bluuebunny/crossref_metadata_2025 huggingface dataset:
Buried treasure—marine turtles do not ‘disguise’ or ‘camouflage’ their nests but avoid them and create a decoy trail
Authors: Burns Thomas J. , Thomson Rory R. , McLaren Rosemary A. , Rawlinson Jack , McMillan Euan , Davidson Hannah , Kennedy Malcolm W.
Published: May 2020

After laying their eggs and refilling the egg chamber, sea turtles scatter sand extensively around the nest site. This is presumed to camouflage the nest, or optimize local conditions for egg development, but a consensus on its function is lacking. We quantified activity and mapped the movements of hawksbill (
Eretmochelys imbricata
) and leatherback (
Dermochelys coriacea
) turtles during sand-scattering. For leatherbacks, we also recorded activity at each sand-scattering position. For hawksbills, we recorded breathing rates during nesting as an indicator of metabolic investment and compared with published values for leatherbacks. Temporal and inferred metabolic investment in sand-scattering was substantial for both species. Neither species remained near the nest while sand-scattering, instead moving to several other positions to scatter sand, changing direction each time, progressively displacing themselves from the nest site. Movement patterns were highly diverse between individuals, but activity at each sand-scattering position changed little between completion of egg chamber refilling and return to the sea. Our findings are inconsistent with sand-scattering being to directly camouflage the nest, or primarily for modifying the nest-proximal environment. Instead, they are consistent with the construction of a series of dispersed decoy nests that may reduce the discovery of nests by predators.
Characterization of SARS-CoV-2 viral diversity within and across hosts
Authors: Sashittal Palash , Luo Yunan , Peng Jian , El-Kebir Mohammed
Published: May 2020

In light of the current COVID-19 pandemic, there is an urgent need to accurately infer the evolutionary and transmission history of the virus to inform real-time outbreak management, public health policies and mitigation strategies. Current phylogenetic and phylodynamic approaches typically use consensus sequences, essentially assuming the presence of a single viral strain per host. Here, we analyze 621 bulk RNA sequencing samples and 7,540 consensus sequences from COVID-19 patients, and identify multiple strains of the virus, SARS-CoV-2, in four major clades that are prevalent within and across hosts. In particular, we find evidence for (i) within-host diversity across phylogenetic clades, (ii) putative cases of recombination, multi-strain and/or superinfections as well as (iii) distinct strain profiles across geographical locations and time. Our findings and algorithms will facilitate more detailed evolutionary analyses and contact tracing that specifically account for within-host viral diversity in the ongoing COVID-19 pandemic as well as future pandemics.
Beneficial effect of corticosteroids in severe COVID-19 pneumonia: a propensity score matching analysis
Authors: Chroboczek Tomasz , Lacoste Marie , Wackenheim Chloe , Challan-Belval Thibaut , Amar Benjamin , Boisson Thomas , Hubac Jason , Leduc Dominique , Masse Colleen , Dechaene Victor , Touhiri-Maximin Laetitia , Megessier Sandrine , Lassale Camille
Published: May 2020

Background

Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for Coronavirus Disease 2019 (COVID-19), is spreading worldwide, causing significant morbidity and mortality. No specific treatment has yet clearly shown to improve the disease’s evolution. Validated therapeutic options are urgently needed.

Methods

In this retrospective study, we aimed to evaluate determinants of the prognosis of the disease in 70 patients with COVID-19 severe pneumonia (i.e. requiring at least 3 liters of oxygen) hospitalized between 10 March and 9 April, 2020, in the Centre Hospitalier Alpes Léman, France. The main outcome was oro-tracheal intubation and the exposure of interest was corticotherapy. Since this was not a randomized trial, we used propensity score matching to estimate average treatment effect.

Results

There was evidence that corticotherapy lowered the risk of intubation with a risk difference of −47.1% (95% confidence interval −71.8% to −22.5%).

Conclusion

Corticosteroid, a well-known, easily available, and cheap treatment, could be an important tool in management of severe COVID-19 patients with respiratory failure. Not only could it provide an individual benefit, but also, in the setting of the COVID-19 ongoing pandemic, lower the burden on our vulnerable healthcare systems.

Key points

By propensity score matching analysis, the average treatment effect of corticosteroids on 70 patients with severe COVID-19 pneumonia was estimated. Corticosteroid therapy lowered the risk of intubation with a risk difference of −47.1% (95% confidence interval −71.8% to −22.5%).
Mathematical model of COVID-19 spread in Turkey and South Africa: Theory, methods and applications
Authors: Atangana Abdon , İğret Araz Seda
Published: May 2020

A comprehensive study about the spread of COVID-19 cases in Turkey and South Africa has been presented in this paper. An exhaustive statistical analysis encompassing arithmetic, geometric, harmonic means, standard deviation, skewness, variance, Pearson and Spearman correlation was derived from the data collected from Turkey and South Africa within the period of 11 March 2020 to 3 May 2020 and 05 March and 3 of May respectively. It was observed that in the case of Turkey, a negative Spearman correlation for the number of infected class and a positive Spearman correlation for both the number of deaths and recoveries were obtained. This implied that the daily infections could decrease, while the daily deaths and number of recovered people could increase under current conditions. In the case of South Africa, a negative Spearman correlation for both daily deaths and daily infected people was obtained, indicating that these numbers may decrease if the current conditions are maintained. The utilization of a statistical technique predicted the daily number of infected, recovered and dead people for each country; and three results were obtained for Turkey, namely an upper boundary, a prediction from current situation and lower boundary. The prediction shows that Turkey may register in the near future approximately more than 6000 new infections in a day as worst case scenario; and less than 300 cases in the perfect scenario. However, the country could register in the near future a daily number of 27000 people recovered from COVID-19 in the perfect scenario; and less than 5000 people in a worst scenario. Moreover, Turkey in a worst-case scenario could record a high number of approximately 200 deaths per day; and less than 150 deaths in a perfect scenario. Similarly, in the case of South Africa, the prediction results show that in the near future the country could register about 500 new infected cases daily and more than 25 deaths in the worst scenario; while in a perfect scenario less than 50 new infected and zero death cases could be recorded. The histograms of the daily number of newly infected, recovered and death showed a sign of lognormal and normal distribution, which is presented using the Bell curving method parameters estimation. A new mathematical model COVID-19 comprised of nine classes was suggested; of which a formula of the reproductive number, well-poseness of the solutions and the stability analysis were presented in details. The suggested model was further extended to the scope of nonlocal operators for each case; whereby the Atangana-Seda numerical method was used to provide numerical solutions, and simulations were performed for different non-integer numbers. Additionally, sections devoted to control optimal and others dedicated to compare cases between Turkey and South Africa with the aim to comprehend why there are less numbers of deaths and infected people in South Africa than Turkey were presented in details.
Characterizing the Clinical and Genetic Spectrum of Polycystic Ovary Syndrome in Electronic Health Records
Authors: Actkins Ky'Era V. , Singh Kritika , Hucks Donald , Velez Edwards Digna R. , Aldrich Melinda , Cha Jeeyeon , Wellons Melissa , Davis Lea K.
Published: May 2020

Context: Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility, yet current diagnostic criteria are ineffective at identifying patients whose symptoms reside outside strict diagnostic criteria. As a result, PCOS is under diagnosed and its etiology is poorly understood.

Objective: We aim to characterize the phenotypic spectrum of PCOS clinical features within and across racial and ethnic groups.

Methods: We developed a strictly defined PCOS algorithm (PCOSregex-strict) using International Classification of Diseases, 9th and 10th edition (ICD9/10) and regular expressions mined from clinical notes in electronic health records (EHRs) data. We then systematically relaxed the inclusion criteria to evaluate the change in epidemiological and genetic associations resulting in three subsequent algorithms (PCOScoded-broad, PCOScoded-strict, PCOSregex-broad). We evaluated the performance of each phenotyping approach and characterized prominent clinical features observed in racially and ethnically diverse PCOS patients.

Results: The best performing algorithm was our PCOScoded-strict algorithm with a positive predictive value (PPV) of 98%. Individuals classified as cases by this algorithm had significantly higher body mass index (BMI), insulin levels, free testosterone values, and genetic risk scores for PCOS, compared to controls. Median BMI was higher in African American women with PCOS compared to White and Hispanic women with PCOS.

Conclusions: PCOS symptoms are observed across a severity spectrum that parallels genetic burden. Racial and ethnic group differences exist in PCOS symptomology and metabolic health across different phenotyping strategies.
Epidemiological, socio-demographic and clinical features of the early phase of the COVID-19 epidemic in Ecuador
Authors: Ortiz-Prado Esteban , Simbaña-Rivera Katherine , Diaz Ana Maria , Barreto Alejandra , Moyano Carla , Arcos Vannesa , Vásconez-González Eduardo , Paz Clara , Simbaña-Guaycha Fernanda , Molestina-Luzuriaga Martin , Fernández-Naranjo Raúl , Feijoo Javier , Henriquez Aquiles R. , Adana Lila , López Cortés Andrés , Fletcher Isabel , Lowe Rachel , Gómez-Barreno Lenin
Published: May 2020

Background

The SARS-CoV-2 virus has spread rapidly around the globe. Nevertheless, there is limited information describing the characteristics and outcomes of COVID-19 patients in Latin America.

Methods

We conducted a cross-sectional analysis of 9,468 confirmed COVID-19 cases reported in Ecuador. We calculated overall incidence, mortality, case fatality rates, disability adjusted life years, attack and crude mortality rates, as well as relative risk and relative odds of death, adjusted for age, sex and presence of comorbidities.

Results

A total of 9,468 positive COVID-19 cases and 474 deaths were included in the analysis. Men accounted for 55.4% (n = 5, 247) of cases and women for 44.6% (n = 4, 221). We found the presence of comorbidities, being male and older than 65 years were important determinants of mortality. Coastal regions were most affected by COVID-19, with higher mortality rates than the highlands. Fatigue was reported in 53.2% of the patients, followed by headache (43%), dry cough (41.7%), ageusia (37.1%) and anosmia (36.1%).

Conclusion

We present the first analysis of the burden of COVID-19 in Ecuador. Our findings show that men are at higher risk of dying from COVID-19 than women, and risk increases with age and the presence of comorbidities. We also found that blue-collar workers and the unemployed are at greater risk of dying. These early observations offer clinical insights for the medical community to help improve patient care and for public health officials to strengthen Ecuador’s response to the outbreak.
Rapid response flow cytometric assay for the detection of antibody responses to SARS-CoV-2
Authors: Lapuente Dennis , Maier Clara , Irrgang Pascal , Huebner Julian , Peter Sophia Antonia , Hoffmann Markus , Ensser Armin , Ziegler Katharina , Winkler Thomas H. , Birkholz Thorsten , Kremer Andreas E. , Steininger Philipp , Korn Klaus , Neipel Frank , Ueberla Klaus , Tenbusch Matthias
Published: May 2020

SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing a serious pandemic. While reliable nucleic acid-based diagnostic assays were rapidly available, there exists only a limited number of validated serological assays. Here, we evaluated a novel flow cytometric approach based on antigen-expressing HEK 293T cells to assess spike-specific IgG and IgM antibody responses. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA systems, while also revealing the highest sensitivity in specimens from PCR-confirmed SARS-CoV-2 infected patients. Additionally, a soluble Angiotensin-Converting-Enzyme 2 (ACE-2) variant was established as external standard to quantify spike-specific antibody responses on different assay platforms. In conclusion, our newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies, which can be easily adopted in different laboratories and does not rely on external supply of assay kits.
Stereotactic arrhythmia radioablation (STAR) in patients with ventricular tachycardia: a meta-analysis of efficacy and safety outcomes.
Authors: Viani GUSTAVO Arruda , Pavoni Juliana Fernandes , de Fendi Ligia Issa
Published: May 2020

Objectives: The effectiveness and safety of STAR in patients with refractory ventricular tachycardia (VT) to catheter ablation are limited to small series. We performed a meta-analysis of observational studies to summarize existing data about efficacy and toxicity following START for VT. Methods: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through March 2020. We followed the PRISMA and MOOSE guidelines. An estimative of % VT burden reduction at 6 months higher than 85% was considered effective. A rate of any grade 3 or higher toxicity lower than 10% and no grade 4 or 5 were considered safe. Results: Four observational studies with a total of 39 patients treated were included. The % of VT burden reduction at 6 months was 91% (CI95% from 83 to 100%). The consumption of lower than 2 anti-arrhythmia drugs (AAD) at 6 months was 81%. The ejection fraction improved in 12.8%, unchanged 82%, and decreased by 5.2%. The overall survival (OS) was 92% and 82 % in 6 and 12 months. The cardiac death and disease-specific survival at 12 months were 12% and 88.5%. Late grade 3 toxicity 5% with no grade 4-5. Conclusion: STAR produced satisfactory % of VT burden reduction, with a significant reduction in the consumption of AAD at 6 months, and no severe toxicity. These findings support the continued work to develop new trials and to adopt STAR as a treatment option for medical practice.
Three pictures of COVID-19 behavior in Italy: similar growth and different degrowth
Authors: Feoli A. , Iannella A. L. , Benedetto E.
Published: May 2020

In this short note, we present an analysis of the data regarding Coronavirus (COVID-19) in Italy. We have used the official database provided by the Italian Civil Protection. Since the total number of people infected by the virus is uncertain, we have considered the trend of ICU patients, ICU patients plus deaths, and finally the sum of hospitalized patients plus the deceased. The growth of the corresponding curves is similar for all the three graphs while the trend after the turning point is completely different. We find that the curve of ICU patients can be a useful tool to monitor the behavior of epidemic and a model to predict the future evolution of COVID-19.
Marginal Bone Loss and Aesthetics Around Zirconia and Titanium Dental Implants-A Metanalysis
Authors: Sathwika Pulijala , Chandra Rampalli Viswa
Published: May 2020

AIM: To evaluate and compare the marginal bone loss and aesthetic outcomes of zirconia implants with titanium implants in randomized controlled trials (RCTs).
MATERIAL AND METHODS: Electronic [PubMed] and hand searches were performed to identify randomized controlled trials that were published between January 2008 to April 2020 which investigated and compared various outcomes between zirconia and titanium dental implants. Outcomes included assessment of marginal bone loss and aesthetics using spectrophotometric measurements. Meta-analysis was performed to estimate the above parameters among various studies.
RESULTS: A total of 58 articles were screened for titles and abstracts. Subsequently 8 articles were selected for data extraction and evaluation. Zirconia implants were investigated and compared to titanium implants for marginal bone loss [MBL]. Customized zirconia and titanium abutments seated over implants were analyzed for aesthetic outcomes using spectrophotometric method using CIE-Lab measurements. Meta-analysis estimated that zirconia implants exhibited marginal bone loss reduction of 0.179mm (95% CI, 0.02 to 0.33) and -0.242mm (95% CI, -4.026 to 3.542) in aesthetic measurements than titanium implants.
CONCLUSIONS: No heterogeneity was observed among studies analyzed for marginal bone loss and significant differences were noticed between two groups. Noticeable heterogeneity was observed among studies assessing aesthetics using spectrophotometry and CIE-Lab measurements and results revealed no many significant differences between the two groups.
Effects of mobility and multi-seeding on the propagation of the COVID-19 in Spain
Authors: Mazzoli Mattia , Mateo David , Hernando Alberto , Meloni Sandro , Ramasco José J.
Published: May 2020

Assessing the impact of mobility on epidemic spreading is of crucial importance for understanding the effect of policies like mass quarantines and selective re-openings. High mobility between areas contribute to the importation of cases, affecting the spread of the disease. While many factors influence local incidence and making it more or less homogeneous with respect to other areas, the importance of multi-seeding has often been overlooked. Multi-seeding occurs when several independent (non-clustered) infected individuals arrive at a susceptible population. This can give rise to autonomous outbreaks that impact separate areas of the contact (social) network. Such mechanism has the potential to boost local incidence and size, making control and tracing measures less effective. In Spain, the high heterogeneity in incidence between similar areas despite the uniform mobility control measures taken suggests that multi-seeding could have played an important role in shaping the spreading of the disease. In this work, we focus on the spreading of SARS-CoV-2 among the 52 Spanish provinces, showing that local peaks of incidence and mortality strongly correlate with mobility occurred in the early-stage weeks from and to Madrid, the main mobility hub and where the initial local outbreak unfolded. These results clarify the higher order effects that mobility can have on the evolution of an epidemic and highlight the relevance of its control.
The Early Food Insecurity Impacts of COVID-19
Authors: Niles Meredith T. , Bertmann Farryl , Belarmino Emily H. , Wentworth Thomas , Biehl Erin , Neff Roni A.
Published: May 2020

Background
COVID-19 has disrupted food access and impacted food insecurity, which is associated with numerous adverse individual and public health outcomes.

Methods
We conducted a statewide population-level survey in Vermont from March 29-April 12, 2020, during the beginning of a statewide stay-at-home order. We utilized the USDA six-item validated food security module to measure food insecurity before COVID-19 and since COVID-19. We assessed food insecurity prevalence and reported food access challenges, coping strategies, and perceived helpful interventions among food secure, consistently food insecure (pre-and post COVID-19), and newly food insecure (post COVID-19) respondents.

Results
Among 3,219 respondents, there was a 33% increase in household food insecurity since COVID-19 (p<0.001), with 35.6% of food insecure households classified as newly food insecure. Respondents experiencing a job loss were more likely to experience food insecurity (OR 3.43; 95% CI, 2.45-4.80). Multiple physical and economic barriers, as well as concerns related to food access during COVID-19, are reported, with respondents experiencing household food insecurity more likely to face access challenges (p<0.001). Significant differences in coping strategies were documented between respondents in newly food insecure vs. consistently insecure households.

Conclusions
Since the declaration of the COVID-19 pandemic, there has been a significant increase in food insecurity in Vermont, accompanied by major food access barriers. These findings have important potential impacts on individual health, including mental health and malnutrition, as well as on future healthcare costs. We suggest proactive strategies to address food insecurity during this crisis.
Model-based Cellular Kinetic Analysis of Chimeric Antigen Receptor-T Cells in Humans
Authors: Liu Can , Ayyar Vivaswath S. , Zheng Xirong , Chen Wenbo , Zheng Songmao , Mody Hardik , Wang Weirong , Heald Donald , Singh Aman P. , Cao Yanguang
Published: May 2020

Chimeric antigen receptor (CAR)-T cell therapy has achieved considerable success in treating B-cell hematologic malignancies. However, the challenges of extending CAR-T therapy to other tumor types, particularly solid tumors, remain appreciable. There are substantial variabilities in CAR-T cellular kinetics across CAR-designs, CAR-T products, dosing regimens, patient responses, disease types, tumor burdens, and lymphodepletion conditions. As a “living drug”, CAR-T cellular kinetics typically exhibit four distinct phases: distribution, expansion, contraction, and persistence. The cellular kinetics of CAR-T may correlate with patient responses, but which factors determine CAR-T cellular kinetics remain poorly defined. Herein, we developed a cellular kinetic model to retrospectively characterize CAR-T kinetics in 217 patients from 7 trials and compared CAR-T kinetics across response status, patient populations, and tumor types. Based on our analysis results, CAR-T cells exhibited a significantly higher cell proliferation rate and capacity but a lower contraction rate in patients who responded to treatment. CAR-T cells proliferate to a higher degree in hematologic malignancies than in solid tumors. Within the assessed dose ranges (107–109 cells), CAR-T doses were weakly correlated with CAR-T cellular kinetics and patient response status. In conclusion, the developed CAR-T cellular kinetic model adequately characterized the multiphasic CAR-T cellular kinetics and supported systematic evaluations of the potential influencing factors, which can have significant implications for the development of more effective CAR-T therapies.
Monitoring the propagation of COVID-19-pandemic first waves
Authors: Knafo William
Published: May 2020

A phenomenological approach is proposed to monitor the propagation of the COVID-19-pandemic first waves. A large set of data collected at a worldwide scale during the first months of 2020 is compiled into series of semi-logarithmic plots, for a selection of thirty-two countries from the five continents. Three regimes are identified in the propagation of an epidemic wave: a pre-epidemic regime 1, an exponential-growth regime 2, and a resorption regime 3. A two-parameters scaling of the first-wave death variation reported in China is used to fit those reported in other countries. Comparison is made between the propagation of the pandemic in different countries, which are classified in four groups, from group A where the pandemic first waves were contained efficiently, to group D where the pandemic first waves widely spread. Group A is mainly composed of Asian countries, where fast and efficient measures have been applied. Group D is composed of Western-Europe countries and the United States of America, where late decisions and confused political communication (pandemic seriousness, protection masks, herd immunity etc.) led to significant death tolls. The threat of large resurging epidemic waves after a hasty lockdown lift is discussed, in particular for the countries from group D, where the number of contagious people remained high in the beginning of May 2020. The situation is opposite in Asian countries from group A, where the number of contagious people was successfully maintained to a low level. In particular, the results obtained by Hong Kong and South Korea are highlighted, and the measures taken there are presented as virtuous examples that other countries may follow.
Brief sensory deprivation triggers cell type-specific structural and functional plasticity in olfactory bulb neurons
Authors: Galliano Elisa , Hahn Christiane , Browne Lorcan , Villamayor Paula R. , Grubb Matthew S.
Published: May 2020

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odour processing. We induced experience-dependent plasticity in mice by blocking one nostril for a day, a minimally-invasive manipulation which leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory deprivation produced structural and functional plasticity in one highly specialised bulbar cell type: axon-bearing dopaminergic neurons in the glomerular layer. After 24h naris occlusion, the axon initial segment (AIS) in bulbar dopaminergic neurons became significantly shorter, a structural modification that was also associated with a decrease in intrinsic excitability. These effects were specific to the AIS-positive dopaminergic subpopulation, because no experience-dependent alterations in intrinsic excitability were observed in AIS-negative dopaminergic cells. Moreover, 24h naris occlusion produced no structural changes at the AIS of bulbar excitatory neurons – mitral/tufted and external tufted cells – nor did it alter their intrinsic excitability. By targeting excitability in one specialised dopaminergic subpopulation, experience-dependent plasticity in early olfactory networks might act to fine-tune sensory processing in the face of continually fluctuating inputs.
PhotoModPlus: A webserver for photosynthetic protein prediction from a genome neighborhood feature
Authors: Sangphukieo Apiwat , Laomettachit Teeraphan , Ruengjitchatchawalya Marasri
Published: May 2020

Identification of photosynthetic proteins and their functions is essential for understanding and improving photosynthetic efficiency. We present here a new webserver called PhotoModPlus as a platform to predict photosynthetic proteins via genome neighborhood networks (GNN) and a machine learning method. GNN facilitates users to visualize the overview of the conserved neighboring genes from multiple photosynthetic prokaryotic genomes and provides functional guidance to the query input. We also integrated a newly developed machine learning model for predicting photosynthesis-specific functions based on 24 prokaryotic photosynthesis-related GO terms, namely PhotoModGO, into the webserver. The new model was developed using a multi-label classification approach and genome neighborhood features. The performance of the new model was up to 0.872 of F1 measure, which was better than the sequence-based approaches evaluated by nested five-fold cross-validation. Finally, we demonstrated the applications of the webserver and the new model in the identification of novel photosynthetic proteins. The server was user-friendly designed and compatible with all devices and available athttp://bicep.kmutt.ac.th/photomodorhttp://bicep2.kmutt.ac.th/photomod.
Acute effects of prolactin on hypothalamic prolactin receptor expressing neurones in the mouse
Authors: Georgescu T. , Ladyman S.R. , Brown R.S.E. , Grattan D.R.
Published: May 2020

The anterior pituitary hormone, prolactin, is a fundamental regulator of lactation, and also plays a role in many other physiological processes including maternal behaviour, reproduction, immune response and even energy balance. Indeed, prolactin receptors (Prlr) are widely distributed throughout the body, including a number of different brain regions, further attesting to its pleiotropic nature. Within the brain, previous research has identified key areas upon which prolactin exerts effects on gene transcription through the canonical JAK2/STAT5 pathway downstream of the Prlr. In some neurones, however, such as the tuberoinfundibular dopamine neurones that control prolactin secretion, prolactin can also exert rapid actions to stimulate neuronal activity. While prolactin-induced activation of STAT5 has been described in a wide variety of brain regions, its capacity for acute modulation of electrical properties of many Prlr-expressing neurones remains to be elucidated. To investigate how widespread these rapid actions of prolactin are in various Prlr-expressing neurones, we utilised a transgenic mouse line in which Cre recombinase is specifically expressed in the coding region of the prolactin long form receptor gene (Prlr-iCre). This mouse line was crossed with a Cre-dependent calcium indicator (GCaMP6f) transgenic mouse, allowing us to visually monitor the electrical activity of Prlr-expressing neurones inex vivo200μm brain slice preparations. Here, we survey hypothalamic regions implicated in prolactin’s diverse physiological functions such as: the arcuate (ARC) and paraventricular nuclei of the hypothalamus (PVN), and the medial preoptic area (MPOA). We observe that in both males and virgin and lactating females, bath application of prolactin is able to induce electrical changes in a subset of Prlr-expressing cells in all of these brain regions. The effects we detected ranged from rapid or sustained increases in intracellular calcium to inhibitory effects, indicating a heterogeneous nature of these Prlr-expressing populations. These results enhance our understanding of mechanisms by which prolactin acts on hypothalamic neurones and provide insights into how prolactin might influence neuronal circuits in the mouse brain.
Reduced purine biosynthesis in humans after their divergence from Neandertals
Authors: Stepanova Vita , Moczulska Kaja Ewa , Vacano Guido N. , Ju Xiang-chun , Riesenberg Stephan , Macak Dominik , Maricic Tomislav , Dombrowski Linda , Schörnig Maria , Anastassiadis Konstantinos , Baker Oliver , Naumann Ronald , Khrameeva Ekaterina , Vanushkina Anna , Stekolschikova Elena , Kurochkin Ilia , Mazzarino Randall , Duval Nathan , Zubkov Dmitri , Giavalisco Patrick , Wilkinson Terry G. , Patterson David , Khaitovich Philipp , Pääbo Svante
Published: May 2020

We analyze the metabolomes of humans, chimpanzees and macaques in muscle, kidney and three different regions of the brain. Whereas several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites in oxidative phosphorylation and purine biosynthesis are consistently present in lower concentrations in the brains of humans. In particular, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine synthesis, occur at lower concentrations in humans. This enzyme carries an amino acid substitution that is present in all humans today but absent in Neandertals. By introducing the modern human substitution into the genomes of mice, as well as the ancestral, Neandertal-like substitution into the genomes of human cells, we show that this amino acid substitution is responsible for much or all of the reduction ofde novosynthesis of purines in humans.
Development of caecaloids to study host-pathogen interactions: new insights into immunoregulatory functions ofTrichuris murisextracellular vesicles in the caecum
Authors: Duque-Correa María A. , Schreiber Fernanda , Rodgers Faye H. , Goulding David , Forrest Sally , White Ruby , Buck Amy , Grencis Richard K. , Berriman Matthew
Published: May 2020

The caecum, an intestinal appendage in the junction of the small and large intestines, displays a unique epithelium that serves as an exclusive niche for a range of pathogens including whipworms (Trichuris spp). While protocols to grow organoids from small intestine (enteroids) and colon (colonoids) exist, the conditions to culture organoids from the caecum have yet to be described. Here, we report methods to grow, differentiate and characterise mouse adult stem cell-derived caecal organoids, termed caecaloids. We compare the cellular composition of caecaloids to that of enteroids identifying differences in intestinal epithelial cell (IEC) populations that mimic those found in the caecum and small intestine. The remarkable similarity in the IECs composition and spatial conformation of caecaloids and their tissue of origin enables their use as anin vitromodel to study host interactions with important caecal pathogens. Thus, exploiting this system we investigated the responses of caecal IECs to extracellular vesicles (EVs) secreted/excreted by the intracellular helminthTrichuris muris.Our findings reveal novel immunoregulatory effects of whipworm EVs on the caecal epithelium, including the downregulation of responses to nucleic acid recognition and type-I interferon (IFN) signalling.
GABAA receptor mapping in human using non-invasive electrophysiology
Authors: Shaw Alexander D , Chandler Hannah L , Hamandi Khalid , Muthukumaraswamy Suresh D , Hammers Alexander , Singh Krish D
Published: May 2020

The non-invasive study of cortical oscillations provides a window onto neuronal processing. Temporal correlation of these oscillations between distinct anatomical regions is considered a marker of functional connectedness. As the most abundant inhibitory neurotransmitter in the mammalian brain, γ-aminobutyric acid (GABA) is thought to play a crucial role in shaping the frequency and amplitude of oscillations, which thereby suggests a role for GABA in shaping the topography of functional activity and connectivity. This study explored the effects of pharmacologically blocking the reuptake of GABA (increasing local concentrations) through oral administration of the GABA transporter 1 (GAT1) blocker tiagabine (15 mg). We show that the spatial distribution of tiagabine-induced activity changes, across the brain, corresponds to group-average flumazenil PET maps of GABAA receptor distribution.

In a placebo-controlled crossover design, we collected resting magnetoencephalography (MEG) recordings from 15 healthy male individuals prior to, and at 1-, 3- and 5- hours post, administration of tiagabine and placebo pill. Using leakage-corrected amplitude envelope correlations (AECs), we quantified the functional connectivity in discrete frequency bands across the whole brain, using the 90-region Automatic Anatomical Labelling atlas (AAL90), as well as quantifying the average oscillatory activity across the brain.

Analysis of variance in connectivity using a drug-by-session (2×4) design revealed interaction effects, accompanied by main effects of drug and session. Post-hoc permutation testing of each post-drug recording against the respective pre-drug baseline revealed consistent reductions of a bilateral occipital network spanning theta, alpha and beta frequencies, and across 1- 3- and 5- hour recordings following tiagabine, but not placebo.

The same analysis applied to activity, across the brain, also revealed a significant interaction, with post-hoc permutation testing demonstrating significant increases in activity across frontal regions, coupled with reductions in activity in posterior regions, across the delta, theta, alpha and beta frequency bands.

Crucially, we show that the spatial distribution of tiagabine-induced changes in oscillatory activity overlap significantly with group-averaged maps of the estimated distribution of GABAA receptors, derived from scaled flumazenil volume-of-distribution (FMZ-VT) PET, hence demonstrating a possible mechanistic link between GABA availability, GABAA receptor distribution, and low-frequency network oscillations. We therefore propose that electrophysiologically-derived maps of oscillatory connectivity and activity can be used as sensitive, time-resolved, and targeted receptor-mapping tools for pharmacological imaging at the group level, providing direct measures of target engagement and pharmacodynamics.
Predicting drug-target interactions using multi-label learning with community detection method (DTI-MLCD)
Authors: Chu Yanyi , Shan Xiaoqi , Salahub Dennis R. , Xiong Yi , Wei Dong-Qing
Published: May 2020

Identifying drug-target interactions (DTIs) is an important step for drug discovery and drug repositioning. To reduce heavily experiment cost, booming machine learning has been applied to this field and developed many computational methods, especially binary classification methods. However, there is still much room for improvement in the performance of current methods. Multi-label learning can reduce difficulties faced by binary classification learning with high predictive performance, and has not been explored extensively. The key challenge it faces is the exponential-sized output space, and considering label correlations can help it. Thus, we facilitate the multi-label classification by introducing community detection methods for DTIs prediction, named DTI-MLCD. On the other hand, we updated the gold standard data set proposed in 2008 and still in use today. The proposed DTI-MLCD is performed on the gold standard data set before and after the update, and shows the superiority than other classical machine learning methods and other benchmark proposed methods, which confirms the efficiency of it. The data and code for this study can be found athttps://github.com/a96123155/DTI-MLCD.
RippleNet: A Recurrent Neural Network for Sharp Wave Ripple (SPW-R) Detection
Authors: Hagen Espen , Chambers Anna R. , Einevoll Gaute T. , Pettersen Klas H. , Enger Rune , Stasik Alexander J.
Published: May 2020

Hippocampal sharp wave ripples (SPW-R) have been identified as key bio-markers of important brain functions such as memory consolidation and decision making. SPW-R detection typically relies on hand-crafted feature extraction, and laborious manual curation is often required. In this multidisciplinary study, we propose a novel, self-improving artificial intelligence (AI) method in the form of deep Recurrent Neural Networks (RNN) with Long Short-Term memory (LSTM) layers that can learn features of SPW-R events from raw, labeled input data. The algorithm is trained using supervised learning on hand-curated data sets with SPW-R events. The input to the algorithm is the local field potential (LFP), the low-frequency part of extracellularly recorded electric potentials from the CA1 region of the hippocampus. The output prediction can be interpreted as the time-varying probability of SPW-R events for the duration of the input. A simple thresholding applied to the output probabilities is found to identify times of events with high precision. The reference implementation of the algorithm, named ‘RippleNet’, is open source, freely available, and implemented using a common open-source framework for neural networks (tensorflow.keras) and can be easily incorporated into existing data analysis workflows for processing experimental data.
Hunting with catapults: the predatory strike of the dragonfly larva
Authors: Büsse Sebastian , Koehnsen Alexander , Rajabi Hamed , Gorb Stanislav N.
Published: May 2020

Dragonfly larvae capture their prey with a strongly modified -extensible- mouthpart using a biomechanically unique but not yet understood mechanism. The current opinion of hydraulic pressure being the driving force of the predatory strike can be refuted by our manipulation experiments and reinterpretation of former studies. On this fact, we present evidence for a synchronized dual-catapult system powered by two spring-loaded catapults. The power output of the system exceeds generally the maximum power achievable by musculature. Energy for the movement is stored by straining a resilin-containing structure at each joint and possibly the surrounding cuticle which is preloaded by muscle contraction. To achieve the precise timing required to catch fast-moving prey, accessory structures are used to lock and actively trigger the system, ensuring the synchronisation of both catapults. As a proof of concept, we developed a bio-inspired robotic arm resembling the morphology and functional principle of the extensible mouthpart. Our study elucidates the predatory strike of dragonfly larvae by proposing a novel mechanism, where two synchronized catapults power the ballistic movement of prey capturing in dragonfly larvae – a so-called synchronized dual-catapult system. Understanding this complex biomechanical system may further our understanding in related fields of bio inspired robotics and biomimetics.

One Sentence Summary

The synchronized dual-catapult, a biomechanically novel mechanism for the ballistic movement of prey capturing in dragonfly larvae
ctmmweb: A graphical user interface for autocorrelation-informed home range estimation
Authors: Calabrese Justin M. , Fleming Christen H. , Noonan Michael J. , Dong Xianghui
Published: May 2020

Estimating animal home ranges is a primary purpose of collecting tracking data. All conventional home range estimators in widespread usage, including minimum convex polygons and kernel density estimators, assume independently sampled data. In stark contrast, modern GPS animal tracking datasets are almost always strongly autocorrelated. This incongruence between estimator assumptions and empirical reality leads to systematically underestimated home ranges. Autocorrelated kernel density estimation (AKDE) resolves this conflict by modeling the observed autocorrelation structure of tracking data during home range estimation, and has been shown to perform accurately across a broad range of tracking datasets. However, compared to conventional estimators, AKDE requires additional modeling steps and has heretofore only been accessible via the command-linectmmR package. Here, we introducectmmweb, which provides a point-and-click graphical interface toctmm, and streamlines AKDE, its prerequisite autocorrelation modeling steps, and a number of additional movement analyses. We demonstratectmmweb’scapabilities, including AKDE home range estimation and subsequent home range overlap analysis, on a dataset of four jaguars from the Brazilian Pantanal. We intendctmmwebto open AKDE and related autocorrelation-explicit analyses to a wider audience of wildlife and conservation professionals.
Deubiquitinating Enzyme Amino Acid Profiling Reveals a Class of Ubiquitin Esterases
Authors: De Cesare Virginia , Lopez Daniel Carbajo , Mabbitt Peter D. , Antico Odetta , Wood Nicola T. , Virdee Satpal
Published: May 2020

The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome and many have been implicated with pathologies including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct and its physiological importance is emerging. Here we couple chemically and chemoenzymatically synthesized ubiquitinated lysine and threonine model substrates to a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry-based DUB assay. Using this platform, we profile two-thirds of known catalytically active DUBs for threonine esterase and lysine isopeptidase activity and find that most DUBs demonstrate dual selectivity. However, with two anomalous exceptions, the ovarian tumor domain (OTU) DUB class demonstrate specific (iso)peptidase activity. Strikingly, we find the Machado Josephin Domain (MJD) class to be unappreciated non-lysine DUBs with highly specific ubiquitin esterase activity that rivals the efficiency of the most active isopeptidases. Esterase activity is dependent on the canonical catalytic triad but proximal hydrophobic residues appear to be general determinants of non-lysine activity. These findings suggest that non-lysine ubiquitination is an integral component of the ubiquitin system, with regulatory sophistication comparable to that of canonical ubiquitination.
Leaf shape and size variation in bur oaks: An empirical study and simulation of sampling strategies
Authors: Desmond Sara C. , Garner Mira , Flannery Seamus , Whittemore Alan T. , Hipp Andrew L.
Published: May 2020

PREMISE

Leaf shape and size figure strongly in trees’ adaptation to their environments. Oaks are notoriously variable in leaf morphology. Our study examines the degree to which within-tree, among-tree, and among-site variation contribute to latitudinal variation in leaf shape and size of bur oak (Quercus macrocarpa: Fagaceae), one of North America’s most geographically widespread oak species.

METHODS

Samples were collected from four sites each at northern, central, and southern latitudes of the bur oak range. Ten leaf size traits were measured, and variance in these traits and eight ratios based on these traits was partitioned into tree, population, and latitude components. We then parameterized a series of leaf collection simulations using empirical covariance among leaves on trees and trees at sites. We used the simulations to assess the efficiency of different collecting strategies for estimating among-population differences in leaf shape and size.

KEY RESULTS

Leaf size measurements were highly responsive to latitude. Site contributed more than tree to total variation in leaf morphology. Simulations suggest that power to detect among-site variance in leaf shape and size can be estimated most efficiently with increases in either leaves per tree (10-11 leaves from each of 5 trees) or trees per site (5 leaves from each of 10+ trees).

CONCLUSIONS

Our study demonstrates the utility of simulating sampling and controlling for variance in sampling for leaf morphology, whether the questions being addressed are ecological, evolutionary, or taxonomic. Simulation code is provided as an R package (traitsPopSim) to help researchers plan morphological sampling strategies.
Somatostatin, anIn VivoBinder to Aβ Oligomers, Binds to βPFOAβ(1-42)Tetramer
Authors: Puig Eduard , Tolchard James , Riera Antoni , Carulla Natàlia
Published: May 2020

Somatostatin (SST14) is strongly related to Alzheimer’s disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomersin vivo. Recently, the 3D structure of a membrane-associated β-sheet pore forming tetramer (βPFOAβ(1-42)tetramer) has been reported. Here we show that SST14 binds selectively to the βPFOAβ(1-42)tetramer without binding to monomeric Aβ(1-42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1-42)tetramer and are in agreement with a 2:1 stoichiometry determined by both native MS and ITC. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade, as well as positions the βPFOAβ(1-42)tetramer as a relevant aggregation form of Aβ and as a potential target for AD.