bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing the ecology of a Jurassic pseudoplanktonic raft colony
Authors: Hunter Aaron W. , Casenove David , Mayers Celia , Mitchell Emily G.
Published: July 2020

Pseudoplanktonic crinoid raft colonies are an enigma of the Jurassic. These raft colonies are thought to have developed as floating filter-feeding communities due to an exceptionally rich oceanic niche, high in the water column enabling them to reach large densities on these log rafts. However, this pseudoplanktonic hypothesis has not been quantitatively tested, and there remains some doubt that this mode of life was possible. The ecological structure of the crinoid colony is resolved using spatial point process analyses and the duration estimates of the floating system until sinking using moisture diffusion models. Using spatial analysis, we found that the crinoids would have trailed preferentially positioned at the back of the floating log in the regions of least resistance, consistent with a floating, not benthic ecology. Additionally, we found using a series of moisture diffusion models at different log densities and sizes that ecosystem collapse did not take place solely due to colonies becoming overladen as previously assumed. Our analyses have found that these crinoid colonies studied could have existed for more than 10 years, even up to 20 years, exceeding the life expectancy of modern documented raft systems with possible implications for the role of modern raft communities in the biotic colonization of oceanic islands and intercontinental dispersal of marine and terrestrial species.
A ratiometric fluorescent probe for pH detection based on Ag
2
S quantum dots–carbon dots nanohybrids
Authors: Lei Xiaoxue , Fu Yiying , Wu Yuan , Chen Lu , Liang Jiangong
Published: July 2020

In this study, a novel ratiometric fluorescent nanoprobe for pH monitoring has been developed by synthesizing red fluorescent Ag
2
S quantum dots (Ag
2
S QDs) and green fluorescent carbon dots (CDs) nanohybrids (Ag
2
S CDs) in one pot using CDs as templates. The nanoprobe exhibits dual-emission peaks at 500 and 670 nm under a single-excitation wavelength of 450 nm. The red fluorescence can be selectively quenched by increasing pH, while the green fluorescence is an internal reference. Therefore, the change of the relative fluorescence intensity (I
500
/I
670
) in the ratiometric Ag
2
S CDs probes can be used for pH sensing. The results revealed that I
500
/I
670
of Ag
2
S CDs probes was linearly related to pH variation between pH 5.4 and 6.8. Meanwhile, the Ag
2
S CDs probes possessed a good reversibility along with pH changing between 5.0 and 7.0 without any interruption from common metal ions, proteins and other interferences.
Are replication rates the same across academic fields? Community forecasts from the DARPA SCORE programme
Authors: Gordon Michael , Viganola Domenico , Bishop Michael , Chen Yiling , Dreber Anna , Goldfedder Brandon , Holzmeister Felix , Johannesson Magnus , Liu Yang , Twardy Charles , Wang Juntao , Pfeiffer Thomas
Published: July 2020

The Defense Advanced Research Projects Agency (DARPA) programme ‘Systematizing Confidence in Open Research and Evidence' (SCORE) aims to generate confidence scores for a large number of research claims from empirical studies in the social and behavioural sciences. The confidence scores will provide a quantitative assessment of how likely a claim will hold up in an independent replication. To create the scores, we follow earlier approaches and use prediction markets and surveys to forecast replication outcomes. Based on an initial set of forecasts for the overall replication rate in SCORE and its dependence on the academic discipline and the time of publication, we show that participants expect replication rates to increase over time. Moreover, they expect replication rates to differ between fields, with the highest replication rate in economics (average survey response 58%), and the lowest in psychology and in education (average survey response of 42% for both fields). These results reveal insights into the academic community's views of the replication crisis, including for research fields for which no large-scale replication studies have been undertaken yet.
Genetic growth potential, rather than phenotypic size, predicts migration phenotype in Atlantic salmon
Authors: Debes Paul V. , Piavchenko Nikolai , Erkinaro Jaakko , Primmer Craig R.
Published: July 2020

Knowledge of the relative importance of genetic versus environmental determinants of major developmental transitions is pertinent to understanding phenotypic evolution. In salmonid fishes, a major developmental transition enables a risky seaward migration that provides access to feed resources. In Atlantic salmon, initiation of the migrant phenotype, and thus age of migrants, is presumably controlled via thresholds of a quantitative liability, approximated by body size expressed long before the migration. However, how well size approximates liability, both genetically and environmentally, remains uncertain. We studied 32 Atlantic salmon families in two temperatures and feeding regimes (fully fed, temporarily restricted) to completion of migration status at age 1 year. We detected a lower migrant probability in the cold (0.42) than the warm environment (0.76), but no effects of male maturation status or feed restriction. By contrast, body length in late summer predicted migrant probability and its control reduced migrant probability heritability by 50–70%. Furthermore, migrant probability and length showed high heritabilities and between-environment genetic correlations, and were phenotypically highly correlated with stronger genetic than environmental contributions. Altogether, quantitative estimates for the genetic and environmental effects predicting the migrant phenotype indicate, for a given temperature, a larger importance of genetic than environmental size effects.
Contrasting size and fate of juvenile crown-of-thorns starfish linked to ontogenetic diet shifts
Authors: Wilmes Jennifer C. , Hoey Andrew S. , Pratchett Morgan S.
Published: July 2020

Population dynamics of organisms are shaped by the variation in phenotypic traits, often expressed even among individuals from the same cohort. For example, individual variation in the timing of ontogenetic shifts in diet and/or habitat greatly influences subsequent growth and survival of some organisms, with critical effects on population dynamics. Few studies of natural systems have, however, demonstrated that marked phenotypic variation in growth rates or body size among individuals within a modelled cohort is linked to dietary shifts and food availability. Population irruptions of the crown-of-thorns starfish are one of the foremost contributors to the global degradation of coral reefs, but causes of irruptions have been debated for decades. Here we demonstrate, based on extensive field sampling of juvenile starfish (
n
= 3532), that marked variation in body size among juvenile starfish is linked to an ontogenetic diet shift from coralline algae to coral. This transition in diet leads to exponential growth in juveniles and is essential for individuals to reach maturity. Because smaller individuals experience higher mortality and growth is stunted on an algal diet, the ontogenetic shift to corallivory enhances individual fitness and replenishment success. Our findings suggest that the availability of coral prey facilitates early ontogenetic diet shifts and may be fundamental in initiating population irruptions.
Body shape diversification along the benthic–pelagic axis in marine fishes
Authors: Friedman S. T. , Price S. A. , Corn K. A. , Larouche O. , Martinez C. M. , Wainwright P. C.
Published: July 2020

Colonization of novel habitats can result in marked phenotypic responses to the new environment that include changes in body shape and opportunities for further morphological diversification. Fishes have repeatedly transitioned along the benthic–pelagic axis, with varying degrees of association with the substrate. Previous work focusing on individual lineages shows that these transitions are accompanied by highly predictable changes in body form. Here, we generalize expectations drawn from this literature to study the effects of habitat on body shape diversification across 3344 marine teleost fishes. We compare rates and patterns of evolution in eight linear measurements of body shape among fishes that live in pelagic, demersal and benthic habitats. While average body shape differs between habitats, these differences are subtle compared with the high diversity of shapes found within each habitat. Benthic living increases the rate of body shape evolution and has led to numerous lineages evolving extreme body shapes, including both exceptionally wide bodies and highly elongate, eel-like forms. By contrast, we find that benthic living is associated with the slowest diversification of structures associated with feeding. Though we find that habitat can serve as an impetus for predictable trait changes, we also highlight the diversity of responses in marine teleosts to opportunities presented by major habitats.
Neural architecture and regeneration in the acoel
Hofstenia miamia
Authors: Hulett Ryan E. , Potter Deirdre , Srivastava Mansi
Published: July 2020

The origin of bilateral symmetry, a major transition in animal evolution, coincided with the evolution of organized nervous systems that show regionalization along major body axes. Studies of Xenacoelomorpha, the likely outgroup lineage to all other animals with bilateral symmetry, can inform the evolutionary history of animal nervous systems. Here, we characterized the neural anatomy of the acoel
Hofstenia miamia
. Our analysis of transcriptomic data uncovered orthologues of enzymes for all major neurotransmitter synthesis pathways. Expression patterns of these enzymes revealed the presence of a nerve net and an anterior condensation of neural cells. The anterior condensation was layered, containing several cell types with distinct molecular identities organized in spatially distinct territories. Using these anterior cell types and structures as landmarks, we obtained a detailed timeline for regeneration of the
H
.
miamia
nervous system, showing that the anterior condensation is restored by eight days after amputation. Our work detailing neural anatomy in
H
.
miamia
will enable mechanistic studies of neural cell type diversity and regeneration and provide insight into the evolution of these processes.
Quality characteristics of paprika packaged with functional film
applied by essential oil of Artemisia princeps
Pampanini
Authors: Jang Miran , Lee Eun-Ji , Chang Min-Sun , Kim Gun-Hee
Published: July 2020

The aim of this study was to verify the effect of the essential oil (EO) of
Artemisia princeps as a functional film component for
enhancing the quality of paprika during storage. EO dilutions of 0.5, 1, and
2% were used for the experiments, and the bacterial growth inhibition
effect of EO was confirmed against all tested bacteria. The paprika was packaged
in 50 μm-thick polypropylene (PP) film containing 0.5% EO and then
stored at 10°C for 21 days. To determine the effect of EO during paprika
storage, the weight loss rate, color, soluble solid content, hardness,
microorganism content, appearance, and vitamin C content were recorded for each
sample. It was found that the PP film containing EO 0.5% prevented water
loss, resulting in an improved appearance. In addition, the weight loss rate
from the paprika for this film remained unchanged, unlike in the case of the
paprika packaged in a corrugated box. In addition, the soluble solid contents,
hardness, and CO2 contents of the film containing 0.5% EO were
higher than those for the corrugated box-stored sample, thereby indicating the
positive effect of EO on sample quality maintenance. In terms of the microbial
quality assessment, the total number of aerobic bacteria and molds were lower
for the 0.5% EO film-stored sample due to the antimicrobial effect of
A. princeps. No effect was observed in terms of the vitamin
C content. The obtained results therefore suggest that the application of EO to
the PP film is effective for paprika quality preservation.
Quality characteristics, antioxidant activities and acrylamide formation in cookies added with onion peel powder
Authors: Yeom Mi-Sook , Hwang Eun-Sun
Published: July 2020

This study was conducted to investigate the quality characteristics, antioxidant activities and levels of acrylamide formation in cookies containing different amounts of onion peel powder. Onion peel powder was incorporated into the cookies at a level of 2–6% based on the total weight of wheat flour. The contents of moisture, ash, crude protein, total polyphenols, total flavonoids, and acrylamide content of cookies were determined, in addition to their antioxidant activities, pH values, loss rates, spread ratios, color, and texture. Upon increasing the amount of onion peel powder, the moisture and ash contents of the cookies increased, wheareas the pH, loss rate and spread ratio of the cookies decreased. In terms of the chromatic analysis, the L and b values decreased, while the a values increased as the amount of added onion peel powder increased. Furthermore, the total polyphenol and total flavonoid contents increased, while the antioxidant activities were significantly higher than that of the control, increasing proportionally with the concentration of onion peel powder. Moreover, the acrylamide contents of the cookies decreased slightly upon increasing the amount of added onion peel powder, with 6% onion peel powder being particularly effective in inhibiting acrylamide formation. These results suggest that the addition of onion peel powder to cookies will increase the value of cookies by enhancing their antioxidant activities and decreasing acrylamide formation.
Nutritional compositions and their retention rates of carrots by
different cooking methods
Authors: Lee Kunjong , Chung Heajung
Published: July 2020

Proximate components and mineral contents of Daucus carota L.
were investigated following cooking using 5 different methods (i.e., boiling,
pan-roasting, stir-frying, deep-fat frying, and steaming), and their retention
rates were also evaluated. Weight loss was evaluated in all cooked carrot
samples, and significant difference in (p<0.05) proximate components and
mineral contents were found upon variation in the cooking method. The highest
protein, fat, and ash contents were detected in deep-fried carrots, while a high
content was found in raw, boiled, and steamed carrots. In retention rates of
carrot by cooking method, frying sifnificantly lowered 40.89%. Mineral
(Na, Fe, Cu) retention rates were significantly lowered by boiling and steaming,
resulting in rates of 70%. Carrots were cooked by using different methods
and the retention rates of β-carotene and vitamin E according to cooking
methods of carrots were investigated., In amino acid retention rates,
deep-frying was lowest examined (Arg: 61.64%, Cys: 93.97%).
Therefore, these data can be used as a basis for the processing of carrots.
Physicochemical properties and physiological activities of acai berry extract fermented by lactic acid bacteria
Authors: Kim Ji Wan , Hong Joo-Heon
Published: July 2020

This study was conducted to investigate the physicochemical properties and physiological activities of acai berry extract fermented by lactic acid bacteria (LAB). The acai berry extract was prepared according using fermentation times ranging from 0 to 72 h. The viable cell count of lactic acid bacteria increased to 7.38 log CFU/mL after 48 h fermentation, while pH was 4.20, and the acidity had increased to 0.54%. In addition, total sugar and total anthocyanin contents were 51.50 g/100 g and 141.83 mg/L at 0 h fermentation, respectively; after 48 h, total sugar content decreased to 41.86 g/100 g, while after 72, total anthocyanin content increased to 182.74 mg/L. Furthermore, after 48 h, total phenolic, flavonoid, and proanthocyanidin contents increased to 34.74, 25.88, and 3.59 g/100 g, respectively. The DPPH and ABTS radical scavenging activities at 48 h were also determined, and these were found to be 81.25 and 83.46% at a concentration of 1,000 μg/mL, respectively. Moreover, the FRAP and reducing power of the fermented acai berry extract at 48 h were 0.97 μM and 1.10 at 1,000 μg/mL, respectively. Additional, the protective effect against oxidative stress in L132 cells was 89.60% after 48 h fermentation. The obtained results therefore suggested that fermented acai berry extract has the potential for application as a functional processing material in the food industry.
Anti-oxidant, anti-inflammatory, and anti-bacterial effects of
extracts from Elaeagnus umbellata leaves obtained using
different extract conditions
Authors: Kang Ha-Rin , Jung Jong-Kang , Park Se-Ho , Lee Jae-Yeul , Yang Seun-Ah
Published: July 2020

To investigate the optimum extraction condition for Elaeagnus
umbellata, the antioxidant, anti-inflammatory and antibacterial
effects of the extracts were assessed under different extraction conditions.
Gallic acid and kaempferol, known as major components, were quantitatively by
HPLC. Extracts of E. umbellata were examined in terms of their
DPPH and ABTS radical scavenging abilities in addition to their polyphenol and
flavonoid contents to determine their antioxidant activities. In addition, their
inhibition of nitric oxide (NO) production in LPS-stimulated RAW264.7 cells was
examined to determine their anti-inflammatory effects, and paper diffusion
assays were used to examine their anti-microbial activities against
Propionibacterium acnes, Staphylococcus
aureus, and Escherichia coli. It was found that
the extract obtained using 70% EtOH at 80°C for 6 h showed the
best radical scavenging activities (IC50; 8.64±0.31
μg/mL against DPPH, 9.44±0.48 μg/mL against ABTS) and NO
inhibition in RAW264.7 cells (39.6% at 500 μg/mL). In addition,
the extract obtained using 50–70% EtOH at 20–80°C for 6 h
exhibited an excellent antimicrobial activity (7.0±0.4, 6.5±0.5,
and 9.0±1.0 mm against P. acnes, S.
aureus, and E. coli, respectively). This extract
also contained the highest contents of gallic acid (45.60 μg/mg) and
kaempferol (1.16 μg/mg), and the highest extraction yield
(16.83%). Our data therefore confirm that the gallic acid-rich E.
umbellata extract exhibits enhanced antioxidant, anti-inflammatory,
and antimicrobial effects, and can be used as a functional food to protect
against skin aging and/or dermatological issues, such as acne and atopy.
Validation of pharmacological activity and anti-pollution effect of ethanol extract of Azadirachta indica leaf
Authors: Hyun Jin A , Lee Ji Hye , Kang Eun Bin , Kim Hyun Jeong , Kim Dong In , Park Ga Eun , Kwak Ki Sung , An Bong Jeon
Published: July 2020

In this study, we investigated the anti-oxidant, anti-inflammatory, whitening, anti-wrinkle, and anti-pollution effects of Neem tree (i.e., Azadirachta indica leaf) 70% ethanol extract. More specifically, the polyphenol content was 51.37 mg/g, and the DPPH and ABTS radical scavenging activities were 34.09 and 72.18%, respectively, at a final concentration of 1,000 μg/mL. SOD experiments showed an effect of 24.13% at a final concentration of 1,000 μg/mL. In addition, to investigate the whitening effect, the tyrosinase inhibition effect was measured, giving a value of 47.21% at a final concentration of 1,000 μg/mL. Furthermore, MTT assay experiments were carried out on macrophages (RAW 264.7) to determine the cytotoxicity using the neem tree leaf extract, it was confirmed that the cell viability was unaffected up to a concentration of 100 μg/mL. Moreover, anti-inflammatory (NO) analysis of the cells using macrophages stimulated with LPS induced an inflammatory response of 68.86%, in addition to an anti-inflammatory activity of 66.45% at a final concentration of 100 μg/mL. The iNOS protein showed an inhibition rate of 97.49% at a concentration of 100 μg/mL, and in the cytotoxicity assay (MTT assay) using keratinocytes (HaCaT), the cell viability was similar to that of the untreated control at 10 μg/mL. Western blotting analysis confirmed the inhibition rate of MMP-1. Additionally, HaCaT and CCD-986sk human skin cells were stimulated with benzo[e]pyrene, which contains fine dust and heavy metals, and then treated with neem tree extract to measure the effect of the extract on the cell viability. Indeed, the anti-pollution efficacy of the extract was confirmed. Overall, the benzo[e]pyrene-stimulated cells presented improvements of >92 and 81% for the HaCaT and CCD cells at a concentration of 25 μg/mL, while improvements were observed at a concentration of 100 μg/mL HaCaT for fine dust-stimulated cells. Moreover, HaCaT cell and CCD cells showed improvements of more than 85 and 76%, respectively. The obtained results therefore indicate that Neem tree 70% ethanol extract is expected to have value for application in cosmetics due to its pharmacological activity and its fine dust-blocking properties.
Impact of lock down relaxation on the COVID-19 epidemic trajectory in Bangladesh
Authors: Shimul Shafiun Nahin , Hussain Mofakhar , Faisel Abu Jamil , Hamid Syed Abdul
Published: July 2020

In this projection exercise, we analyzed the circumstances of the COVID-19 pandemic in Bangladesh and used multiple methods to characterize the epidemic curve. We merged several publicly available data sets for the purpose. Projections using actual Government data as of June 16, 2020 reveals that the epidemic curve for Bangladesh may be different from that of developed countries and quite similar to such curves in countries in the region. This is true, both in terms of incidence of cases (total number of cases per million population) and length of the epidemic (months to peak or flatten the epidemic curve). We find that while Bangladesh went into lockdown early, efforts to maintain lockdown at a national level was relaxed and new cases accelerated; with significant growth happening since lifting of lockdown on May 31. Our estimates indicate prevalence of COVID-19 may be between 200,000 and 600,000 towards end of the year, may take 9 months (270 days) to flatten the epidemic curve, lifting of the lockdown may have increased total cases by 60 to 100% and may have prolonged the epidemic by additional 2-3 months.
Discovery of A New Class of Integrin Antibodies for Fibrosis
Authors: Zhang Ji , Wang Tao , Saigal Ashmita , Johnson Josephine , Morrisson Jennifer , Tabrizifard Sahba , Hollingsworth Scott A. , Eddins Michael J. , Mao Wenxian , O’Neill Kim , Garcia-Calvo Margarita , Carballo-Jane Ester , Liu DingGang , Ham Taewon , Zhou Qiong , Dong Weifeng , Meng Hsien-Wei Yvonne , Hicks Jacqueline , Cai Tian-Quan , Akiyama Taro , Pinto Shirly , Cheng Alan C. , Greshock Thomas , Marquis John C. , Ren Zhao , Talukdar Saswata , Shaheen Hussam Hisham , Handa Masahisa
Published: July 2020

Lung fibrosis, or the scarring of the lung, is a devastating disease with huge unmet medical need. There are limited treatment options and its prognosis is worse than most types of cancer. We previously discovered that MK-0429 is an equipotent pan-inhibitor of all αv integrins that reduces proteinuria and kidney fibrosis in a preclinical model. In the present study, we further demonstrated that MK-0429 significantly inhibits fibrosis progression in a bleomycin-induced lung injury model. In search of newer integrin inhibitors for fibrosis, we characterized monoclonal antibodies discovered using Adimab’s yeast display platform. We identified several potent neutralizing integrin antibodies with unique human and mouse cross-reactivity. Among these, Ab-31 blocked the binding of multiple αv integrins to their ligands with IC50s comparable to those of MK-0429. Furthermore, both MK-0429 and Ab-31 suppressed integrin-mediated cell adhesion and latent TGFβ activation. In IPF patient lung fibroblasts, TGFβ treatment induced profound αSMA expression in phenotypic imaging assays and Ab-31 demonstrated superior in vitro activity at inhibiting αSMA expression, suggesting that the integrin antibody is able to modulate TGFβ action though mechanisms beyond the inhibition of latent TGFβ activation. Together, our results highlight the potential to develop newer integrin therapeutics for the treatment of fibrotic lung diseases.

One Sentence Summary

targeting integrin in lung fibrosis
Supervised and Unsupervised Classification of lncRNA Subtypes
Authors: Sen Rituparno , Fallmann Jörg , Walter Maria Emília M. T. , Stadler Peter F.
Published: July 2020

Many small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding (lncRNA) host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless there is mounting evidence that the host genes have biological functions. No obvious connections between the function of the host genes and the function of their payloads have been reported. Here we inverstigate whether there is an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNAs host genes can be distinguished based on sequence and structure features. A positive answer would imply a correlation between host genes and their payload. While the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads, this is no longer the case when only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. Our data indicate that the functions of MIRHGs and SNHGs are largely independent of the functions of their payloads. Furthermore, there is no evidence that the MIRHGs and SNHGs form coherent classes of long non-coding RNAs distinguished by features other than their payloads.
Warming indirectly increases invasion success in food webs
Authors: Sentis Arnaud , Montoya Jose M. , Lurgi Miguel
Published: July 2020

Climate warming and biological invasions are key drivers of biodiversity change. Their combined effects on ecological communities remain largely unexplored. We investigated the direct and indirect influences of warming on invasion success, and their synergistic effects on community structure and dynamics. Using size-structured food web models, we found that warming increased invasion success. The direct physiological effects of warming on invasions were minimal in comparison to indirect effects mediated by changes on food web structure and stability. Warmed communities with less connectivity, shortened food chains and reduced temporal variability were more susceptible to invasions. The directionality and magnitude of invasions effects on food webs varied across warming regimes. Warmer communities became smaller, more connected, and with more predator species when invaded than their colder counterparts. They were also less stable and their species more abundant. Considering food web structure is crucial to predict invasion success and its impacts under warming.
Integrated analysis of Xist upregulation and gene silencing at the onset of random X-chromosome inactivation at high temporal and allelic resolution
Authors: Pacini Guido , Dunkel Ilona , Mages Norbert , Mutzel Verena , Timmermann Bernd , Marsico Annalisa , Schulz Edda G
Published: July 2020

To ensure dosage compensation between the sexes, one randomly chosen X chromosome is silenced in each female cell in the process of X-chromosome inactivation (XCI). XCI is initiated during early development through upregulation of the long non-coding RNA Xist, which mediates chromosome-wide gene silencing. Cell differentiation, Xist upregulation and silencing are thought to be coupled at multiple levels to ensure inactivation of exactly one out of two X chromosomes. Here we perform an integrated analysis of all three processes through allele-specific single-cell RNA-sequencing. Specifically, we assess the onset of random XCI with high temporal resolution in differentiating mouse embryonic stem cells, and develop dedicated analysis approaches. By exploiting the inter-cellular heterogeneity of XCI onset, we identify Nanog downregulation as its main trigger and discover additional putative Xist regulators. Moreover, we confirm several predictions of the stochastic model of XCI where monoallelic silencing is thought to be ensured through negative feedback regulation. Finally, we show that genetic variation modulates the XCI process at multiple levels, providing a potential explanation for the long-known Xce effect, which leads to preferential inactivation of a specific X chromosome in inter-strain crosses. We thus draw a detailed picture of the different levels of regulation that govern the initiation of XCI. The experimental and computational strategies we have developed here will allow us to profile random XCI in more physiological contexts, including primary human cells in vivo.
Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and offers potential for smartphone-based detection of larval insecticide resistance
Authors: Buckingham Steven D. , Partridge Frederick A. , Poulton Beth C. , Miller Ben , McKendry Rachel A. , Lycett Gareth J , Sattelle David B.
Published: July 2020

Pyrethroid-impregnated nets have contributed significantly to halving the burden of malaria but resistance threatens their future efficacy and the pipeline of new insecticides is short. Here we report that an invertebrate automated phenotyping platform (INVAPP), combined with the algorithm Paragon, provides a robust system for measuring larval motility inAnopheles gambiae (and An. coluzzi)as well asAedes aegyptiwith the capacity for high-throughput screening for new larvicides. By this means, we reliably quantified both time- and concentration-dependent actions of chemical insecticides faster than using the WHO standard larval assay. We illustrate the effectiveness of the system using an established larvicide (temephos) and demonstrate its capacity for library-scale chemical screening using the Medicines for Malaria Venture (MMV) Pathogen Box library. As a proof-of-principle, this library screen identified a compound, subsequently confirmed to be tolfenpyrad, as an effective larvicide. We have also used the INVAPP / Paragon system to compare responses in larvae derived from WHO classified deltamethrin resistant and sensitive mosquitoes. We show how this approach to monitoring larval response to insecticides can be adapted for use with a smartphone camera application and therefore has potential for further development as a simple portable field-assay with associated real-time, geo-located information to identify hotspots.

Author summary

We have developed an automated platform for recording the motility of mosquito larvae and applied it to larvae of a mosquito vector of malaria and a mosquito vector of dengue, Zika, yellow fever and other human diseases. The platform facilitates high-throughput, chemical screening for new compounds to control mosquito larvae and also detects differences in response in larval progeny from pryethroid resistant adult mosquitoes. Pyrethroid-impregnated bednets have helped to halve the deaths from malaria in recent years but pyrethroid resistance is an important threat to this progress. Our approach assays insecticide actions faster than the current WHO standard test and we show that it can be adapted for use with a smartphone, which offers the prospect of a future field assay to monitor developing resistance associated with behavioural response with the added benefit of precise satellite-based location.
MCM10 compensates for Myc-induced DNA replication stress in breast cancer stem-like cells
Authors: Murayama Takahiko , Takeuchi Yasuto , Yamawaki Kaoru , Natsume Toyoaki , Marcela Rojas-Chaverra N. , Nishimura Tatsunori , Kogure Yuta , Nakata Asuka , Tominaga Kana , Sasahara Asako , Yano Masao , Ishikawa Satoko , Ohta Tetsuo , Ikeda Kazuhiro , Horie-Inoue Kuniko , Inoue Satoshi , Seki Masahide , Suzuki Yutaka , Sugano Sumio , Enomoto Takayuki , Tanabe Masahiko , Tada Kei-ichiro , Kanemaki Masato T. , Okamoto Koji , Tojo Arinobu , Gotoh Noriko
Published: July 2020

Cancer stem-like cells (CSCs) are responsible for the drug resistance of tumors and recurrence while they experience DNA replication stress. However, the underlying mechanisms that cause DNA replication stress in CSCs and how they compensate for this stress remain unclear. Here we provide evidence that upregulated c-Myc expression induces stronger DNA replication stress in patient-derived breast CSCs than in differentiated cancer cells. Our results suggest critical roles for mini-chromosome maintenance protein 10 (MCM10), which is a firing (activating) factor of the DNA replication origins, to compensate for the DNA replication stress. Expression levels of MCM10 are upregulated in CSCs and maintained by c-Myc. c-Myc-dependent collisions may take place between RNA transcription and DNA replication machinery in nuclei, thereby causing DNA replication stress. MCM10 may activate dormant replication origins close to the collisions to ensure replication progression. Moreover, patient-derived breast CSCs were dependent on MCM10 for their maintenance even after enrichment for CSCs that were resistant to paclitaxel, the standard chemotherapeutic agent. In addition, MCM10 depletion decreased the growth of cancer cells but not normal cells. Therefore, MCM10 is likely to robustly compensate for DNA replication stress and facilitate genome duplication in the S-phase in cancer cells, which is more pronounced in CSCs. We provide a preclinical rationale to target the c-Myc-MCM10 axis to prevent drug resistance and recurrence.
Sleep loss drives brain region- and cell type-specific alterations in ribosome-associated transcripts involved in synaptic plasticity and cellular timekeeping
Authors: Puentes-Mestril Carlos , Delorme James , Donnelly Marcus , Popke Donald , Jiang Sha , Aton Sara J.
Published: July 2020

Sleep and sleep loss are thought to impact synaptic plasticity, and recent studies have shown that sleep and sleep deprivation (SD) differentially affect gene transcription and protein translation in the mammalian forebrain. However, much less is known regarding how sleep and SD affect these processes in different microcircuit elements within the hippocampus and neocortex - for example, in inhibitory vs. excitatory neurons. Here we use translating ribosome affinity purification (TRAP) andin situhybridization to characterize the effects of sleep vs. SD on abundance of ribosome-associated transcripts in Camk2a-expressing (Camk2a+) pyramidal neurons and parvalbumin-expressing (PV+) interneurons in mouse hippocampus and neocortex. We find that while both Camk2a+ neurons and PV+ interneurons in neocortex show concurrent SD-driven increases in ribosome-associated transcripts for activity-regulated effectors of plasticity and transcriptional regulation, these transcripts are minimally affected by SD in hippocampus. Similarly we find that while SD alters several ribosome-associated transcripts involved in cellular timekeeping in neocortical Camk2a+ and PV+ neurons, effects on circadian clock transcripts in hippocampus are minimal, and restricted to Camk2a+ neurons. Taken together, our results indicate that SD effects on transcripts destined for translation are both cell type- and brain region-specific, and that these effects are substantially more pronounced in the neocortex than the hippocampus. We conclude that SD-driven alterations in the strength of synapses, excitatory-inhibitory balance, and cellular timekeeping are likely more heterogeneous than previously appreciated.

Significance Statement

Sleep loss-driven changes in transcript and protein abundance have been used as a means to better understand the function of sleep for the brain. Here we use translating ribosome affinity purification (TRAP) to characterize changes in abundance of ribosome-associated transcripts in excitatory and inhibitory neurons in mouse hippocampus and neocortex after a brief period of sleep or sleep loss. We show that these changes are not uniform, but are generally more pronounced in excitatory neurons than inhibitory neurons, and more pronounced in neocortex than in hippocampus.
Distributed Sampling-based Bayesian Inference in Coupled Neural Circuits
Authors: Zhang Wen-Hao , Lee Tai Sing , Doiron Brent , Wu Si
Published: July 2020

The brain performs probabilistic inference to interpret the external world, but the underlying neuronal mechanisms remain not well understood. The stimulus structure of natural scenes exists in a high-dimensional feature space, and how the brain represents and infers the joint posterior distribution in this rich, combinatorial space is a challenging problem. There is added difficulty when considering the neuronal mechanics of this representation, since many of these features are computed in parallel by distributed neural circuits. Here, we present a novel solution to this problem. We study continuous attractor neural networks (CANNs), each representing and inferring a stimulus attribute, where attractor coupling supports sampling-based inference on the multivariate posterior of the high-dimensional stimulus features. Using perturbative analysis, we show that the dynamics of coupled CANNs realizes Langevin sampling on the stimulus feature manifold embedded in neural population responses. In our framework, feedforward inputs convey the likelihood, reciprocal connections encode the stimulus correlational priors, and the internal Poisson variability of the neurons generate the correct random walks for sampling. Our model achieves high-dimensional joint probability representation and Bayesian inference in a distributed manner, where each attractor network infers the marginal posterior of the corresponding stimulus feature. The stimulus feature can be read out simply with a linear decoder based only on local activities of each network. Simulation experiments confirm our theoretical analysis. The study provides insight into the fundamental neural mechanisms for realizing efficient high-dimensional probabilistic inference.
Closing Gaps But Increasing Bias In North American Butterfly Inventory Completeness
Authors: Shirey Vaughn , Belitz Michael W. , Barve Vijay , Guralnick Robert
Published: July 2020

Aggregate biodiversity data from museum specimens and community observations have promise for macroscale ecological analyses. Despite this, many groups are under-sampled, and sampling is not homogeneous across space. Here we used butterflies, the best documented group of insects, to examine inventory completeness across North America. We separated digitally accessible butterfly records into those from natural history collections and burgeoning community science observations to determine if these data sources have differential spatio-taxonomic biases. When we combined all data, we found startling under-sampling in regions with the most dramatic trajectories of climate change and across biomes. We also found support for the hypothesis that community science observations are filling more gaps in sampling but are more biased towards areas with the highest human footprint. Finally, we found that both types of occurrences have familial-level taxonomic completeness biases, in contrast to the hypothesis of less taxonomic bias in natural history collections data. These results suggest that higher inventory completeness, driven by rapid growth of community science observations, is partially offset by higher spatio-taxonomic biases. We use the findings here to provide recommendations on how to alleviate some of these gaps in the context of prioritizing global change research.
Increased processing of SINE B2 non coding RNAs unveils a novel type of transcriptome de-regulation underlying amyloid beta neuro-pathology
Authors: Cheng Yubo , Gollen Babita , Saville Luke , Isaac Christopher , Mehla Jogender , Mohajerani Majid , Zovoilis Athanasios
Published: July 2020

More than 97% of the mammalian genome is non-protein coding, and repetitive elements account for more than 50% of noncoding space. However, the functional importance of many non-coding RNAs generated by these elements and their connection with pathologic processes remains elusive. We have previously shown that B2 RNAs, a class of non-coding RNAs that belong to the B2 family of SINE repeats, mediate the transcriptional activation of stress response genes (SRGs) upon application of a stimulus. Notably, B2 RNAs bind RNA Polymerase II (RNA Pol II) and suppress SRG transcription during pro-stimulation state. Upon application of a stimulus, B2 RNAs are processed into fragments and degraded, which in turn releases RNA Pol II from suppression and upregulates SRGs. Here, we demonstrate a novel role for B2 RNAs in transcriptome response to amyloid beta toxicity and pathology in the mouse hippocampus. In healthy hippocampi, activation of SRGs is followed by a transient upregulation of pro-apoptotic factors, such as p53 and miRNA-34c, which target SRGs creating a negative feedback loop that facilitates transition to the pro-stimulation state. Using an integrative RNA genomics approach, we show that in mouse hippocampi of an amyloid precursor protein knock-in mouse model and in anin vitrocell culture model of amyloid beta toxicity, this regulatory loop is dysfunctional due to increased levels of B2 RNA processing, constitutively elevated SRG expression and high p53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in cells, and is upregulated during amyloid toxicity accelerating the processing of SINE RNAs and SRG hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer’s disease (AD). This data attributes a role to SINE RNA processing in a pathological process as well as a new function to Hsf1 that is independent of its transcription factor activity.
Flight morphology and visual obstruction predict collision risk in birds
Authors: Jackson Erin K. , Elmore Jared A. , Loss Scott R. , Winger Benjamin M. , Dakin Roslyn
Published: July 2020

Collisions with buildings are a major source of mortality for wild birds, but these instantaneous events are difficult to observe. As a result, the mechanistic causes of collision mortality are poorly understood. Here, we evaluate whether sensory and biomechanical traits can explain why some species are more collision-prone than others. We first examined concordance of species vulnerability estimates across previous North American studies to determine whether these estimates are repeatable, and whether vulnerability is more similar among closely-related species. We found moderate concordance and phylogenetic signal, indicating that some bird species are consistently more collision-prone than others. We next tested whether morphological traits related to flight performance and sensory guidance explain these differences among species. Our comparative analysis shows that two traits primarily predict collision vulnerability within passerines: relative beak length and relative wing length. Small passerine species with relatively short wings and those with relatively long beaks are more collision-prone, suggesting that greater maneuverability and obstructed vision contribute to risk. Together, these findings can help inform mitigation strategies and predict which species will be most at risk in other regions.
Regulated assembly of the ER membrane protein complex
Authors: Pleiner Tino , Januszyk Kurt , Tomaleri Giovani Pinton , Oania Robert S. , Hazu Masami , Sweredoski Michael J. , Moradian Annie , Guna Alina , Voorhees Rebecca M.
Published: July 2020

The assembly of nascent proteins into multi-subunit complexes is tightly regulated to maintain cellular homeostasis. The ER membrane protein complex (EMC) is an essential insertase that requires seven membrane-spanning and two soluble subunits for function. Here we show that the kinase With no lysine 1 (WNK1), known for its role in hypertension and neuropathy, is required for assembly of the human EMC. WNK1 uses a conserved amphipathic helix to stabilize the soluble subunit, EMC2, by binding to the EMC2-8 interface. Shielding this hydrophobic surface prevents promiscuous interactions of unassembled EMC2 and precludes binding of ubiquitin ligases, permitting assembly. Using biochemical reconstitution, we show that after EMC2 reaches the membrane, its interaction partners within the EMC displace WNK1, and similarly shield its exposed hydrophobic surfaces. This work describes an unexpected role for WNK1 in protein biogenesis, and defines the general requirements of an assembly factor that will apply across the proteome.
Discovery of potential imaging and therapeutic targets for severe inflammation in COVID-19 patients
Authors: Lee Hyunjong , Im Hyung-Jun , Na Kwon Joong , Choi Hongyoon
Published: July 2020

The COVID-19 pandemic has caused more than 540,000 deaths globally. Hyperinflammation mediated by dysregulated monocyte/macrophage function is considered to be the key factor that triggers severe illness in COVID-19. However, no specific targeting molecule has been identified for detecting or treating hyperinflammation related to dysregulated macrophages in severe COVID-19. Herein, we suggest candidate targets for imaging and therapy in severe COVID-19 by analyzing single-cell RNA-sequencing data based on bronchoalveolar lavage fluid of COVID-19 patients. We found that expression ofSLC2A3, which can be imaged by [18F]fluorodeoxyglucose, was higher in macrophages from severe COVID-19 patients. Furthermore, by integrating the surface target database and drug-target binding database with RNA-sequencing data of severe COVID-19, we identifiedCCR1andFPR1as surface and druggable targets for drug delivery as well as molecular imaging. Our results provide a resource for candidate targets in the development of specific imaging and therapy for COVID-19-related hyperinflammation.
Central Nervous System Manifestations in COVID-19 Patients: A Systematic Review and Meta-analysis
Authors: Nazari Shahrzad , Jafari Amirhossein Azari , Mirmoeeni Seyyedmohammadsadeq , Sadeghian Saeid , Heidari Mohammad Eghbal , Sadeghian Siavash , Asarzadegan Farhad , Puormand Seyed Mahmoud , Alikhani Katayoun , Ebadi Hamid , Fathi Davood , Dalvand Sahar
Published: July 2020

Background

At the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID-19 initially reported in China, and later known as COVID-19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID-19. In this study, we aimed to evaluate the CNS presentations in COVID-19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic.

Methods

In this systematic review and meta-analysis, we searched PubMed, Web of Science, Ovid, Embase, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between January 1st, 2020, to April 20th, 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456).

Results

Of 2353 retrieved studies, we selected 64 studies with 11282 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID-19 were Headache (8.69%, 95%CI: 6.76%-10.82%), Dizziness (5.94%, 95%CI: 3.66%-8.22%), and Impaired consciousness (1.9%, 95%CI: 1%-2.79%).

Conclusions

The growing number of studies have reported COVID-19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID-19 can help us for better diagnosis and ultimately prevention of worse outcomes.