bluuebunny/crossref_metadata_2025 huggingface dataset:
Who goes there? Social surveillance as a response to intergroup conflict in a primitive termite
Authors: Thompson Faye J. , Hunt Kingsley L. , Wright Kallum , Rosengaus Rebeca B. , Cole Erin L. , Birch Graham , Maune Avery L. , Cant Michael A.
Published: July 2020

Intergroup conflict has been suggested as a major force shaping the evolution of social behaviour in animal groups. A long-standing hypothesis is that groups at risk of attack by rivals should become more socially cohesive, to increase resilience or protect against future attack. However, it is usually unclear how cohesive behaviours (such as grooming or social contacts) function in intergroup conflict. We performed an experiment in which we exposed young colonies of the dampwood termite,
Zootermopsis angusticollis
, to a rival colony while preventing physical combat with a permeable barrier. We measured social contacts, allogrooming and trophallaxis before, during and after exposure. Termites showed elevated rates of social contacts during exposure to a rival compared to the pre-exposure phase, but rates returned to pre-exposure levels after colonies were separated for 9 days. There was evidence of a delayed effect of conflict on worker trophallaxis. We suggest that social contacts during intergroup conflict function as a form of social surveillance, to check individual identity and assess colony resource holding potential. Intergroup conflict may increase social cohesion in both the short and the long term, improving the effectiveness of groups in competition.
An experimental test of parasite adaptation to common versus rare host genotypes
Authors: Gibson Amanda K. , White P. Signe , Penley McKenna J. , de Roode Jacobus C. , Morran Levi T.
Published: July 2020

A core hypothesis in coevolutionary theory proposes that parasites adapt to specifically infect common host genotypes. Under this hypothesis, parasites function as agents of negative frequency-dependent selection, favouring rare host genotypes. This parasite-mediated advantage of rarity is key to the idea that parasites maintain genetic variation and select for outcrossing in host populations. Here, we report the results of an experimental test of parasite adaptation to common versus rare host genotypes. We selected the bacterial parasite
Serratia marcescens
to kill
Caenorhabdiis elegans
hosts in uneven mixtures of host genotypes. To examine the effect of commonness itself, independent of host identity, each of four host genotypes was represented as common or rare in experimental host mixtures. After experimental selection, we evaluated a parasite line's change in virulence—the selected fitness trait—on its rare and common host genotypes. Our results were consistent with a slight advantage for rare host genotypes: on average, parasites lost virulence against rare genotypes but not against common genotypes. The response varied substantially, however, with distinct patterns across host genotype mixtures. These findings support the potential for parasites to impose negative frequency-dependent selection, while emphasizing that the cost of being common may vary with host genotype.
Crop production in the USA is frequently limited by a lack of pollinators
Authors: Reilly J. R. , Artz D. R. , Biddinger D. , Bobiwash K. , Boyle N. K. , Brittain C. , Brokaw J. , Campbell J. W. , Daniels J. , Elle E. , Ellis J. D. , Fleischer S. J. , Gibbs J. , Gillespie R. L. , Gundersen K. B. , Gut L. , Hoffman G. , Joshi N. , Lundin O. , Mason K. , McGrady C. M. , Peterson S. S. , Pitts-Singer T. L. , Rao S. , Rothwell N. , Rowe L. , Ward K. L. , Williams N. M. , Wilson J. K. , Isaacs R. , Winfree R.
Published: July 2020

Most of the world's crops depend on pollinators, so declines in both managed and wild bees raise concerns about food security. However, the degree to which insect pollination is actually limiting current crop production is poorly understood, as is the role of wild species (as opposed to managed honeybees) in pollinating crops, particularly in intensive production areas. We established a nationwide study to assess the extent of pollinator limitation in seven crops at 131 locations situated across major crop-producing areas of the USA. We found that five out of seven crops showed evidence of pollinator limitation. Wild bees and honeybees provided comparable amounts of pollination for most crops, even in agriculturally intensive regions. We estimated the nationwide annual production value of wild pollinators to the seven crops we studied at over $1.5 billion; the value of wild bee pollination of all pollinator-dependent crops would be much greater. Our findings show that pollinator declines could translate directly into decreased yields or production for most of the crops studied, and that wild species contribute substantially to pollination of most study crops in major crop-producing regions.
The Outcome of COVID-19 Patients with Acute Myocardial Infarction
Authors: Tamimi Hassan Al , Alhamad Yasser , Khazaal Fadi , ElHassan Mowahib , AlBinali Hajar , Arabi Abdul rahman , Al-Qahtani Awad , Asaad Nidal , Al-Hijji Mohammed , Hamid Tahir , Rafie Ihsan , Omrani Ali , Kaabi Saad Al , Alkhal Abdullatif , Maslamani Muna Al , Ali Mohamed , Alkhani Murad , AlNesf Mariam , Jalala Salem Abu , Arafa Salaheddine , ElSousy Reem , Tamimi Omar Al , Soaly Ezeldine , Khalil Charbel Abi , Suwaidi Jassim Al
Published: July 2020

Objectives

Coronavirus Disease 2019 (COVID-19) is a rapidly expanding global pandemic resulting in significant morbidity and mortality. COVID-19 patients may present with acute myocardial infarction (AMI). The aim of this study is to conduct detailed analysis on patients with AMI and COVID-19.

Methods

We included all patients admitted with AMI and actively known or found to be COVID-19 positive by PCR between the 4th February 2020 and the 11th June 2020 in the State of Qatar. Patients were divided into ST-elevation myocardial infarction (STEMI) and Non-STE (NSTEMI).

Results

There were 68 patients (67 men and 1 woman) admitted between the 4th of February 2020 and the 11th of June 2020 with AMI and COVID-19. The mean age was 49.1±9 years, 46 patients had STEMI and 22 had NSTEMI. 38% had diabetes mellitus, 31% had hypertension, 16% were smokers, 13% had dyslipidemia, and 14.7% had prior cardiovascular disease. Chest pain and dyspnea were the presenting symptoms in 90% and 12% of patients, respectively. Fever (15%) and cough (15%) were the most common COVID-19 symptoms, while the majority had no viral symptoms. Thirty-nine (33 STEMI and 6 NSTEMI) patients underwent coronary angiography, 38 of them had significant coronary disease. In-hospital MACE was low; 1 patient developed stroke and 2 died.

Conclusion

Contrary to previous small reports, in-hospital adverse events were low in this largest cohort of COVID-19 patients presenting with AMI. We hypothesize patient’s demographics and profile including younger age contributed to these findings. Further studies are required to confirm this observation.

Key questions

What is already known on this subject?

COVID-19 patients may present with acute myocardial infarction (AMI).

What might this study add?

Contrary to previous small reports, most COVID-19 patients presenting with AMI have significant obstructive coronary artery disease and favorable in-hospital outcome.

How might this impact on clinical practice?

COVID-19 patients presenting with AMI should be treated according to the standard practice.
Incorporating human mobility data improves forecasts of Dengue fever in Thailand
Authors: Kiang Mathew V , Santillana Mauricio , Chen Jarvis T , Onnela Jukka-Pekka , Krieger Nancy , Engø-Monsen Kenth , Ekapirat Nattwut , Areechokchai Darin , Prempree Preecha , Maude Richard J. , Buckee Caroline O
Published: July 2020

Over 390 million people worldwide are infected with dengue fever each year. In the absence of an effective vaccine for general use, national control programs must rely on hospital readiness and targeted vector control to prepare for epidemics, so accurate forecasting remains an important goal. Many dengue forecasting approaches have used environmental data linked to mosquito ecology to predict when epidemics will occur, but these have had mixed results. Conversely, human mobility, an important driver in the spatial spread of infection, is often ignored. Here we compare time-series forecasts of dengue fever in Thailand, integrating epidemiological data with mobility models generated from mobile phone data. We show that long-distance connectivity is correlated with dengue incidence at forecasting horizons of up to three months, and that incorporating mobility data improves traditional time-series forecasting approaches. Notably, no single model or class of model always outperformed others. We propose an adaptive, mosaic forecasting approach for early warning systems.
Incidence, risk factors and impact of seasonal influenza in pregnancy: A national cohort study
Authors: Vousden Nicola , Bunch Kathryn , Knight Marian ,   the UKOSS influenza Co-Investigators Group
Published: July 2020

Background

Pregnant women are particularly vulnerable to severe infection from influenza resulting in poor neonatal outcomes. The majority of evidence relates to pandemic 2009 A/H1N1 influenza. The objective of this study was to describe the characteristics and outcomes of pregnant women hospitalised with seasonal influenza.

Methods

This national, prospective, observational cohort study used the UK Obstetric Surveillance System (UKOSS) to identify all pregnant women admitted to hospital between 01/11/2016 and 31/10/2018 with laboratory confirmed influenza together with a comparison group of pregnant women. Baseline characteristics, immunisation status, maternal and perinatal outcomes were compared.

Results

There were 405 women admitted to hospital with laboratory confirmed influenza in pregnancy: 2.7 per 10,000 maternities. Compared to 694 comparison women, women with influenza were less likely to be professionally employed (aOR 0.59, 95%CI 0.39-0.89) or immunised in the relevant season (aOR 0·59, 0·39-0·89) and more likely to have asthma (aOR 2.42, 1.30-4.49) or have had a previous pregnancy complication (aOR 2·47, 1·33-4·61). They were more likely to be admitted to intensive care (aOR 21.3, 2.78-163.1) and to have a caesarean birth (aOR 1·42, 1·02-1.98). Their babies were more likely to be admitted to neonatal intensive care (aOR 1.86, 1·01-3·42).

Conclusions

Immunisation reduces the risk of hospitalisation with influenza in pregnancy which is associated with increased risk of morbidity for both the mother and baby. There is a continued need to increase awareness of safety and effectiveness of immunisation in pregnancy and provision within antenatal care settings, especially for high risk groups.

Key points

The incidence of hospital admission with seasonal influenza in pregnancy in the UK is 2.7 per 10,000 maternities. Lack of immunisation increases risk of hospitalisation. Influenza in pregnancy increases risk of caesarean birth and neonatal admission to intensive care.
Accounting for body mass effects in the estimation of field metabolic rates from body acceleration
Authors: Byrnes Evan E. , Lear Karissa O. , Brewster Lauran R. , Whitney Nicholas M. , Smukall Matthew J. , Armstrong Nicola J. , Gleiss Adrian C.
Published: July 2020

Life history, reproduction, and survival are fundamentally linked to energy expenditure and acquisition. Dynamic Body Acceleration (DBA), measured through animal-attached data-loggers or transmitters, has emerged as a powerful method for estimating field metabolic rates of free-ranging individuals. After using respirometry to calibrate oxygen consumption ratewith DBA in captive settings, predictive models can be applied to DBA data collected from free-ranging individuals. However, laboratory calibrations are generally performed on a narrow size range of animals, which may introduce biases when predictive models are applied to differently sized individuals in the field. Here, we tested the influence of scale effects on the ability of a single predictive model to predictover a range of body sizes. We performed respirometry experiments with individuals spanning one order of magnitude in body mass (1.74–17.15 kg) and used a two-step modelling process to assess the intra-specific scale dependence of the-DBA relationship and incorporate such dependencies into the covariates ofpredictive models. The final predictive model showed scale dependence; the slope of the-DBA relationship was strongly allometric (M1.55), whereas the intercept term scaled closer to isometry (M1.08). Using bootstrapping and simulations, we tested the performance of this covariate-corrected model against commonly used methods of accounting for mass effects on the-DBA relationship and found lowest error and bias in the covariate-corrected approach. The strong scale dependence of the-DBA relationship indicates that caution must be exercised when models developed using one size class are applied to individuals of different sizes.

Summary statement

The relationship between oxygen consumption rate and dynamic body acceleration is allometrically dependent, and models incorporate different slope and intercept scaling rates estimate metabolic rates more accurately than mass-specific approaches.
Therapeutic use of cannabis, cannabis-derived products and synthetic cannabinoids for rheumatoid arthritis: Protocol for a systematic review
Authors: Schulze Clara , Durán Josefina , Bravo-Jeria Rocío , Verdugo-Paiva Francisca , Morel Macarena , Rada Gabriel
Published: July 2020

OBJECTIVE

To assess the therapeutic effects of cannabis, cannabis-derived products and synthetic cannabinoids for rheumatoid arthritis.

DESIGN

This is the protocol of a systematic review. DATA SOURCES: Searches will be conducted in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries, grey literature and in a centralized repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS

We will include randomized controlled trials evaluating therapeutic use of cannabis, cannabis-derived products and synthetic cannabinoids for rheumatoid arthritis. Our primary interest will be in trials comparing the intervention with placebo or no treatment (intervention plus optimal treatment vs placebo plus optimal treatment or optimal treatment alone) in patients receiving optimal treatment for rheumatoid arthritis. Optimal treatment will be defined as disease modifying anti-rheumatic drugs. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of the evidence for each outcome.

ETHICS AND DISSEMINATION

The Scientific Ethics Committee of the Pontificia Universidad Católica de Chile granted ethical exemption for the realization of this study. Results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media and will be sent to relevant international organizations discussing this topic.
AutoSEIR: Accurate Forecasting from Real-time Epidemic Data Using Machine Learning
Authors: Rizzo Stefano Giovanni , Vantini Giovanna , Saad Mohamad , Chawla Sanjay
Published: July 2020

Since the SARS-CoV-2 virus outbreak has been recognized as a pandemic on March 11, 2020, several models have been proposed to forecast its evolution following the governments’ interventions. In particular, the need for fine-grained predictions, based on real-time and fluctuating data, has highlighted the limitations of traditional SEIR models and parameter fitting, encouraging the study of new models for greater accuracy. In this paper we propose a novel approach to epidemiological parameter fitting and epidemic forecasting, based on an extended version of the SEIR compartmental model and on an auto-differentiation technique for partially observable ODEs (Ordinary Differential Equations). The results on publicly available data show that the proposed model is able to fit the daily cases curve with greater accuracy, obtaining also a lower forecast error. Furthermore, the forecast accuracy allows to predict the peak with an error margin of less than one week, up to 50 days before the peak happens.
Impact of climatic parameters on COVID-19 pandemic in India: analysis and prediction
Authors: Deyal Namrata , Tiwari Vipin , Bisht Nandan S.
Published: July 2020

The COVID-19 is spreading very fast globally and various factors of it have to be analysed. The aim of this study is to analyze the effect of climatic parameters (Average Temperature (AT), Atmospheric Pressure (AP), Relative Humidity (RH), Solar Radiation (SR) and Wind Speed (WS)) on the COVID-19 epidemic during 25 March 2020 to 15 June 2020 in most affected states of India i.e. Maharashtra, Delhi and Tamilnadu. We quantitatively establish the correlation between these parameters by using Kendall & Spearman rank correlation test. The results indicate that the numbers of cases are highly correlated with the AT (r2 > 0.6, p < 0.001) in Delhi where as a moderate correlation (r2 > 0.6, p < 0.001) has been estimated for Maharashtra and Tamilnadu. Similarly, an intermediate range of correlation coefficient has been observed for other climatic parameters. A comparative study of climatic parameters in the current COVID-19 period with previous two years (2018-2019) has been carried out. Corresponding results imply a substantial trend for all three states. The range of climatic parameters have been found corresponding to maximum number of cases results as AT (25∼ 40 ° C), RH (40∼70%), AT (740∼965 mmHg), SR (200-250 W/mt 2) and WS (.5∼14 m/sec). Time series analysis depicts that the number of cases and mortality are increasing rapidly. COVID-19 epidemic peak has been predicted by SIR model for capital of India (New Delhi) and it would be around October 2020. The outcomes of this study will be helpful for the containment of COVID- 19 not only in India but globally.
Social Listening: A Thematic Analysis of COVID-19 Discussion on Social Media
Authors: Afolabi Sulaimon , Folorunso Sakinat Oluwabukonla , Bunyula Zinia Siphosethu , Banjo Oluwatobi Oluwaseyi , Matshika Sibusiso Sydney , Warrie Warrie Usenobong , Ngqambela Naledi , Adepoju Ayodeji Emmanuel , Rabophala Hendrica , Abimbola Olawale Victor , Olanipekun Michael Segun , Odukoya Adedayo Lateef
Published: July 2020

COVI-19 is a variant of coronavirus diseases that has destabilised the entire world and whose cure as at mid-2020 has become elusive. Social media is ablaze with discussions around the pandemic. There is the dire need to delineate the on-going conversations on the infection with the intention of creating awareness on people’s reaction, opinion, action and recommendation that are inimical to the wellbeing of the populace. Hence, this study is geared towards performing thematic analysis of the discussions on social media about COVID-19. We programmatically retrieved data from twitter between 1st March, 2020 to 30th June 2020 with covid-19 related keywords. We processed the data and later categorised them into themes that evolved from the tweets namely Herbs and Vegetables as COVID-10 Panacea, Self-Medication Due to Prescription by Non-Medical Practitioners on Social Media, Conspiracy Theories on COVID-19 and Fear and Anxiety Associated with COVID-19. The results show that many are resulting to herbs to protect themselves against the disease; taking drugs without doctor’s prescription; believing in conspiracy theories and having certain degree of fear.
Salt and Health: Public awareness, attitudes and practices in Sri Lanka to inform a behavior change communication campaign to reduce dietary salt
Authors: Jayatilleke Achala , Gunawardena Nalika , de Silva Angela , Wickramasinghe Champika , Gamlath Lakshman , Siriwardena Thilak , Kumarapeli Vindya , Vidanapathirana Janaki , Gunawardena Shanthi , Alagiyawanna AMAAP , Talagala Ishanka , Wickramasinghe Aravinda , Kumari Prabha , Ranatunga Prasad , Dhanapala Sapumal , Pendse Razia
Published: July 2020

Background

Sri Lankan citizens consume almost double the recommended daily amount of salt. Objective of this study was to assess the knowledge, attitudes and practices related to health effects of dietary salt among adults and adolescents in Sri Lanka to inform a national behavior change communication campaign.

Methods

We conducted a descriptive household survey among adults (n=1016) and adolescents (n=505) in 10 districts. An, interviewer administered questionnaire was used for data collection. The approximate amount of dietary salt intake of the individuals was estimated based on household purchases.

Findings

The recommended salt limit was identified by 40% of the population. Majority, adults (90.8%) and adolescents (86.1%) knew the adverse health effects of high salt intake. Although household monthly purchase of salt indicated consumption is much higher than recommended, 48.3% of adults and 45.9% of adolescents believed that they consume ‘just the right’ amount. Discretionary salt added to home cooking was a major contributor to intake, with approximately half (50%) adding salt when cooking rice, the staple. For health-related information most preferred (adults - 72%, adolescents – 69%) media is television.

Interpretation

The study identified gaps as well strengths in knowledge, attitudes and practices of Sri Lankans related to salt and health and recommends that the communication campaign include specific messaging to address gaps and leveraging on strengths. The survey identified adult females to be a key target group for the campaign and television is recommended as the mode of delivery.
Voxel-level Classification of Prostate Cancer Using a Four-Compartment Restriction Spectrum Imaging Model
Authors: Feng Christine H , Conlin Christopher C , Batra Kanha , Rodríguez-Soto Ana E , Karunamuni Roshan , Simon Aaron , Kuperman Joshua , Rakow-Penner Rebecca , Hahn Michael E , Dale Anders M , Seibert Tyler M
Published: July 2020

Purpose

Diffusion MRI is integral to detection of prostate cancer (PCa), but conventional ADC cannot capture the complexity of prostate tissues. A four-compartment restriction spectrum imaging (RSI4) model was recently found to optimally characterize pelvic diffusion signals, and the model coefficient for the slowest diffusion compartment, RSI4-C1, yielded greatest tumor conspicuity. In this study, RSI4-C1 was evaluated as a quantitative voxel-level classifier of PCa.

Methods

This was a retrospective analysis of 46 men who underwent an expanded-acquisition pelvic MRI for suspected PCa. Twenty-three men had no detectable cancer on biopsy or clinical follow-up; the other 23 had biopsy-proven PCa corresponding to a lesion on MRI (PI-RADS category 3-5). High-confidence cancer voxels were delineated by expert consensus, using imaging data and biopsy results. The entire prostate was considered benign in patients with no detectable cancer. Diffusion images were used to calculate RSI4-C1 and conventional ADC. Voxel-level discrimination of PCa from benign prostate tissue was assessed via receiver operating characteristic (ROC) curves generated by bootstrapping with patient-level case resampling. Specifically, we compared RSI4-C1 and conventional ADC on mean (and 95% CI) for two metrics: area under the curve (AUC) and false-positive rate for a sensitivity of 90% (FPR90). Classifier images were also compared.

Results

RSI4-C1 outperformed conventional ADC, with greater AUC [0.977 (0.951-0.991) vs. 0.921 (0.873-0.949)] and lower FPR90 [0.033 (0.009-0.083) vs. 0.201 (0.131-0.300)].

Conclusion

RSI4-C1 yielded a quantitative, voxel-level classifier of PCa that was superior to conventional ADC. RSI classifier images with a low false-positive rate might improve PCa detection.
Predicting the Emergence of SARS-CoV-2 Clades
Authors: Jain Siddharth , Xiao Xiongye , Bogdan Paul , Bruck Jehoshua
Published: July 2020

Evolution is a process of change where mutations in the viral RNA are selected based on their fitness for replication and survival. Given that current phylogenetic analysis of SARS-CoV-2 identifies new viral clades after they exhibit evolutionary selections, one wonders whether we can identify the viral selection and predict the emergence of new viral clades? Inspired by the Kolmogorov complexity concept, we propose a generative complexity (algorithmic) framework capable to analyze the viral RNA sequences by mapping the multiscale nucleotide dependencies onto a state machine, where states represent subsequences of nucleotides and state-transition probabilities encode the higher order interactions between these states. We apply computational learning and classification techniques to identify the active state-transitions and use those as features in clade classifiers to decipher the transient mutations (still evolving within a clade) and stable mutations (typical to a clade). As opposed to current analysis tools that rely on the edit distance between sequences and require sequence alignment, our method is computationally local, does not require sequence alignment and is robust to random errors (substitution, insertions and deletions). Relying on the GISAID viral sequence database, we demonstrate that our method can predict clade emergence, potentially aiding with the design of medications and vaccines.
An alternative binding mode of IGHV3-53 antibodies to the SARS-CoV-2 receptor binding domain
Authors: Wu Nicholas C. , Yuan Meng , Liu Hejun , Lee Chang-Chun D. , Zhu Xueyong , Bangaru Sandhya , Torres Jonathan L. , Caniels Tom G. , Brouwer Philip J.M. , van Gils Marit J. , Sanders Rogier W. , Ward Andrew B. , Wilson Ian A.
Published: July 2020

IGHV3-53-encoded neutralizing antibodies are commonly elicited during SARS-CoV-2 infection and target the receptor-binding domain (RBD) of the spike (S) protein. Such IGHV3-53 antibodies generally have a short CDR H3 due to structural constraints in binding the RBD (mode A). However, a small subset of IGHV3-53 antibodies to the RBD contain a longer CDR H3. Crystal structures of two IGHV3-53 neutralizing antibodies here demonstrate that a longer CDR H3 can be accommodated in a different binding mode (mode B). These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions. Overall, these findings emphasize the versatility of IGHV3-53 in this common antibody response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.
Hybrid optogenetic and electrical stimulation for greater spatial resolution and temporal fidelity of cochlear activation
Authors: Thompson Alex C. , Wise Andrew K. , Hart William L. , Needham Karina , Fallon James B. , Gunewardene Niliksha , Stoddart Paul R. , Richardson Rachael T.
Published: July 2020

Compared to electrical stimulation, optogenetic stimulation has the potential to improve the spatial precision of neural activation in neuroprostheses, but it requires intense light and has relatively poor temporal kinetics. We tested the effect of hybrid stimulation, which is the combination of subthreshold optical and electrical stimuli, on spectral and temporal fidelity in the cochlea by recording multiunit activity in the inferior colliculus of channelrhodopsin (H134R variant) transgenic mice. Pulsed light or biphasic electrical pulses were delivered to cochlear spiral ganglion neurons of acutely deafened mice, either as individual stimuli or as hybrid stimuli for which the timing of the electrical pulse had a varied delay relative to the start of the optical pulse. Facilitation occurred when subthreshold electrical stimuli were applied at the end of, or up to 3.75 ms after subthreshold optical pulses. The spread of activation resulting from hybrid stimulation was significantly narrower than electrical-only and optical-only stimulation (p<0.01), measured at equivalent suprathreshold levels of loudness that are relevant to cochlear implant users. Furthermore, temporal fidelity, measured as maximum following rates to 300 ms pulse trains bursts up to 240 Hz, was 2.4-fold greater than optical-only stimulation (p<0.05). By significantly improving spectral resolution of electrical- and optical-only stimulation and the temporal fidelity of optical-only stimulation, hybrid stimulation has the potential to increase the number of perceptually independent stimulating channels in a cochlear implant.
Antiviral effects of miRNAs in extracellular vesicles against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mutations in SARS-CoV-2 RNA virus
Authors: Park Jae Hyun , Choi Yuri , Lim Chul-Woo , Park Ji-Min , Yu Shin-Hye , Kim Yujin , Han Hae Jung , Kim Chun-Hyung , Song Young-Sook , Kim Chul , Moon Jisook
Published: July 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus 2019 (COVID-19). No treatment is available. Micro-RNAs (miRNAs) in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are potential novel therapeutic agents because of their ability to regulate gene expression by inhibiting mRNA. Thus, they may degrade the RNA genome of SARS-CoV-2. EVs can transfer miRNAs to recipient cells and regulate conditions within them. MSC-EVs harbor major therapeutic miRNAs that play important roles in the biological functions of virus-infected host cells. Here, we examined their potential impact on viral and immune responses. MSC-EVs contained 18 miRNAs predicted to interact directly with the 3’ UTR of SARS-CoV-2. These EVs suppressed SARS-CoV-2 replication in Vero E6 cells. In addition, five major miRNAs suppressed virus activity in a luciferase reporter assay by binding the 3’ UTR. MSC-EVs showed strong regenerative effects and potent anti-inflammatory activity which may prevent lethal cytokine storms. We confirmed that EVs regulated inflammatory responses by several cell types, including human brain cells that express the viral receptor ACE2, suggesting that the brain may be targeted by SARS-CoV-2. miRNAs in MSC-EVs have several advantages as therapeutic agents against SARS-CoV-2: 1) they bind specifically to the viral 3’ UTR, and are thus unlikely to have side effects; 2) because the 3’ UTR is highly conserved and rarely mutates, MSC-EV miRNAs could be used against novel variants arising during viral replication; and 3) unique cargoes carried by MSC-EVs can have diverse effects, such as regenerating damaged tissue and regulating immunity.
The landscape of micro-inversions provides clues for population genetic analysis of humans
Authors: Qu Li , Wang Luotong , He Feifei , Han Yilun , Yang Longshu , Wang May D. , Zhu Huaiqiu
Published: July 2020

Background

Variations in the human genome have been studied extensively. However, little is known about the role of micro-inversions (MIs), generally defined as small (<100 bp) inversions, in human evolution, diversity, and health. Depicting the pattern of MIs among diverse populations is critical for interpreting human evolutionary history and obtaining insight into genetic diseases.

Results

In this paper, we explored the distribution of MIs in genomes from 26 human populations and 7 nonhuman primate genomes and analyzed the phylogenetic structure of the 26 human populations based on the MIs. We further investigated the functions of the MIs located within genes associated with human health. With hg19 as the reference genome, we detected 6,968 MIs among the 1,937 human samples and 24,476 MIs among the 7 nonhuman primate genomes. The analyses of MIs in human genomes showed that the MIs were rarely located in exonic regions. Nonhuman primates and human populations shared only 82 inverted alleles, and Africans had the most inverted alleles in common with nonhuman primates, which was consistent with the “Out of Africa” hypothesis. The clustering of MIs among the human populations also coincided with human migration history and ancestral lineages.

Conclusions

We propose that MIs are potential evolutionary markers for investigating population dynamics. Our results revealed the diversity of MIs in human populations and showed that they are essential to constructing human population relationships and have a potential effect on human health.
Tracking mitochondrial density and positioning along a growing neuronal process in individualC. elegansneuron using a long-term growth and imaging microfluidic device
Authors: Mondal Sudip , Dubey Jyoti , Awasthi Anjali , Sure Guruprasad Reddy , Koushika Sandhya P.
Published: July 2020

The long cellular architecture of neurons requires regulation in part through transport and anchoring events to distribute intracellular organelles. During development, cellular and sub-cellular events such as organelle additions and their recruitment at specific sites on the growing axons occur over different time scales and often show inter-animal variability thus making it difficult to identify specific phenomena in population averages. To measure the variability in sub-cellular events such as organelle positions, we developed a microfluidic device to feed and immobilizeC. elegansfor high-resolution imaging over several days. The microfluidic device enabled long-term imaging of individual animals and allowed us to investigate organelle density using mitochondria as a testbed in a growing neuronal processin vivo. Sub-cellular imaging of an individual neuron in multiple animals, over 36 hours in our microfluidic device, shows the addition of new mitochondria along the neuronal process and an increase in the accumulation of synaptic vesicles at synapses, both organelles with important roles in neurons. Long-term imaging of individualC. eleganstouch receptor neurons identifies addition of new mitochondria and interacts with other moving mitochondria only through fission and fusion events. The addition of new mitochondria takes place along the entire neuronal process length and the threshold for the addition of a new mitochondrion is when the average separation between the two pre-existing mitochondria exceeds 24 micrometers.
NBS1-CtIP–Mediated DNA End Resection Regulates cGAS Binding to Micronuclei
Authors: Abdisalaam Salim , Mukherjee Shibani , Bhattacharya Souparno , Sinha Debapriya , Kumari Sharda , Sadek Hesham A. , Ortega Janice , Li Guo-Min , Asaithamby Aroumougame
Published: July 2020

Cyclic GMP-AMP synthase (cGAS), an important component of immune signaling, is hyperactivated in cells defective for DNA damage response (DDR) signaling. However, a direct role for DDR factors in the regulation of cGAS functions is mostly unknown. Here, we provide novel evidence that Nijmegen breakage syndrome 1 (NBS1) protein, a well-studied DNA double-strand break (DSB) sensor, in coordination with ATM, a protein kinase, and CtBP-interacting protein (CtIP), a DNA end resection factor, functions as an upstream regulator of cGAS binding to micronuclei. Upon NBS1 binding to micronuclei via its fork-head–associated domain, it recruits ATM and CtIP via its N- and C-terminal domains, respectively. Subsequently, ATM stabilizes NBS1’s interaction with micronuclei, and CtIP converts DSB ends into single-strand DNA ends, and these two key events preclude cGAS from binding to micronuclei. Notably, we show that purified cGAS cannot form a complex with DNA substrates that mimic resected DNA ends in vitro. Thus, NBS1 together with its binding partners modify the chromatin architecture of the micronuclei and that plays a critical role in cGAS’s binding to micronuclei.
A Conserved TCRβ signature dominates a highly polyclonal T-cell expansion during the acute phase of a murine malaria infection
Authors: Smith Natasha L. , Nahrendorf Wiebke , Sutherland Catherine , Mooney Jason P. , Thompson Joanne , Spence Philip J. , Cowan Graeme J. M.
Published: July 2020

CD4+αβ T-cells are key mediators of the immune response to a firstPlasmodiuminfection, undergoing extensive activation and splenic expansion during the acute phase of an infection. However, the clonality and clonal composition of this expansion has not previously been described. Using a comparative infection model, we sequenced the splenic CD4+T-cell receptor repertoires generated over the time-course of aPlasmodium chabaudiinfection. We show through repeat replicate experiments, single-cell RNA-seq, and analyses of independent RNA-seq data, that following a first infection – within a highly polyclonal expansion – T-effector repertoires are consistently dominated by TRBV3 gene usage. Clustering by sequence similarity, we find the same dominant clonal signature is expanded across replicates in the acute phase of an infection, revealing a conserved pathogen-specific T-cell response that is consistently a hallmark of a first infection, but not expanded upon re-challenge. Determining the host or parasite factors driving this conserved response may uncover novel immune targets for malaria therapeutic purposes.
Transcription factor binding process is the primary driver of noise in gene expression
Authors: Parab Lavisha , Pal Sampriti , Dhar Riddhiman
Published: July 2020

Noise in expression of individual genes gives rise to variations in activity of cellular pathways and generates heterogeneity in cellular phenotypes. Phenotypic heterogeneity has important implications for antibiotic persistence, mutation penetrance, cancer growth and therapy resistance. Specific molecular features such as presence of the TATA box sequence and promoter nucleosome occupancy have been associated with noise. However, the relative importance of these features in noise regulation has not yet been assessed. In addition, how well these features can predict noise also remains unclear. Here through an integrated statistical model of gene expression noise in yeast we found that the number of regulating transcription factors (TFs) was a key predictor of noise. With an increase in the number of regulatory TFs, we observed a rise in the number of TFs that bound cooperatively. In addition, increased number of TFs meant more overlaps in TF binding sites that caused competition between TFs for binding to the same region of the promoter. Through modeling of TF binding to promoter and applying stochastic simulations, we demonstrated that competition and cooperation among TFs could increase noise. Thus, our work uncovers a process of noise regulation that arises out of the dynamics of gene regulation and is not dependent on any specific transcription factor or specific promoter sequence.
Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys
Authors: Khani Mohammadreza , Fu Audrey Q. , Pluid Joshua , Gibbs Christina P. , Oshinski John N. , Xing Tao , Stewart Gregory R. , Zeller Jillynne R. , Martin Bryn A.
Published: July 2020

A detailed understanding of the CSF dynamics is essential for testing and evaluation of intrathecal drug delivery. Preclinical work using large-animal models (e.g., monkeys, dogs and sheep) has great utility for defining spinal drug distribution/pharmacokinetics and provide an important tool for defining safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there is a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with the cervical implantation. CSF flow rate decreased up to 54.7% when the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation
Antifungal effects of PC945, a novel inhaled triazole, onCandida albicans-infected immunocompromised mice
Authors: Nishimoto Yuki , Ito Kazuhiro , Kimura Genki , Lucas Kirstie A. , Daly Leah , Strong Pete , Kizawa Yasuo
Published: July 2020

AlthoughCandida spp.are frequently detected in fungal cultures of respiratory secretions, their presence is normally assumed to reflect benign colonization. However, there is growing evidence thatCandida spp.are involved in the pathogenesis of respiratory diseases such as bronchiectasis and asthma. The aim of this study is to investigate thein vitroandin vivoeffects of a novel antifungal triazole, PC945, optimised for topical delivery, againstC. albicans. In temporarily neutropenic, immunocompromised mice,C. albicans(529L [ATCC®MYA4901™] strain), inoculated intranasally, induced acute lung injury and death, associated with higher fungal burden and cytokine induction in the lung. PC945 saline suspension, dosed intranasally once daily, starting one day post candida inoculation, dose-dependently (0.56 ~ 14 μg/mouse) improved survival rate and inhibited fungal load in the lung on Day 5 post inoculation. These effects by PC945 were 7 ~ 25-fold more potent than those of voriconazole, despite being of similarin vitroantifungal activity versus this strain. Furthermore, extended prophylaxis with low dose PC945 (0.56 μg/mouse) was found to inhibit fungal load more potently than the shorter treatment regimens, suggesting antifungal effects of PC945 accumulated on repeat dosing. In addition, antifungal susceptibility testing on 88 candida isolates(C. albicans, C. parapsilosis, C. tropicalis, C. lucitaniae, C. glabrata, C. guilliermondii)revealed that PC945 has potent effects onCandidaspecies broadly. Thus, PC945 has the potential to be a novel topical therapy for the treatment ofC. albicanspulmonary infection in humans.
Modal properties of fruit-rachilla system of the macaw palm
Authors: de Melo Villar Flora Maria , de Assis de Carvalho Pinto Francisco , Santos Fabio Lucio , de Queiroz Daniel Marçal , Pereira Mariana Ribeiro , Magalhães Valente Domingos Sárvio
Published: July 2020

The macaw palm has been domesticated due to its potential use in the production of biodiesel. One of the current challenges in this area is to determine the proper information and develop the technologies required for using macaw palm, allowing it to contribute to the sustainable production of feedstock for biodiesel industry. The principle of mechanical vibration can be employed for the detachment of fruits from a tree bunch, and it is therefore necessary to study the dynamic behavior of the macaw palm fruit-rachilla system during the vibration. Hence, the modal properties of the system were determined. A study on the dynamic behaviors was carried out using a deterministic finite element model, and the natural frequencies were obtained through a frequency-scanning test to evaluate the model. The mean relative error (MRE) between the measured and simulated natural frequencies was also used to evaluate the model. The natural frequencies, determined experimentally, varied between 26.21 and 33.45 Hz on average, whereas the simulated frequencies varied from 24.81 to 39.27 Hz. The overall MRE was 9.08%. Once the model was validated, a sensibility test showed that the density of fruit and the elasticity modulus are the parameters that most influence the natural frequencies of the fruit-rachilla system.
Cargo modulates the conformation of the nuclear pore in living cells
Authors: Pulupa Joan , Prior Harriet , Johnson Daniel S. , Simon Sanford M.
Published: July 2020

While the static structure of the nuclear pore complex (NPC) continues to be refined with cryo-EM and x-ray crystallography, thein vivoconformational dynamics of the NPC remain under-explored. We developed sensors that report on the orientation of NPC components by rigidly conjugating mEGFP to different NPC proteins. Our studies show conformational changes to select domains of Nups within the inner ring (Nup54, Nup58, Nup62) when transport through the NPC is perturbed and no conformational changes to Nups elsewhere in the NPC. Our results suggest that select components of the NPC are flexible and undergo conformational changes upon engaging with cargo.
Flagellar structures from the bacteriumCaulobacter crescentusand implications for phage ϕCbK predation of multi-flagellin bacteria
Authors: Montemayor Eric J. , Ploscariu Nicoleta T. , Sanchez Juan C. , Parrell Daniel , Dillard Rebecca S. , Shebelut Conrad W. , Ke Zunlong , Guerrero-Ferreira Ricardo C. , Wright Elizabeth R.
Published: July 2020

Caulobacter crescentusis a gram-negative alpha-proteobacterium that commonly lives in oligotrophic fresh and salt-water environments.C. crescentusis a host to many bacteriophages, including ϕCbK and ϕCbK-like bacteriophages, which first adsorb to cells by interaction with the bacterial flagellum. It is commonly thought that the six paralogs of the flagellin gene present inC. crescentusare important for bacteriophage evasion. Here, we show that deletion of specific flagellins inC. crescentuscan indeed attenuate ϕCbK adsorption efficiency, although no single deletion completely ablates ϕCbK adsorption. Thus, bacteriophage ϕCbK likely recognizes a common motif amongst the six known flagellins inC. crescentuswith varying degrees of efficiency. Interestingly, we observe that most deletion strains still generate flagellar filaments, with the exception of a strain that contains only the most divergent flagellin, FljJ, or a strain that contains only FljN and FljO. To visualize the surface residues that are likely recognized by ϕCbK, we determined two high-resolution structures of the FljK filament, with and without an amino acid substitution that induces straightening of the filament. We observe post-translational modifications on conserved surface threonine residues of FljK that are likely O-linked glycans. The possibility of interplay between these modifications and ϕCbK adsorption is discussed. We also determined the structure of a filament composed of a heterogeneous mixture of FljK and FljL, the final resolution of which was limited to approximately 4.6 Å. Altogether, this work builds a platform for future investigation of how phage ϕCbK infectsC. crescentusat the molecular level.