bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of CDC Opioid-Prescribing Guidelines in a Community Hospital Emergency Department
Authors: Gumidyala Lalitha , Savul Sajjad A. , Shofer Frances S. , Green-McKenzie Judith
Published: March 2021

The United States continues to battle the addiction and overdose deaths with the opioid epidemic. Prescription opioids are responsible for more than half of these deaths. This before-after study was conducted to assess the effect of the Centers for Disease Control and Prevention's (CDC's) opioid prescription guidelines. Data were abstracted from electronic health records of adult patients presenting with low back pain seen in the emergency department during the study period. SAS statistical software was used to compare opioid prescription practices before and after the intervention. A total of 1006 patients were included in the analysis. Opioid prescriptions decreased by 11% post-CDC guidelines (45% vs 34%). Of patients receiving opioids (n = 383), there was a 6% reduction in the number of days (<5 days) for which opioids were prescribed post-CDC guidelines (14% vs 8%). CDC guidelines on opioid prescribing were associated with a significant reduction in opioid prescribing in terms of both quantity and length of time prescribed. Public health policies as guidelines may positively influence provider decision making and behaviors.
Current Research Priorities in Healthcare Simulation
Authors: Anton Nicholas , Calhoun Aaron C. , Stefanidis Dimitrios
Published: March 2021

Introduction

In 2011 and 2017, the Society for Simulation in Healthcare Research Committee convened summits to develop a forward-thinking agenda for simulation research. After the second summit, the Society for Simulation in Healthcare Research Committee sought expert opinion on the most important research questions in healthcare simulation. This study used systematic methodology to develop a prioritized research agenda for healthcare simulation.

Methods

A modified Delphi approach was conducted in 3 survey rounds. During round 1, individuals with expertise in healthcare simulation research were recruited to submit important research questions. Submitted questions were reviewed and duplicates were removed. Remaining questions were synthesized into a concise, high-level list for further rating. During round 2, these reformulated questions were distributed to the same experts who ranked their importance on a 5-point Likert scale. Average question importance ratings were calculated and shared during round 3, and a final vote was taken to identify the highest priority items.

Results

Seventeen experts submitted 74 questions, which were reduced to 21 reformulated items. Variability in expert responses decreased significantly across survey rounds, indicating that consensus had been achieved. The top 3 research question identified by the experts were related to (1) the impact of system level simulation interventions on system efficiency, patient safety, and patient outcomes; (2) the return on investment of simulation for healthcare systems, and (3) whether a dose-response relationship exists between simulation training and performance/patient outcomes.

Conclusions

The agenda developed in this study may help guide and focus researcher efforts and funding agency decisions, ultimately helping advance the field.
Rolling balance board of adjustable geometry as a tool to assess balancing skill and to estimate reaction time delay
Authors: Molnar Csenge A. , Zelei Ambrus , Insperger Tamas
Published: March 2021

The relation between balancing performance and reaction time is investigated for human subjects balancing on rolling balance board of adjustable physical parameters: adjustable rolling radius
R
and adjustable board elevation
h
. A well-defined measure of balancing performance is whether a subject can or cannot balance on balance board with a given geometry (
R
,
h
). The balancing ability is linked to the stabilizability of the underlying two-degree-of-freedom mechanical model subject to a delayed proportional–derivative feedback control. Although different sensory perceptions involve different reaction times at different hierarchical feedback loops, their effect is modelled as a single lumped reaction time delay. Stabilizability is investigated in terms of the time delay in the mechanical model: if the delay is larger than a critical value (critical delay), then no stabilizing feedback control exists. Series of balancing trials by 15 human subjects show that it is more difficult to balance on balance board configuration associated with smaller critical delay, than on balance boards associated with larger critical delay. Experiments verify the feature of the mechanical model that a change in the rolling radius
R
results in larger change in the difficulty of the task than the same change in the board elevation
h
does. The rolling balance board characterized by the two well-defined parameters
R
and
h
can therefore be a useful device to assess human balancing skill and to estimate the corresponding lumped reaction time delay.
Viruses, cancer and non-self recognition
Authors: Padariya Monikaben , Kalathiya Umesh , Mikac Sara , Dziubek Katarzyna , Tovar Fernandez Maria C. , Sroka Ewa , Fahraeus Robin , Sznarkowska Alicja
Published: March 2021

Virus–host interactions form an essential part of every aspect of life, and this review is aimed at looking at the balance between the host and persistent viruses with a focus on the immune system. The virus–host interaction is like a cat-and-mouse game and viruses have developed ingenious mechanisms to manipulate cellular pathways, most notably the major histocompatibility (MHC) class I pathway, to reside within infected cell while evading detection and destruction by the immune system. However, some of the signals sensing and responding to viral infection are derived from viruses and the fact that certain viruses can prevent the infection of others, highlights a more complex coexistence between the host and the viral microbiota. Viral immune evasion strategies also illustrate that processes whereby cells detect and present non-self genetic material to the immune system are interlinked with other cellular pathways. Immune evasion is a target also for cancer cells and a more detailed look at the interfaces between viral factors and components of the MHC class I peptide-loading complex indicates that these interfaces are also targets for cancer mutations. In terms of the immune checkpoint, however, viral and cancer strategies appear different.
Testing the multiple stressor hypothesis: chlorothalonil exposure alters transmission potential of a bumblebee pathogen but not individual host health
Authors: Calhoun Austin C. , Harrod Audrey E. , Bassingthwaite Toby A. , Sadd Ben M.
Published: March 2021

Numerous threats are putting pollinator health and essential ecosystem pollination services in jeopardy. Although individual threats are widely studied, their co-occurrence may exacerbate negative effects, as posited by the multiple stressor hypothesis. A prominent branch of this hypothesis concerns pesticide–pathogen co-exposure. A landscape analysis demonstrated a positive association between local chlorothalonil fungicide use and microsporidian pathogen (
Nosema bombi
) prevalence in declining bumblebee species (
Bombus
spp.), suggesting an interaction deserving further investigation. We tested the multiple stressor hypothesis with field-realistic chlorothalonil and
N. bombi
exposures in worker-produced
B. impatiens
microcolonies. Chlorothalonil was not avoided in preference assays, setting the stage for pesticide–pathogen co-exposure. However, contrary to the multiple stressor hypothesis, co-exposure did not affect survival. Bees showed surprising tolerance to
Nosema
infection, which was also unaffected by chlorothalonil exposure. However, previously fungicide-exposed infected bees carried more transmission-ready spores. Our use of a non-declining bumblebee and potential higher chlorothalonil exposures under some scenarios could mean stronger individual or interactive effects in certain field settings. Yet, our results alone suggest consequences of pesticide co-exposure for pathogen dynamics in host communities. This underlies the importance of considering both within- and between-host processes when addressing the multiple stressor hypothesis in relation to pathogens.
Specialized spatial cognition is associated with reduced cognitive senescence in a food-caching bird
Authors: Heinen Virginia K. , Pitera Angela M. , Sonnenberg Benjamin R. , Benedict Lauren M. , Branch Carrie L. , Bridge Eli S. , Pravosudov Vladimir V.
Published: March 2021

Senescence, the gradual reduction and loss of function as organisms age, is a widespread process that is especially pronounced in cognitive abilities. Senescence appears to have a genetic basis and can be affected by evolutionary processes. If cognitive senescence is shaped by natural selection, it may be linked with selection on cognitive abilities needed for survival and reproduction, such that species where fitness is directly related to cognitive abilities should evolve delayed cognitive senescence likely resulting in higher lifetime fitness. We used wild food-caching mountain chickadees, which rely on specialized spatial cognition to recover thousands of food caches annually, to test for cognitive senescence in spatial learning and memory and reversal spatial learning and memory abilities. We detected no signs of age-related senescence in spatial cognitive performance on either task in birds ranging from 1 to 6 years old; older birds actually performed better on spatial learning and memory tasks. Our results therefore suggest that cognitive senescence may be either delayed (potentially appearing after 6 years) or negligible in species with strong selection on cognitive abilities and that food-caching species may present a useful model to investigate mechanisms associated with cognitive senescence.
An asynchronous Mesozoic marine revolution: the Cenozoic intensification of predation on echinoids
Authors: Petsios Elizabeth , Portell Roger W. , Farrar Lyndsey , Tennakoon Shamindri , Grun Tobias B. , Kowalewski Michal , Tyler Carrie L.
Published: March 2021

Predation traces found on fossilized prey remains can be used to quantify the evolutionary history of biotic interactions. Fossil mollusc shells bearing these types of traces provided key evidence for the rise of predation during the Mesozoic marine revolution (MMR), an event thought to have reorganized global marine ecosystems. However, predation pressure on prey groups other than molluscs has not been explored adequately. Consequently, the ubiquity, tempo and synchronicity of the MMR cannot be thoroughly assessed. Here, we expand the evolutionary record of biotic interactions by compiling and analysing a new comprehensively collected database on drilling predation in Meso-Cenozoic echinoids. Trends in drilling frequency reveal an Eocene rise in drilling predation that postdated echinoid infaunalization and the rise in mollusc-targeted drilling (an iconic MMR event) by approximately 100 Myr. The temporal lag between echinoid infaunalization and the rise in drilling frequencies suggests that the Eocene upsurge in predation did not elicit a coevolutionary or escalatory response. This is consistent with rarity of fossil samples that record high frequency of drilling predation and scarcity of fossil prey recording failed predation events. These results suggest that predation intensification associated with the MMR was asynchronous across marine invertebrate taxa and represented a long and complex process that consisted of multiple uncoordinated steps probably with variable coevolutionary responses.
Fine-tuning of SUMOylation modulates drought tolerance
Authors: Li Xuewei , Zhou Shuangxi , Lu Liyuan , Dang Huan , Liu Zeyuan , Li Huimin , Chu Baohua , Chen Pengxiang , Ma Ziqing , Zhao Shuang , Nocker Steve van , Ma Fengwang , Guan Qingmei
Published: March 2021

SUMOylation is involved in various aspects of plant biology, including drought stress. However, the relationship between SUMOylation and drought stress tolerance is complex; whether SUMOylation has a crosstalk with ubiquitination in response to drought stress remains largely unclear. In this study, we found that both increased and decreased SUMOylation led to increased survival of apple (Malus×domestica) under drought stress: both transgenicMdSUMO2Aoverexpressing (OE) plants andMdSUMO2RNAi plants exhibited enhanced drought tolerance. We further confirmed that MdDREB2A is one of the MdSUMO2 targets. Both transgenicMdDREB2AOE andMdDREB2AK192ROE plants (which lacked the key site of SUMOylation by MdSUMO2A) were more drought tolerant than wild-type plants. However,MdDREB2AK192ROE plants had a much higher survival rate thanMdDREB2AOE plants. We further showed SUMOylated MdDREB2A was conjugated with ubiquitin by MdRNF4 under drought stress, thereby triggering its protein degradation. In addition,MdRNF4RNAi plants were more tolerant to drought stress. These results revealed the molecular mechanisms that underlie the relationship of SUMOylation with drought tolerance and provided evidence for the tight control of MdDREB2A accumulation under drought stress mediated by SUMOylation and ubiquitination.
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

Therapeutic 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

Energetic 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

All 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

Developing 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 summary

To 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.
What if risk factors influenced the variability of health outcomes as well as the mean? Evidence and implications
Authors: Bann David , Cole Tim J
Published: March 2021

Risk factors may affect the variability as well as the mean of health outcomes. Understanding this can aid aetiological understanding and public health translation, in that interventions which shift the outcome mean and reduce variability are preferable to those which affect only the mean. However, few statistical tools routinely test for differences in variability. We used GAMLSS (Generalised Additive Models for Location, Scale and Shape) to investigate how multiple risk factors (sex, childhood social class and midlife physical inactivity) related to differences in health outcome mean and variability. The 1970 British birth cohort study was used, with body mass index (BMI; N = 6,025) and mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; N = 7,128) as outcomes. For BMI, males had a 2% higher mean than females yet 28% lower variability. Lower social class and physical inactivity were associated with higher mean and higher variability (6% and 13% respectively). For mental wellbeing, gender was not associated with the mean while males had 4% lower variability. Lower social class and physical inactivity were associated with lower mean yet higher variability (−7% and 11% respectively). This provides empirical support for the notion that risk factors can reduce or increase variability in health outcomes. Such findings may be explained by heterogeneity in the causal effect of each exposure, by the influence of other (typically unmeasured) variables, and/or by measurement error. This underutilised approach to the analysis of continuously distributed outcomes may have broader utility in epidemiological, medical, and psychological sciences.
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

Changes 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

When 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

The 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

Host 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

The 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.

Highlight

Global (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

Birdsong 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

Objective

The 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.

Results

We 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

The 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

Seizures 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.

Teaser

We uncover the roles of excitation and inhibition during seizures, thus opening a path to more targeted therapy of epilepsy.
Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons
Authors: Yamagata Tetsushi , Ogiwara Ikuo , Tatsukawa Tetsuya , Suzuki Toshimitsu , Otsuka Yuka , Imaeda Nao , Mazaki Emi , Inoue Ikuyo , Tokonami Natsuko , Hibi Yurina , Itohara Shigeyoshi , Yamakawa Kazuhiro
Published: March 2021

Expressions of voltage-gated sodium channels Nav1.1 and Nav1.2, encoded bySCN1AandSCN2Agenes respectively, have been reported to be mutually exclusive in most brain regions. In juvenile and adult neocortex, Nav1.1 is predominantly expressed in inhibitory neurons while Nav1.2 is in excitatory neurons. Although a distinct subpopulation of layer V (L5) neocortical excitatory neurons were also reported to express Nav1.1, their nature has been uncharacterized. In hippocampus, Nav1.1 has been proposed to be expressed only in inhibitory neurons. By using newly-generated transgenic mouse lines expressingScn1apromoter-driven green fluorescent protein (GFP), here we confirm the mutually-exclusive expressions of Nav1.1 and Nav1.2 and the absence of Nav1.1 in hippocampal excitatory neurons. We also show that Nav1.1 is expressed in inhibitory and a subpopulation of excitatory neurons not only in L5 but all layers of neocortex. By using neocortical excitatory projection neuron markers including FEZF2 for L5 pyramidal tract (PT) and TBR1 for layer VI (L6) cortico-thalamic (CT) projection neurons, we further show that most L5 PT neurons and a minor subpopulation of layer II/III (L2/3) cortico-cortical (CC) neurons express Nav1.1 while the majority of L6 CT, L5/6 cortico-striatal (CS) and L2/3 CC neurons express Nav1.2. These observations now contribute to the elucidation of pathological neural circuits for diseases such as epilepsies and neurodevelopmental disorders caused bySCN1AandSCN2Amutations.
A DNA repair-independent role for alkyladenine DNA glycosylase in alkylation-induced unfolded protein response
Authors: Milano Larissa , Charlier Clara F. , Andreguetti Rafaela , Cox Thomas , Healing Eleanor , Thomé Marcos P. , Elliott Ruan M. , Samson Leona D. , Masson Jean-Yves , Lenz Guido , Henriques João Antonio P. , Nohturfft Axel , Meira Lisiane B.
Published: March 2021

Alkylating agents damage DNA and proteins and are widely used in cancer chemotherapy. While the cellular responses to alkylation-induced DNA damage have been explored, knowledge of how alkylation damage affects global cellular stress responses is still sparse. Here, we examined the effects of the alkylating agent methylmethane sulfonate (MMS) on gene expression in mouse liver taking advantage of mice deficient in alkyladenine DNA glycosylase (Aag), the enzyme that initiates the repair of alkylated DNA bases. MMS induced a robust transcriptional response in wild-type liver that included markers of the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) known to be controlled by the transcription factor XBP1, a key UPR effector. Importantly, this response is significantly reduced in theAagknockout. To investigate a potential role for AAG in alkylation-induced UPR, the expression of UPR markers after MMS treatment was interrogated in human glioblastoma cell lines expressing different AAG levels. Alkylation induced the UPR in cells expressing AAG; conversely,AAGknock-down compromised UPR induction and led to a defect in XBP1 activation plus a decrease in the expression of the ER chaperone BiP. To verify that the DNA repair activity of AAG is required for this response,AAGknockdown cells were complemented with wild-typeAagor with a mutant version of theAaggene producing a glycosylase-deficient AAG protein. As expected, the glycosylase-defective mutant Aag does not fully protectAAGknockdown cells against MMS-induced cytotoxicity. Remarkably, however, alkylation-induced XBP1 activation is fully complemented by the catalytically inactive AAG enzyme. This work establishes that, in addition to its enzymatic activity, AAG has non-canonical functions in alkylation-induced UPR that contribute to the overall cellular response to alkylation.

Significance Statement

Stress response pathways, such as the DNA damage response (DDR) and the UPR, are critical in both the etiology and treatment of cancer and other chronic diseases. Knowledge of an interplay between ER stress and genome damage repair is emerging, but evidence linking defective DNA repair and impaired ER stress response is lacking. Here, we show that AAG is necessary for UPR activation in response to alkylating agents. AAG-deficient mice and human cancer cells are impaired in alkylation-induced UPR. Strikingly, this defect can be complemented by an AAG variant defective in glycosylase activity. Our studies suggest AAG has non-canonical functions and identify AAG as a point of convergence for stress response pathways. This knowledge could be explored to improve cancer treatment.
Layer-specific stimulations of parvalbumin-positive cortical interneurons in mice entrain brain rhythms to different frequencies
Authors: David François , Borel Mélodie , Ayub Suleman , Ruther Patrick , Gentet Luc J.
Published: March 2021

Neocortical interneurons provide inhibition responsible for organizing neuronal activity into brain oscillations that subserve cognitive functions such as memory, attention or prediction. However, little is known about the interneuronal contribution to the entrainment of neocortical oscillations within and across different cortical layers. Here, using layer-specific optogenetic stimulations with micro-Light-Emitting Diode (µLED) arrays, directed toward parvalbumin-expressing (PV) interneurons in non-anesthetized awake mice, we found that supragranular layer stimulations of PV neurons were most efficient at entraining supragranular local field potential (LFP) oscillations at gamma frequencies (γ: 25 - 80 Hz), whereas infragranular layer stimulation of PV neurons better entrained the LFP at delta (δ: 2 - 5 Hz) and theta (θ: 6 - 10 Hz) frequencies.

At the level of neuronal action potential activity, we observed that supragranular neurons better followed the imposed PV stimulation rhythm than their infragranular counterparts at most frequencies when the stimulation was delivered in their respective layer. Moreover, the neuronal entrainment evoked by local stimulation could propagate across layers, though with a lesser impact when the stimulation occurs in deep layers, suggesting an orientation-selective propagation. These results establish a layer-based framework for oscillation to entrain the primary somatosensory cortex in awake conditions.
Chloridotetrakis(imidazole)copper(II) chloride. Corrigendum
Authors: Li Ting Bin , Hu Ya Li , Li Ji Kun , He Guo Fang
Published: March 2021

In the article by Li et al. [Acta Cryst. (2007), E63, m2536], four imidazole H atoms are missing in the refinement.
An architecture as a code framework to manage documentation of IT projects
Authors: Gaie Christophe , Florat Bertrand , Morvan Steven
Published: March 2021

Purpose

In the present article, the authors tackle the problem of IT documentation, which plays an important role in information technology (IT) project management.

Design/methodology/approach

They provide a simple tool based on five complementary views, which should be detailed by the project team using a classic source code management platform.

Findings

The proposed tool is open source and may be reused by any IT team in various project contexts and heterogeneous development methods.

Originality/value

This research provides an operational framework, which facilitates IT project management and documentation. The framework is open source and may be easily downloaded by any other IT team.
A systematic review of machine learning-based missing value imputation techniques
Authors: Thomas Tressy , Rajabi Enayat
Published: March 2021

Purpose

The primary aim of this study is to review the studies from different dimensions including type of methods, experimentation setup and evaluation metrics used in the novel approaches proposed for data imputation, particularly in the machine learning (ML) area. This ultimately provides an understanding about how well the proposed framework is evaluated and what type and ratio of missingness are addressed in the proposals. The review questions in this study are (1) what are the ML-based imputation methods studied and proposed during 2010–2020? (2) How the experimentation setup, characteristics of data sets and missingness are employed in these studies? (3) What metrics were used for the evaluation of imputation method?

Design/methodology/approach

The review process went through the standard identification, screening and selection process. The initial search on electronic databases for missing value imputation (MVI) based on ML algorithms returned a large number of papers totaling at 2,883. Most of the papers at this stage were not exactly an MVI technique relevant to this study. The literature reviews are first scanned in the title for relevancy, and 306 literature reviews were identified as appropriate. Upon reviewing the abstract text, 151 literature reviews that are not eligible for this study are dropped. This resulted in 155 research papers suitable for full-text review. From this, 117 papers are used in assessment of the review questions.

Findings

This study shows that clustering- and instance-based algorithms are the most proposed MVI methods. Percentage of correct prediction (PCP) and root mean square error (RMSE) are most used evaluation metrics in these studies. For experimentation, majority of the studies sourced the data sets from publicly available data set repositories. A common approach is that the complete data set is set as baseline to evaluate the effectiveness of imputation on the test data sets with artificially induced missingness. The data set size and missingness ratio varied across the experimentations, while missing datatype and mechanism are pertaining to the capability of imputation. Computational expense is a concern, and experimentation using large data sets appears to be a challenge.

Originality/value

It is understood from the review that there is no single universal solution to missing data problem. Variants of ML approaches work well with the missingness based on the characteristics of the data set. Most of the methods reviewed lack generalization with regard to applicability. Another concern related to applicability is the complexity of the formulation and implementation of the algorithm. Imputations based on k-nearest neighbors (kNN) and clustering algorithms which are simple and easy to implement make it popular across various domains.