bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Authors: Leppek Kathrin , Byeon Gun Woo , Kladwang Wipapat , Wayment-Steele Hannah K. , Kerr Craig H. , Xu Adele F. , Kim Do Soon , Topkar Ved V. , Choe Christian , Rothschild Daphna , Tiu Gerald C. , Wellington-Oguri Roger , Fujii Kotaro , Sharma Eesha , Watkins Andrew M. , Nicol John J. , Romano Jonathan , Tunguz Bojan , Participants Eterna , Barna Maria , Das Rhiju 
Published: March 2021

SUMMARYTherapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop a new RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that “superfolder” mRNAs can be designed to improve both stability and expression that are further enhanced through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
Extensive aquatic subsidies lead to territorial breakdown and high density of an apex predator
Authors: Eriksson Charlotte E. , Kantek Daniel L.Z. , Miyazaki Selma S. , Morato Ronaldo G. , dos Santos-Filho Manoel , Ruprecht Joel S. , Peres Carlos A. , Levi Taal 
Published: March 2021

AbstractEnergetic subsidies between terrestrial and aquatic ecosystems can strongly influence food webs and population dynamics. Our objective was to study how aquatic subsidies affected jaguar (Panthera onca) diet, sociality, and population density in a seasonally flooded protected area in the Brazilian Pantanal. The diet (n = 138 scats) was dominated by fish (46%) and aquatic reptiles (55%), representing the first jaguar population known to feed extensively on fish and to minimally consume mammals (11%). These aquatic subsidies supported the highest jaguar population density estimate to date (12.4 per 100 km2) derived from camera traps (8,065 trap nights) and GPS collars (n = 13). Contrary to their mostly solitary behavior elsewhere, we documented social interactions previously unobserved between same-sex adults including cooperative fishing, co-traveling, and play. Our research demonstrates that aquatic subsidies seen in omnivores can be highly influential to obligate carnivores leading to high population density and altered social structure.
Influence of short-term temperature drops on sex-determination in sea turtles
Authors: Porter Ellen , Booth David T. , Limpus Colin J. 
Published: March 2021

ABSTRACTAll sea turtles exhibit temperature-dependent sex-determination, where warmer temperatures produce mostly females and cooler temperatures produce mostly males. As global temperatures continue to rise, sea turtle sex-ratios have become increasingly female-biased, threatening the long-term viability of many populations. Nest temperatures are dependent on sand temperature, and heavy rainfall events reduce sand temperatures for a brief period. However, it is unknown whether these short-term temperature drops are large and long enough to produce male hatchlings. To discover if short-term temperature drops within the sex-determining period can lead to male hatchling production, we exposed green and loggerhead turtle eggs to short-term temperature drops conducted in constant temperature rooms. We dropped incubation temperature at four different times during the sex-determining period for a duration of either 3 or 7 days to mimic short-term drops in temperature caused by heavy rainfall in nature. Some male hatchlings were produced when exposed to temperature drops for as little as 3 days, but the majority of male production occurred when eggs were exposed to 7 days of lowered temperature. More male hatchlings were produced when the temperature drop occurred during the middle of the sex-determining period in green turtles, and the beginning and end of the sex-determining period in loggerhead turtles. Inter-clutch variation was evident in the proportion of male hatchlings produced, indicating that maternal and or genetic factors influence male hatchling production. Our findings have management implications for the long-term preservation of sea turtles on beaches that exhibit strongly female-biased hatchling sex-ratios.
Performance of early warning signals for disease re-emergence: a case study on COVID-19 data
Authors: Proverbio Daniele , Kemp Françoise , Magni Stefano , Gonçalves Jorge 
Published: March 2021

AbstractDeveloping tools for rapid and early detection of disease re-emergence is important to perform science-based risk assessment of epidemic threats. In the past few years, several early warning signals (EWS) from complex systems theory have been introduced to detect impending critical transitions and extend the set of indicators. However, it is still debated whether they are generically applicable or potentially sensitive to some dynamical characteristics such as system noise and rates of approach to critical parameter values. Moreover, testing on empirical data has, so far, been limited. Hence, verifying EWS performance remains a challenge. In this study, we tackle this question by analyzing the performance of common EWS, such as increasing variance and autocorrelation, in detecting the emergence of COVID-19 outbreaks in various countries. We illustrate that EWS are successful in detecting disease emergence if some basic assumptions are satisfied: a slow forcing through the transitions and not-fat-tailed noise. In uncertain cases, noise properties or commensurable time scales may obscure the expected early warning signals. Overall, our results suggest that EWS can be useful for active monitoring of epidemic dynamics, but that their performance is sensitive to certain features of the underlying dynamics. Our findings thus pave a connection between theoretical and empirical studies, constituting a further step towards the application of EWS indicators for informing public health policies.Author summaryTo extend the toolkit of alerting indicators against the emergence of infectious diseases, recent studies have suggested the use of generic early warning signals (EWS) from the theory of dynamical systems. Although extensively investigated theoretically, their empirical performance has still not been fully assessed. We contribute to it by considering the emergence of subsequent waves of COVID-19 in several countries. We show that, if some basic assumptions are met, EWS could be useful against new outbreaks, but they fail to detect rapid or noisy shifts in epidemic dynamics. Hence, we discuss the potentials and limitations of such indicators, depending on country-specific dynamical characteristics and on data collection strategies.
Broad variation in rates of polyploidy and dysploidy across flowering plants is correlated with lineage diversification
Authors: Zhan Shing H. , Otto Sarah P. , Barker Michael S. 
Published: March 2021

ABSTRACTChanges in chromosome number are considered an important driver of diversification in angiosperms. Single chromosome number changes caused by dysploidy may produce strong reproductive barriers leading to speciation. Polyploidy, or whole genome duplication, yields new species that are often reproductively isolated from progenitors and may exhibit novel morphology or ecology that may further facilitate diversification. Here, we examined the rates of polyploidy, dysploidy, and diversification across the angiosperms. Our analyses of nearly 30,000 taxa representing 46 orders and 147 families found that rates of polyploidy and dysploidy differed by two to three orders of magnitude. The rates of polyploidy and dysploidy were positively correlated with diversification rates, but relative importance analyses indicated that variation in polyploidy was better correlated with diversification rates than dysploidy. Our results provide an overview of angiosperm chromosomal evolution and a roadmap for future research on the complex relationships among polyploidy, dysploidy, and diversification.
Perivascular tenascin C triggers sequential activation of macrophages and endothelial cells to generate a pro-metastatic vascular niche in the lungs
Authors: Hongu Tsunaki , Pein Maren , Insua-Rodriguez Jacob , Meier Jasmin , Decker Kristin , Descot Arnaud , Riedel Angela , Oskarsson Thordur 
Published: March 2021

ABSTRACTWhen cancers progress to metastasis, disseminated cancer cells frequently lodge near vasculature in secondary organs. However, our understanding of the cellular crosstalk evoked at perivascular sites is still rudimentary. In this study, we identify intercellular machinery governing formation of a pro-metastatic vascular niche during breast cancer colonization in lungs. We show that four secreted factors, INHBB, SCGB3A1, OPG and LAMA1, induced in metastasis-associated endothelial cells (ECs), are essential components of the vascular niche and promote metastasis in mice by enhancing stem cell properties and survival ability of cancer cells. Notably, blocking VEGF, a key regulator of EC behavior, dramatically suppressed EC proliferation, whereas no impact was observed on the expression of the four vascular niche factors in lung ECs. However, perivascular macrophages, activated via the TNC-TLR4 axis, were shown to be crucial for EC-mediated production of niche components. Together, our findings provide mechanistic insights into the formation of vascular niches in metastasis.
16S rRNA Amplicon Sequencing of BagwormMetisa planaWalker (Lepidoptera: Psychidae)
Authors: Ting Andrew Chung Jie , Zainal Abidin Cik Mohd Rizuan , Hamid Noor Hisham , Azzam Ghows , Salim Hasber 
Published: March 2021

AbstractThe bagwormMetisa planais one of the major pests in the oil palm plantation in Malaysia, with infestation that results in huge economical loss. Currently, the exact cause of the infestation is still undetermined. Studying the bacterial community ofM. planacould provide insight on the problem as the bacteria associated with insects often provide numerous benefits to the insect itself. Using 16S rRNA amplicon sequencing, the study was conducted to compare the composition of the bacterial communities of two larval stages (early instar stage and late instar stage) from outbreak area, as well as comparing the late instar stage larvae from non-outbreak and outbreak areas. Generally, the bacterial community was dominated byProteobacteriaandActinobacteriaphyla while theEnterobacteriaceaewas found to be the dominant family. When comparing between the early and late instar stage,Proteobacteriaphylum was found to be more abundant in the late instar stage (82.36%) than in the early instar stage (82.28%). At the family level, theEnterobacteriaceaewas slightly more abundant in late instar stage (75.46%) than in early instar stage (75.29%). The instar stage was observed to have no significant impact on the bacterial variability and showed similar bacterial community structure. When comparing between the non-outbreak area and outbreak,Proteobacteriawas significantly more abundant in the outbreak area (82.02%) than in the non-outbreak area (20.57%). However,Actinobacteriawas significantly more abundant in the non-outbreak area (76.29%) than in the outbreak area (14.16%). At the family level,Enterobacteriaceaewas more abundant in outbreak area (75.41%) than in non-outbreak area (11.67%).Microbacteriaceaewas observed to be more abundant in the non-outbreak area (70.87%) than in the outbreak area (12.47%). Although the result showed no significant difference in bacterial variability between different areas, it the bacterial community structure was significantly different.
The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype
Authors: Band Gavin , Leffler Ellen M. , Jallow Muminatou , Sisay-Joof Fatoumatta , Ndila Carolyne M. , Macharia Alexander W. , Hubbart Christina , Jeffreys Anna E. , Rowlands Kate , Nguyen Thuy , Goncalves Sonia M. , Ariani Cristina V. , Stalker Jim , Pearson Richard D. , Amato Roberto , Drury Eleanor , Sirugo Giorgio , D’Alessandro Umberto , Bojang Kalifa A. , Marsh Kevin , Peshu Norbert , Conway David J. , Williams Thomas N. , Rockett Kirk A. , Kwiatkowski Dominic P. 
Published: March 2021

AbstractHost genetic factors can confer resistance against malaria, raising the question of whether this has led to evolutionary adaptation of parasite populations. In this study we investigated the correlation between host and parasite genetic variation in 4,171 Gambian and Kenya children ascertained with severe malaria due toPlasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and variation in three regions of the parasite genome, including nonsynonymous variants in the acyl-CoA synthetase family memberPfACS8on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The HbS-associated parasite alleles are in strong linkage disequilibrium and have frequencies which covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome, and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in AfricanP. falciparumpopulations.
Auxin-responsive (phospho)proteome analysis reveals regulation of cell cycle and ethylene signaling during rice crown root development
Authors: Singh Harshita , Singh Zeenu , Zhu Tingting , Xu Xiangyu , Waghmode Bhairavnath , Garg Tushar , Yadav Shivani , Sircar Debabrata , De Smet Ive , Yadav Shri Ram 
Published: March 2021

AbstractThe rice root system, which primarily consists of adventitious/crown roots (AR/CR) developed from the coleoptile base, is an excellent model system for studying shoot-to-root trans-differentiation process. We reveal global changes in protein and metabolite abundance, and protein phosphorylation in response to an auxin stimulus during CR development. Global proteome and metabolome analyses of developing crown root primordia (CRP) and emerged CRs uncovered that the biological processes associated with chromatin conformational change, gene expression, and cell cycle were translationally regulated by auxin signaling. Spatial gene expression pattern analysis of differentially abundant proteins disclosed their stage-specific dynamic expression pattern during CRP development. Further, our tempo-spatial gene expression and functional analyses revealed that auxin creates a regulatory feedback module during CRP development and activates ethylene biosynthesis exclusively during CRP initiation. Ethylene signaling promotes CR formation by repressing the cytokinin response regulator,OsRR2. Additionally, the (phospho)proteome analysis identified differential phosphorylation of the Cyclin-dependent kinase G-2 (OsCDKG;2), and cell wall proteins, in response to auxin signaling, suggesting that auxin-dependent phosphorylation may be required for cell cycle activation, and cell wall synthesis during root organogenesis. Thus, our study provides evidence for the translational and post-translational regulation during CRP trans-differentiation downstream of the auxin signaling pathway.HighlightGlobal (phospho)proteome and metabolic profiling of rice CRP and CRs uncover differential proteins and metabolites associated with gene expression, cell cycle, ethylene signaling and cell wall synthesis during CR development.
Spectrogram cross-correlation can be used to measure the complexity of bird vocalizations
Authors: Sawant Suyash , Arvind Chiti , Joshi Viral , Robin V. V. 
Published: March 2021

SummaryBirdsong is an important signal in mate attraction and territorial defense. Quantifying the complexity of these songs can shed light on individual fitness, sexual selection, and behavior. Several techniques have been used to quantify song complexity and be broadly categorized into diversity indices, measures of stationary probabilities, and measures of sequential variations. However, these methods are unable to account for important acoustic features like the frequency bandwidth and the variety in the shape of syllables which are an integral part of these vocal signals. This study proposes a new complexity measure that considers intra-song note variability and calculates a weighted index for birdsongs using spectral cross-correlation.We compared the previously described methods to understand the advantages and limitations based on the factors that would be affecting the complexity of songs. We developed a new method- Note Variability Index (NVI), which incorporates the spectral features of notes while quantifying complexity. This measure alleviates the need for manual annotations of notes that can be error-prone. We used Spectrogram Cross-Correlation (SPCC) to compare notes within a song and used the output values to quantify song complexity.To check for the efficacy of the new method, we generated synthetic songs to caricature extremes in song complexity and compared selected conventional complexity measures along with the NVI. We provide case-specific limitations of these methods. Additionally, to examine the efficacy of this new method in real-world scenarios, we used natural birdsongs from multiple species across the globe with varying song structures to compare conventional methods with NVI.To our knowledge, NVI is the only song complexity method that captures the variation of spectral features of notes in songs where the conventional methods fail to distinguish between similar song structures with different note types. As NVI does not need a manual classification of notes, it can be easily implemented for any type of birdsong with existing sound analysis softwares; it is very quick, avoids the possible biases in note classification, and can possibly be automated for large datasets in the future.
Expression of Sonic Hedgehog and Pathway Components in the Embryonic Mouse Head: Anatomical Relationships Between Regulators of Positive and Negative Feedback
Authors: Sigulinsky Crystal L. , Li Xiaodong , Levine Edward M. 
Published: March 2021

ABSTRACTObjectiveThe Hedgehog pathway is a fundamental signaling pathway in organogenesis. The expression patterns of the ligandSonic Hedgehog(Shh) and key pathway components have been studied in many tissues but direct spatial comparisons across tissues with different cell compositions and structural organization are not common and could reveal tissue-specific differences in pathway dynamics.ResultsWe directly compared the expression characteristics ofShh, and four genes with functional roles in signaling and whose expression levels serve as readouts of pathway activity in multiple tissues of the embryonic mouse head at embryonic day 15.5 by serialin situhybridization. The four readout genes were the positive feedback regulatorGli1, and three negative feedback regulators,Patched1, Patched2, andHedgehog Interacting Protein. While the relative abundance ofGli1was similar across tissues, the relative expression levels and spatial distribution ofShhand the negative feedback regulators differed, suggesting that feedback regulation of hedgehog signaling is context dependent. This comparative analysis offers insight into how consistent pathway activity could be achieved in tissues with different morphologies and characteristics of ligand expression.
Unaffected functional recovery after spinal cord contusions at different circadian times
Authors: Slomnicki Lukasz P. , Wei George , Burke Darlene A. , Whittemore Scott R. , Ohri Sujata Saraswat , Hetman Michal 
Published: March 2021

AbstractThe circadian rhythms of gene expression drive diurnal oscillations of physiological processes that determine the acute injury response including immunity, inflammation and hemostasis. While outcomes of various acute injuries are affected by the time of day at which the original insult occurred, such diurnal influences on recovery after spinal cord injury (SCI) are unknown. We report that several key regulators of circadian gene expression are differentially expressed in uninjured spinal cord tissue of naïve mice at Zeitgeber time 1 (ZT1) or ZT12, where ZT0 or ZT12 are times when lights are turned on or off, respectively. However, mice that received moderate, T9 contusive SCI at ZT0 or ZT12 showed similar recovery of locomotion as determined using the ladder walking test and the Basso mouse scale (BMS) over a 6 week post-injury period. Consistent with those findings, terminal histological analysis revealed no significant differences in white matter sparing at the injury epicenter. Therefore, locomotor recovery after thoracic contusive SCI is not affected by the time of day at which the neurotrauma occurred at least when comparing the beginning to the end of the mouse active period.
Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model
Authors: Niemeyer James E. , Gadamsetty Poornima , Chun Chanwoo , Sylvester Sherika , Lucas Jacob P. , Ma Hongtao , Schwartz Theodore H. , Aksay Emre 
Published: March 2021

AbstractSeizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with multi-regional two-photon imaging of excitatory and inhibitory neuronal activity using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyper-excitation, then propagate more broadly once inhibitory restraint in the surround is overcome.TeaserWe uncover the roles of excitation and inhibition during seizures, thus opening a path to more targeted therapy of epilepsy.