical for understanding costs of resistance and the persistence of pathogens in microbial systems. We then show how trade-offs in resource acquisition strategies can have counter-intuitive consequences for the coexistence of resistant and susceptible genotypes in variable environments. These insights highlight numerous opportunities for innovative experimental and theoretical research into antibiotic resistance in the microbiome.
Metabolomic signatures of coral bleaching history
Authors: Roach Ty N.F. , Dilworth Jenna , Christian Martin H. , Jones A. Daniel , Quinn Robert , Drury Crawford
Published: May 2020

Coral bleaching, a process where corals expel their photosynthetic symbionts, has a profound impact on the health and function of coral reefs. As global ocean temperatures continue to rise, bleaching poses the greatest threat to coral reef ecosystems. Here, untargeted metabolomics was used to analyze the biochemicals in pairs of adjacent corals from a patch reef in Kāne‘ohe Bay, Hawai‘i, where one colony in the pair bleached (in 2015) and recovered while the other did not bleach. There was a strong metabolomic signature of prior bleaching history four years after recovery found in both the host and its algal symbionts. Machine learning analysis determined that the strongest metabolite drivers of the difference in bleaching phenotype were a group of betaine lipids. Those with saturated fatty acids were significantly enriched in thermally tolerant corals and those with longer, unsaturated and diacyl forms were enriched in historically bleached corals. Host immune response molecules, Lyso-PAF and PAF, were also altered by bleaching history and were strongly correlated with symbiont community and algal-derived metabolites suggesting a role of coral immune modulation in symbiont choice and bleaching response. To validate these findings, we tested a separatein situset of corals and were able to predict the bleaching phenotype with 100% accuracy. Furthermore, corals subjected to an experimental temperature stress had strong phenotype-specific responses in all components of the holobiont, which served to further increase the differences between historical bleaching phenotypes. Thus, we show that natural bleaching susceptibility is simultaneously manifested in the biochemistry of the coral animal and the algal symbiont and that this bleaching history results in different physiological responses to temperature stress. This work provides insight into the biochemical mechanisms involved in coral bleaching and presents a valuable new tool for resilience-based reef restoration.
CEN-tools: An integrative platform to identify the ‘contexts’ of essential genes
Authors: Sharma Sumana , Dincer Cansu , Weidemüller Paula , Wright Gavin J , Petsalaki Evangelia
Published: May 2020

I.

An emerging theme from large-scale genetic screens that identify genes essential for fitness of a cell, is that essentiality of a given gene is highly context-specific and depends on a number of genetic and environmental factors. Identification of such contexts could be the key to defining the function of the gene and also to develop novel therapeutic interventions. Here we present CEN-tools (Context-specificEssentialityNetwork-tools), a website and an accompanying python package, in which users can interrogate the essentiality of a gene from large-scale genome-scale CRISPR screens in a number of biological contexts including tissue of origin, mutation profiles, expression levels, and drug response levels. We show that CEN-tools is suitable for both the systematic identification of genetic dependencies as well as for targeted queries into the dependencies of specific user-selected genes. The associations between genes and a given context within CEN-tools are represented as dependency networks (CENs) and we demonstrate the utility of these networks in elucidating novel gene functions. In addition, we integrate the dependency networks with existing protein-protein interaction networks to reveal context-dependent essential cellular pathways in cancer cells. Together, we demonstrate the applicability of CEN-tools in aiding the current efforts to define the human cellular dependency map.
Sensorimotor hallucinations in Parkinson’s disease
Authors: Bernasconi Fosco , Blondiaux Eva , Potheegadoo Jevita , Stripeikyte Giedre , Pagonabarraga Javier , Bejr-Kasem Helena , Bassolino Michela , Akselrod Michel , Martinez-Horta Saul , Sampedro Fred , Hara Masayuki , Horvath Judit , Franza Matteo , Konik Stéphanie , Bereau Matthieu , Ghika Joseph-André , Burkhard Pierre R. , Van De Ville Dimitri , Faivre Nathan , Rognini Giulio , Krack Paul , Kulisevsky Jaime , Blanke Olaf
Published: May 2020

Hallucinations in Parkinson’s disease (PD) are one of the most disturbing non-motor symptoms, affect half of the patients, and constitute a major risk factor for adverse clinical outcomes such as psychosis and dementia. Here we report a robotics-based approach, enabling the induction of a specific clinically-relevant hallucination (presence hallucination, PH) under controlled experimental conditions and the characterization of a PD subgroup with enhanced sensorimotor sensitivity for such robot-induced PH. Using MR-compatible robotics in healthy participants and lesion network mapping analysis in neurological non-PD patients, we identify a fronto-temporal network that was associated with PH. This common PH-network was selectively disrupted in a new and independent sample of PD patients and predicted the presence of symptomatic PH. These robotics-neuroimaging findings determine the behavioral and neural mechanisms of PH and reveal pathological cortical sensorimotor processes of PH in PD, identifying a more severe form of PD associated with psychosis and cognitive decline.
HCR-FlowFISH: A flexible CRISPR screening method to identify cis-regulatory elements and their target genes
Authors: Reilly SK , Gosai SJ , Gutierrez A , Ulirsch JC , Kanai M , Berenzy D , Kales S , Butler GB , Gladden-Young A , Finucane HK , Sabeti PC , Tewhey R
Published: May 2020

CRISPR screens for cis-regulatory elements (CREs) have shown unprecedented power to endogenously characterize the non-coding genome. To characterize CREs we developed HCR-FlowFISH (Hybridization Chain Reaction Fluorescent In-Situ Hybridization coupled with Flow Cytometry), which directly quantifies native transcripts within their endogenous loci following CRISPR perturbations of regulatory elements, eliminating the need for restrictive phenotypic assays such as growth or transcript-tagging. HCR-FlowFISH accurately quantifies gene expression across a wide range of transcript levels and cell types. We also developed CASA (CRISPR Activity Screen Analysis), a hierarchical Bayesian model to identify and quantify CRE activity. Using >270,000 perturbations, we identified CREs forGATA1, HDAC6, ERP29, LMO2, MEF2C, CD164, NMU, FEN1and theFADSgene cluster. Our methods detect subtle gene expression changes and identify CREs regulating multiple genes, sometimes at different magnitudes and directions. We demonstrate the power of HCR-FlowFISH to parse genome-wide association signals by nominating causal variants and target genes.
Recognition memory via repetition suppression in mouse hippocampal dorsal CA2 pyramidal neurons expressing the vasopressin 1b receptor
Authors: Cymerblit-Sabba Adi , Stackmann Michelle , Avram Sarah K. Williams , Granovetter Michael C. , Cliz Nicholas I. , Pereira Francisco , Smith Adam S. , Song June , Lee Heon-Jin , Young W. Scott
Published: May 2020

Recognition memory, often compromised in psychiatric disorders, is a major component of declarative memory, which permits the realization that an event, object or social subject has been previously encountered. The CA2 region of the dorsal hippocampus (dCA2) is involved in social memory and responds to novel objects, in time and space. However, it remains unclear how these neurons encode either social or inanimate object recognition. Here, we show that in dCA2, encoding of social recognition memory entails suppression of pyramidal neurons’ activity leading to a sparse representation of the familiar conspecific. We discuss the neural coding scheme by which dCA2 pyramidal neurons contribute to social memory.