bluuebunny/crossref_metadata_2025 huggingface dataset:
The oldest fossil record of the extant genusBerardius(Odontoceti, Ziphiidae) from the Middle to Late Miocene boundary of the western North Pacific
Authors: Kawatani Ayako , Kohno Naoki
Published: March 2021

A new species of a beaked whale that belongs to the extant genusBerardiusis described from the Middle to Late Miocene boundary age Tsurushi Formation (ca12.3–11.5 Ma) on the Sado Island, Niigata Prefecture, Japan. The new species,Berardius kobayashiisp. nov. represents the oldest record of this genus and provides a minimum age for the emergence of this extant genus.Berardius kobayashiisp. nov. has the following generic characters: the ratio between the width of the premaxillary crests and the width of the premaxillary sac fossae is 1.0–1.25, nodular frontals make isolated protuberance on the posterior part of the vertex. Among the species within the genus,B. kobayashiisp. nov. shares a unique character withB. minimus: the apices of the left and right hamular processes of the pterygoids contact medially, forming together a posteriorly directed medial point. In addition,B. kobayashiisp. nov. displays a unique combination of the following characters: it is extremely small in size, and the nasals are short, the ratio between the length of the medial suture of nasals on the vertex and the maximum width of nasals is less than 0.4.Berardius kobayashiisp. nov. fills the gap between the origin of the genus and later diversifications of the extant species. This discovery is also key to elucidate the process of the emergence and dispersal of the genus during the Middle to Late Miocene. Based on the distributional patterns of the fossil and extant species of the genus, the western North Pacific including the Sea of Japan may have been one of the areas for the evolution and radiation of this genus at the time before 11 Ma.
Goats show higher behavioural flexibility than sheep in a spatial detour task
Authors: Raoult C. M. C. , Osthaus B. , Hildebrand A. C. G. , McElligott A. G. , Nawroth C.
Published: March 2021

The ability to adapt to changing environments is crucial for survival and has evolved based on socio-ecological factors. Goats and sheep are closely related, with similar social structures, body sizes and domestication levels, but different feeding ecologies, i.e. goats are browsers and sheep are grazers. We investigated whether goats' reliance on more patchily distributed food sources predicted an increased behavioural flexibility compared to sheep. We tested 21 goats and 28 sheep in a spatial A-not-B detour task. Subjects had to navigate around a straight barrier through a gap at its edge. After one, two, three or four of these initial A trials, the gap was moved to the opposite end and subjects performed four B trials. Behaviourally more flexible individuals should move through the new gap faster, while those less behaviourally flexible should show greater perseveration. While both species showed an accuracy reduction following the change of the gap position, goats recovered from this perseveration error from the second B trial onwards, whereas sheep did so only in the fourth B trial, indicating differences in behavioural flexibility between the species. This higher degree of flexibility in goats compared to sheep could be linked to differences in their foraging strategies.
Effect of spin labelling on the aggregation kinetics of yeast prion protein Ure2
Authors: Liu Emilie N. , Park Giovanna , Nohara Junsuke , Guo Zhefeng
Published: March 2021

Amyloid formation is involved in a wide range of neurodegenerative diseases including Alzheimer's and prion diseases. Structural understanding of the amyloid is critical to delineate the mechanism of aggregation and its pathological spreading. Site-directed spin labelling has emerged as a powerful structural tool in the studies of amyloid structures and provided structural evidence for the parallel in-register β-sheet structure for a wide range of amyloid proteins. It is generally accepted that spin labelling does not disrupt the structure of the amyloid fibrils, the end product of protein aggregation. The effect on the rate of protein aggregation, however, has not been well characterized. Here, we employed a scanning mutagenesis approach to study the effect of spin labelling on the aggregation rate of 79 spin-labelled variants of the Ure2 prion domain. The aggregation of Ure2 protein is the basis of yeast prion [URE3]. We found that all spin-labelled Ure2 mutants aggregated within the experimental timeframe of 15 to 40 h. Among the 79 spin-labelled positions, only five residue sites (N23, N27, S33, I35 and G42) showed a dramatic delay in the aggregation rate as a result of spin labelling. These positions may be important for fibril nucleation, a rate-limiting step in aggregation. Importantly, spin labelling at most of the sites had a muted effect on Ure2 aggregation kinetics, showing a general tolerance of spin labelling in protein aggregation studies.
Probability and consequences of living inside a computer simulation
Authors: Bibeau-Delisle Alexandre , Brassard FRS Gilles
Published: March 2021

It is shown that under reasonable assumptions a Drake-style equation can be obtained for the probability that our universe is the result of a deliberate simulation. Evaluating loose bounds for certain terms in the equation shows that the probability is unlikely to be as high as previously reported in the literature, especially in a scenario where the simulations are recursive. Furthermore, we investigate the possibility of eavesdropping from the outside of such a simulation and introduce a general attack that can circumvent attempts at using quantum cryptography inside the simulation, even if the quantum properties of the simulation are genuine.
A focusing and defocusing semi-discrete complex short-pulse equation and its various soliton solutions
Authors: Feng Bao-Feng , Ling Liming , Zhu Zuonong
Published: March 2021

In this paper, we are concerned with a semi-discrete complex short-pulse (sdCSP) equation of both focusing and defocusing types, which can be viewed as an analogue to the Ablowitz–Ladik lattice in the ultra-short-pulse regime. By using a generalized Darboux transformation method, various soliton solutions to this newly integrable semi-discrete equation are studied with both zero and non-zero boundary conditions. To be specific, for the focusing sdCSP equation, the multi-bright solution (zero boundary conditions), multi-breather and high-order rogue wave solutions (non-zero boundary conditions) are derived, while for the defocusing sdCSP equation with non-zero boundary conditions, the multi-dark soliton solution is constructed. We further show that, in the continuous limit, all the solutions obtained converge to the ones for its original CSP equation (Linget al. 2016Physica D327, 13–29 (doi:10.1016/j.physd.2016.03.012); Fenget al. 2016Phys. Rev. E93, 052227 (doi:10.1103/PhysRevE.93.052227)).
Socio-demographic, not environmental, risk factors explain fine-scale spatial patterns of diarrhoeal disease in Ifanadiana, rural Madagascar
Authors: Evans Michelle V. , Bonds Matthew H. , Cordier Laura F. , Drake John M. , Ihantamalala Felana , Haruna Justin , Miller Ann C. , Murdock Courtney C. , Randriamanambtsoa Marius , Raza-Fanomezanjanahary Estelle M. , Razafinjato Bénédicte R. , Garchitorena Andres C.
Published: March 2021

Precision health mapping is a technique that uses spatial relationships between socio-ecological variables and disease to map the spatial distribution of disease, particularly for diseases with strong environmental signatures, such as diarrhoeal disease (DD). While some studies use GPS-tagged location data, other precision health mapping efforts rely heavily on data collected at coarse-spatial scales and may not produce operationally relevant predictions at fine enough spatio-temporal scales to inform local health programmes. We use two fine-scale health datasets collected in a rural district of Madagascar to identify socio-ecological covariates associated with childhood DD. We constructed generalized linear mixed models including socio-demographic, climatic and landcover variables and estimated variable importance via multi-model inference. We find that socio-demographic variables, and not environmental variables, are strong predictors of the spatial distribution of disease risk at both individual and commune-level (cluster of villages) spatial scales. Climatic variables predicted strong seasonality in DD, with the highest incidence in colder, drier months, but did not explain spatial patterns. Interestingly, the occurrence of a national holiday was highly predictive of increased DD incidence, highlighting the need for including cultural factors in modelling efforts. Our findings suggest that precision health mapping efforts that do not include socio-demographic covariates may have reduced explanatory power at the local scale. More research is needed to better define the set of conditions under which the application of precision health mapping can be operationally useful to local public health professionals.
Genotype by environment interactions in coral bleaching
Authors: Drury Crawford , Lirman Diego
Published: March 2021

Climate-driven reef decline has prompted the development of next-generation coral conservation strategies, many of which hinge on the movement of adaptive variation across genetic and environmental gradients. This process is limited by our understanding of how genetic and genotypic drivers of coral bleaching will manifest in different environmental conditions. We reciprocally transplanted 10 genotypes ofAcropora cervicornisacross eight sites along a 60 km span of the Florida Reef Tract and documented significant genotype × environment interactions in bleaching response during the severe 2015 bleaching event. Performance relative to site mean was significantly different between genotypes and can be mostly explained by ensemble models of correlations with genetic markers. The high explanatory power was driven by significant enrichment of loci associated DNA repair, cell signalling and apoptosis. No genotypes performed above (or below) bleaching average at all sites, so genomic predictors can provide practitioners with ‘confidence intervals' about the chance of success in novel habitats. These data have important implications for assisted gene flow and managed relocation, and their integration with traditional active restoration.
The mass balance model perfectly fits both Hall et al. underfeeding
data and Horton et al. overfeeding data
Authors: Arencibia-Albite Francisco , Manninen Anssi H.
Published: March 2021

Background & Aims

Recently, the validity of mass balance model (MBM) was questioned based
on two feeding studies. Thus, we simulated both of these feeding
trials.

Methods

MBM describes the temporal evolution of body weight and body composition
under a wide variety of feeding experiments. This computational study
simulated, utilizing MBM, the underfeeding trial by Hall et al.
(Cell Metab. 2015;22:427-36) and the
overfeeding trial by Horton et al. (Am J Clin
Nutr. 1995;62:19-29).

Results

Our simulation results indicate that data from both of these feeding
trials perfectly match MBM-based predictions, i.e., MBM gives a remarkably
accurate description of experimental data.

Conclusions

It is becoming increasingly clear that our model (MBM) is perfectly able
to predict body weight and body composition fluctuations under a wide
variety of feeding experiments.

“There is a stupid humility that is not at all rare, and those afflicted
with it are altogether unfit to become devotees of knowledge. As soon as a
person of this type perceives something striking, he turns on his heel, as
it were, and says to himself: “You have made a mistake. What is the matter
with your senses? This cannot, may not, be the truth.” And then, instead of
looking and listening again, more carefully, he runs away from the striking
thing, as if he had been intimidated, and tries to remove it from his mind
as fast as he can. For his inner canon says: “I do not want to see anything
that contradicts the prevalent opinion. Am I called to discover new truths?
There are too many old ones, as it is…”

– Friedrich Nietzsche, The Gay Science
(1882)
Does Telemedicine Reduce health disparities? Longitudinal Evidence during the COVID-19 Pandemic in the US
Authors: Roghani Ali , Panahi Samin
Published: March 2021

Objective

The COVID-19 pandemic could be a significant health issue for the elderly population and those with pre-excising chronic condition. In response to the pandemic health care services have increased the use of telehealth medicine. The propose of this study is to examine factors associated with access to telemedicine before and after COVID-19 based on sociodemographic factors and type of chronic disease.

Method

We have used data from the Research and Development Survey (RANDS) at two different time points Data collection for the first wave occurred between June 9, 2020 and July 6, 2020 (n= 6786), second wave was between August 3, 2020 and August 20, 2020 (n=5972). Three questions have been asked from the participant: 1) did the provider offer telemedicine before the pandemic? 2) does the provider offer telemedicine during the pandemic? And 3) have the participants schedule telemedicine appointments?

Result

In both waves, 62 % of the participants reported providers did not have telemedicine services prior to the COVID-19 pandemic. However, we found a 22% increase in offering telemedicine in six first month of the COVID-19 pandemic. The finding shows almost no change in providing telemedicine between June and August. The data indicates just a 0.5% and 0.1% increase in accessing telemedicine, and scheduling in August than June, respectively. Patients older than 65 had higher access to telemedicine and had higher scheduling frequencies than other age groups, while they had the lowest access prior to the COVID-19. Blacks had the highest access to telemedicine services than other races (40%). Additionally, females, higher education, and living in metropolitan areas were associated with higher access and scheduling during the pandemic. There was a variation of access and scheduling in different chronic diseases, however, providers offered more remote services for those who diagnosed by diabetes.

Conclusion

The aim of telemedicine is to reduce disparities in healthcare access. The findings of this study show telemedicine has reduced racial disparities and provided greater accessibility for older groups. However, spatial and educational disparities are still noticeable. Research is necessary to examine how healthcare must address the socioeconomic heterogeneity in telemedicine by avoiding further disparities.
Dynamic changes in human single cell transcriptional signatures during fatal sepsis
Authors: Qiu Xinru , Li Jiang , Bonenfant Jeff , Jaroszewski Lukasz , Klein Walter , Godzik Adam , Nair Meera G.
Published: March 2021

Systemic infections, especially in patients with chronic diseases, result in sepsis: an explosive, uncoordinated immune response that can lead to multisystem organ failure with a high mortality rate. Sepsis survivors and non-survivors oftentimes have similar clinical phenotypes or sepsis biomarker expression upon diagnosis, suggesting that the dynamics of sepsis in the critical early stage may have an impact on these opposite outcomes. To investigate this, we designed a within-subject study of patients with systemic gram-negative bacterial sepsis with surviving and fatal outcomes and performed single-cell transcriptomic analyses of peripheral blood mononuclear cells (PBMC) collected during the critical period between sepsis recognition and 6 hours. We observed that the largest sepsis-induced expression changes over time in surviving versus fatal sepsis were in CD14+ monocytes, including gene signatures previously reported for sepsis outcomes. We further identify changes in the metabolic pathways of both monocytes and platelets, the emergence of erythroid precursors, and T cell exhaustion signatures, with the most extreme differences occurring between the non-sepsis control and the sepsis non-survivor. Our single-cell observations are consistent with trends from public datasets but also reveal specific effects in individual immune cell populations, which change within hours. In conclusion, this pilot study provides the first single-cell results with a repeated measures design in sepsis to analyze the temporal changes in the immune cell population behavior in surviving or fatal sepsis. These findings indicate that tracking temporal expression changes in specific cell-types could lead to more accurate predictions of sepsis outcomes. We also identify molecular pathways that could be therapeutically controlled to improve the sepsis trajectory toward better outcomes.

Summary sentence

Single cell transcriptomics of peripheral blood mononuclear cells in surviving and fatal sepsis reveal inflammatory and metabolic pathways that change within hours of sepsis recognition.
Experiences of COVID-19 Recovered Patients – A Qualitative Case Study from a Hotspot in Saudi Arabia
Authors: Alhajjaji Abdulrahman , Kurdi Ahmad , Faqeh Sultan , Alansari Safwan , Abdulaziz Akrm , Allihyani Moayad , Almaghamsi Omar , Cheema Ejaz , Ali Majid
Published: March 2021

Background

COVID-19 is highly contagious and can have fatal outcomes in the elderly and those with comorbidities. Social distancing is highly recommended by the World Health Organization to prevent the spread of the disease. However, it is difficult to maintain social distancing in highly populated areas where people live in close proximity. Such high-risk areas have the potential to become hotspots for the disease spread, should one person therein contract the disease. Nakkasah is one such area in the Makkah city of Saudi Arabia which has been a hotspot in this pandemic. This study aims to qualitatively explore the experiences of COVID-19 recovered patients residing in this area.

Methods

We employed semi-structured face-to-face interviews with people living in Nakkasah, above 18 years of age, and recovered from COVID-19. An interview guide was developed, validated, piloted, and minor changes were made. Two trained students conducted the interviews in the Arabic language in a semi-private area of the community center. The interviews were audio-recorded, with informed consent from interviewees, transcribed verbatim, and thematically analyzed later.

Results

Eleven eligible COVID-19 recovered people (two female and nine male) agreed to be interviewed, and their verbal informed consent was audio recorded. The mean interview time was 24 minutes. Thematic analysis generated 30 subthemes, which were categorized into seven overarching themes: information about COVID-19; life during COVID-19 illness; spreading of COVID-19; precautionary measures; interventions that helped in recovery; impact of COVID-19 on life; support received during COVID-19 illness.

Conclusion

Experiences of people from the hotspot who had recovered from COVID-19 highlighted how life had been like in the hotspot under lockdown especially with having been afflicted with the infection, factors that facilitated their recovery, and the way their lives were and have been affected due to COVID-19.
Anti-tRNA synthetase syndrome interstitial lung disease: A single center experience
Authors: Wilfong Erin M. , Young-Glazer Jennifer J. , Sohn Bret K. , Schroeder Gabriel , Annapureddy Narender , Gillaspie Erin A. , Barnado April , Crofford Leslie J. , Dudenhofer Rosemarie Beckford
Published: March 2021

Background

Recognition of Anti tRNA synthetase (ARS) related interstitial lung disease (ILD) is key to ensuring patients have prompt access to immunosuppressive therapies. The purpose of this retrospective cohort study was to identify factors that may delay recognition of ARS-ILD.

Methods

Patients seen at Vanderbilt University Medical Center (VUMC) between 9/17/2017-10/31/2018 were included in this observational cohort. Clinical and laboratory features were obtained via chart abstraction. Kruskal-Wallis ANOVA, Mann-Whitney U, and Fisher’s exact t tests were utilized to determine statistical significance.

Results

Patients with ARS were found to have ILD in 51.9% of cases, which was comparable to the frequency of ILD in systemic sclerosis (59.5%). The severity of FVC reduction in ARS (53.2%) was comparable to diffuse cutaneous systemic sclerosis (56.8%, p=0.48) and greater than dermatomyositis (66.9%, p=0.005) or limited cutaneous systemic sclerosis (lcSSc, 71.8%, p=0.005). Frank honeycombing was seen with ARS antibodies but not other myositis autoantibodies. ARS patients were more likely to first present to a pulmonary provider in a tertiary care setting (53.6%), likely due to fewer extrapulmonary manifestations. Only 33% of ARS-ILD were anti-nuclear antibody, rheumatoid factor, or anti-cyclic citrullinated peptide positive. Patients with ARS-ILD had a two-fold longer median time to diagnosis compared to other myositis-ILD patients (11.0 months, IQR 8.5 to 43 months vs. 5.0 months, IQR 3.0 to 9.0 months, p=0.003).

Conclusions

ARS patients without prominent extra-pulmonary manifestations are at high risk for not being recognized as having a connective tissue disease related ILD and miscategorized as UIP/IPF without comprehensive serologies.
Trends in Fentanyl and Fentanyl Derivative Utilization in the United States
Authors: Stemrich Raymond A. , Weber Jordan V. , McCall Kenneth L. , Piper Brian J.
Published: March 2021

Objective

The primary objective of this study was to explore fentanyl and fentanyl derivative distribution patterns from 2010 and 2019 across the United States (US). This study builds upon previous literature that has analyzed the trends in opioid distribution and assesses changes in opioid prescription preferences.

Methods

The amount of fentanyl base distributed in the US from 2010-2019 was obtained from the Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System (ARCOS). Fentanyl derivatives (sufentanil, alfentanil, remifentanil) were also analyzed using ARCOS from 2010-2017, the most recent date reported. Census data from the American Community Survey was used to correct for population. Prescriptions, units, and reimbursement of fentanyl and fentanyl citrate formulations for 2010 and 2019 were obtained from Medicaid and prescriber specialty in Medicare Part D.

Results

Total grams of fentanyl distributed in the US from 2010 to 2019 decreased by 63%. Correspondingly, there was a 65% decrease in the milligrams per person distributed when correcting for population. From a regional perspective, Ohio had the greatest decrease (−79.3%) while Mississippi saw the smallest (−44.5%). Medicaid reimbursement in 2019 was $165 million for over eight hundred-thousand prescriptions with the majority to generic (99.7%) and injectable (77.6%) formulations. Interventional pain management and anesthesia were over-represented, and hematology/oncology under-represented for fentanyl in Medicare.

Conclusion

The production and distribution of fentanyl-based substances has decreased, although not uniformly, in the US over the last decade. Additionally, the most prescribed formulations of fentanyl have transitioned away from transdermal, potentially in an effort to regulate its availability. Although impactful, the overdose deaths attributed to synthetic opioid deaths continue to increase highlighting the need for public health interventions beyond the pharmaceutical and medical communities.
Does the use of intraoperative CT scan improve outcomes in Orthopaedic surgery? A protocol for systematic review and meta-analysis
Authors: Kumar Vishal , Baburaj Vishnu , Patel Sandeep , Sharma Siddhartha , Vaishya Raju
Published: March 2021

Background

Intraoperative 3D imaging is a valuable tool to visualise complex anatomical structures and position implants optimally. This is an emerging technology and there is a paucity in literature of articles describing the same.

Objectives

This systematic review aims to compare the outcome of surgeries done under 3D imaging to those done under 2D fluoroscopy by analysing the evidence in literature.

Methods

A systematic review will be conducted adhering to the PRISMA guidelines. Electronic databases of PubMed, Embase and Scopus will be searched with a pre-defined search string. A manual search will also be conducted on the references of the included articles. Original research articles published in English that directly compare the outcomes of intraoperative 3D imaging with fluoroscopy will be included. Review articles, conference abstracts and animal studies will be excluded. Outcome measures will be extracted from the selected studies and analysed with the help of appropriate software.
Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization
Authors: Wang Pengfei , Casner Ryan G. , Nair Manoj S. , Wang Maple , Yu Jian , Cerutti Gabriele , Liu Lihong , Kwong Peter D. , Huang Yaoxing , Shapiro Lawrence , Ho David D.
Published: March 2021

The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been described recently. We now report that another emergent variant from Brazil, P.1, is not only refractory to multiple neutralizing monoclonal antibodies, but also more resistant to neutralization by convalescent plasma (3.4 fold) and vaccinee sera (3.8-4.8 fold). The cryo-electron microscopy structure of a soluble prefusion-stabilized spike reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position, with the functional impact of mutations appearing to arise from local changes instead of global conformational alterations. The P.1 variant threatens current antibody therapies but less so the protective efficacy of our vaccines.
The Disease-Associated ProteinsDrosophilaNab2 and Ataxin-2 Interact with Shared RNAs and Coregulate Neuronal Morphology
Authors: Rounds J. Christopher , Corgiat Edwin B. , Ye Changtian , Behnke Joseph A. , Kelly Seth M. , Corbett Anita H. , Moberg Kenneth H.
Published: March 2021

Nab2encodes a conserved polyadenosine RNA-binding protein (RBP) with broad roles in post-transcriptional regulation, including in poly(A) RNA export, poly(A) tail length control, transcription termination, and mRNA splicing. Mutation of theNab2human orthologZC3H14gives rise to an autosomal recessive intellectual disability, but understanding of Nab2/ZC3H14 function in metazoan nervous systems is limited, in part because no comprehensive identification of metazoan Nab2/ZC3H14-associated RNA transcripts has yet been conducted. Moreover, many Nab2/ZC3H14 functional protein partnerships likely remain unidentified. Here we present evidence thatDrosophila melanogasterNab2 interacts with the RBP Ataxin-2 (Atx2), a neuronal translational regulator, and implicate these proteins in coordinate regulation of neuronal morphology and adult viability. We then present the first high-throughput identifications of Nab2- and Atx2-associated RNAs inDrosophilabrain neurons using an RNA immunoprecipitation-sequencing (RIP-Seq) approach. Critically, the RNA interactomes of each RBP overlap, and Nab2 exhibits high specificity in its RNA associations in neuronsin vivo, associating with a small fraction of all polyadenylated RNAs. The identities of shared associated transcripts (e.g.drk,me31B,stai) and of transcripts specific to Nab2 or Atx2 (e.g.Arpc2,tea, respectively) promise insight into neuronal functions of and interactions between each RBP. Significantly, Nab2-associated RNAs are overrepresented for internal A-rich motifs, suggesting these sequences may partially mediate Nab2 target selection. Taken together, these data demonstrate that Nab2 opposingly regulates neuronal morphology and shares associated neuronal RNAs with Atx2, and thatDrosophilaNab2 associates with a more specific subset of polyadenylated mRNAs than its polyadenosine affinity alone may suggest.
Comparative analysis of RNA enrichment methods for preparation ofCryptococcus neoformansRNA sequencing libraries
Authors: Telzrow Calla L. , Zwack Paul J. , Righi Shannon Esher , Dietrich Fred S. , Chan Cliburn , Owzar Kouros , Alspaugh J. Andrew , Granek Joshua A.
Published: March 2021

Ribosomal RNA (rRNA) is the major RNA constituent of cells, therefore most RNA sequencing (RNA-Seq) experiments involve removal of rRNA. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper sequencing would need to be performed to balance the sequencing reads wasted on rRNA. The ideal RNA enrichment method would remove all rRNA without affecting other RNA in the sample. We have tested the performance of three RNA enrichment methods on RNA isolated fromCryptococcus neoformans, a fungal pathogen of humans. We show that the RNase H depletion method unambiguously outperforms the commonly used Poly(A) isolation method: the RNase H method more efficiently depletes rRNA while more accurately recapitulating the expression levels of other RNA observed in an unenriched “gold standard”. The RNase H depletion method is also superior to the Ribo-Zero depletion method as measured by rRNA depletion efficiency and recapitulation of protein-coding gene expression levels, while the Ribo-Zero depletion method performs moderately better in preserving non-coding RNA (ncRNA). Finally, we have leveraged this dataset to identify novel long non-coding RNA (lncRNA) genes and to accurately map theC. neoformansmitochondrial rRNA genes.

ARTICLE SUMMARY

We compare the efficacy of three different RNA enrichment methods for RNA-Seq inCryptococcus neoformans: RNase H depletion, Ribo-Zero depletion, and Poly(A) isolation. We show that the RNase H depletion method, which is evaluated inC. neoformanssamples for the first time here, is highly efficient and specific in removing rRNA. Additionally, using data generated through these analyses, we identify novel long non-coding RNA genes inC. neoformans. We conclude that RNase H depletion is an effective and reliable method for preparation ofC. neoformansRNA-Seq libraries.
redBERT: A Topic Discovery and Deep Sentiment Classification Model on COVID-19 Online Discussions Using BERT NLP Model
Authors: Pandey Chaitanya
Published: March 2021

A Natural Language Processing (NLP) method was used to uncover various issues and sentiments surrounding COVID-19 from social media and get a deeper understanding of fluctuating public opinion in situations of wide-scale panic to guide improved decision making with the help of a sentiment analyser created for the automated extraction of COVID-19 related discussions based on topic modelling. Moreover, the BERT model was used for the sentiment classification of COVID-19 Reddit comments. These findings shed light on the importance of studying trends and using computational techniques to assess human psyche in times of distress.
Ammonia-oxidizing archaea possess a wide range of cellular ammonia affinities
Authors: Jung Man-Young , Sedlacek Christopher J. , Dimitri Kits K. , Mueller Anna J. , Rhee Sung-Keun , Hink Linda , Nicol Graeme W. , Bayer Barbara , Lehtovirta-Morley Laura , Wright Chloe , de la Torre Jose R. , Herbold Craig W. , Pjevac Petra , Daims Holger , Wagner Michael
Published: March 2021

Nitrification, the oxidation of ammonia to nitrate, is an essential process in the biogeochemical nitrogen cycle. The first step of nitrification, ammonia oxidation, is performed by three, often co- occurring guilds of chemolithoautotrophs: ammonia-oxidizing bacteria (AOB), archaea (AOA), and complete ammonia oxidizers (comammox). Substrate kinetics are considered to be a major niche-differentiating factor between these guilds, but few AOA strains have been kinetically characterized. Here, the ammonia oxidation kinetic properties of 12 AOA representing all major phylogenetic lineages were determined using microrespirometry. Members of the genusNitrosocosmicushave the lowest substrate affinity of any characterized AOA, which are similar to previously determined affinities of AOB. This contrasts previous assumptions that all AOA possess much higher substrate affinities than their comammox or AOB counterparts. The substrate affinity of ammonia oxidizers correlated with their cell surface area to volume ratios. In addition, kinetic measurements across a range of pH values strongly supports the hypothesis that – like for AOB – ammonia and not ammonium is the substrate for the ammonia monooxygenase enzyme of AOA and comammox. Together, these data will facilitate predictions and interpretation of ammonia oxidizer community structures and provide a robust basis for establishing testable hypotheses on competition between AOB, AOA, and comammox.
Deriving accurate molecular indicators of protein synthesis through Raman-based sparse classification
Authors: Pavillon N. , Smith N. I.
Published: March 2021

Raman spectroscopy has the ability to retrieve molecular information from live biological samples non-invasively through optical means. Coupled with machine learning, it is possible to use the large amount of information contained in a Raman spectrum to create models that can predict the state of new samples based on statistical analysis from previous measurements. Furthermore, in case of linear models, the separation coefficients can be used to interpret which bands are contributing to the discrimination between experimental conditions, which correspond here to single-cell measurements of macrophages underin vitroimmune stimulation. We here evaluate a typical linear method using discriminant analysis and PCA, and compare it to regularized logistic regression (Lasso). We find that the use of PCA is not beneficial to the classification performance. Furthermore, the Lasso approach yields sparse separation vectors, since it suppresses spectral coefficients which do not improve classification, making interpretation easier. To further evaluate the approach, we apply the Lasso technique to a well-defined case where protein synthesis is inhibited, and show that the separating features are consistent with RNA accumulation and protein levels depletion. Surprisingly, when Raman features are selected purely in terms of their classification power (Lasso), the selected coefficients are contained in side bands, while typical strong Raman peaks are not present in the discrimination vector. We propose that this occurs because large Raman bands are representative of a wide variety of cellular molecules and are therefore less suited for accurate classification.
Non-canonical function of theSex-lethalgene controls the protogyny phenotype inDrosophila melanogaster
Authors: Seong Ki-Hyeon , Kang Siu
Published: March 2021

Many animal species exhibit sex differences in the time period prior to reaching sexual maturity. However, the underlying mechanism for such biased maturation remains poorly understood. Females of the fruit flyDrosophila melanogastereclose 4 h faster on average than males, owing to differences in the pupal period between the sexes; this characteristic is referred to as the protogyny phenotype. Here, we aimed to elucidate the mechanism underlying the protogyny phenotype in the fruit fly using our newly developedDrosophilaIndividual Activity Monitoring and Detecting System (DIAMonDS), which can continuously detect the precise timing of both pupariation and eclosion of individual flies. Via this system, following the laying of eggs, we detected the precise time points of pupariation and eclosion of a large number of individual flies simultaneously and succeeded in identifying the tiny differences in pupal duration between females and males. We first explored the role of physiological sex by establishing transgender flies via knockdown of the sex-determination gene,transformer(tra) and its co-factortra2, which retained the protogyny phenotype. In addition, disruption of dosage compensation bymale-specific lethal(msl-2) knockdown did not affect the protogyny phenotype. TheDrosophilamaster sex switch gene—Sxlpromotes female differentiation viatraand turns off male dosage compensation through the repression ofmsl-2.However, we observed that stage-specific whole-body knockdown and mutation ofSxlinduced disturbance of the protogyny phenotype. These results suggest that an additional, non-canonical function ofSxlinvolves establishing the protogyny phenotype inD. melanogaster.

Author summary

A wide variety of animals show differences in time points of sexual maturation between sexes. For example, in many mammals, including human beings, females mature faster than males. This maturation often takes several months or years, and precisely detecting the time point of maturation is challenging, because of the continuity of growth, especially in mammals. Moreover, the reason behind the difference in sexual maturation time points between sexes is not fully understood. The fruit flyDrosophila—a model organism—also shows biased maturation between the sexes, with females emerging 4 h faster than males (a characteristic known as the protogyny phenotype). To understand the mechanism underlying the protogyny phenotype, we used our newly developed system,DrosophilaIndividual Activity Monitoring and Detecting System (DIAMonDS), to detect the precise eclosion point in individual fruit flies. Surprisingly, our analysis of transgender flies obtained by knockdown and overexpression techniques indicated that a physiological gender might not be necessary requirement for protogyny and that a non-canonical novel function of the fruit fly master sex switch gene,Sxl, regulates protogyny in fruit flies.
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
Authors: Khan Shahzad S. , Sobu Yuriko , Dhekne Herschel S. , Tonelli Francesca , Berndsen Kerryn , Alessi Dario R. , Pfeffer Suzanne R.
Published: March 2021

Previously, we showed that cholinergic interneurons of the dorsal striatum lose cilia in mice harboring the Parkinson’s disease associated, kinase activating, R1441C LRRK2 mutation (Dhekne et al., 2018). Here we show that this phenotype is also seen in two mouse strains carrying the most common human G2019S LRRK2 mutation. Heterozygous loss of the PPM1H phosphatase that is specific for LRRK2-phosphorylated Rab GTPases (Berndsen et al., 2019) yields the same cilia loss phenotype, strongly supporting a connection between Rab GTPase phosphorylation and cilia loss. In addition, astrocytes throughout the striatum show a ciliation defect in LRRK2 and PPM1H-/+mutant models. Hedgehog signaling requires cilia, and loss of cilia correlates here with a loss in induction of Hedgehog signaling as monitored by in situ hybridization ofGli1transcripts. These data support a model in which LRRK2 and PPM1H mutant mice struggle to receive and respond to critical Hedgehog signals in the nigral-striatal pathway.
Death comes for us all: an interplay of habitat selection, movement, and social behavior relate to cause specific mortality among grey wolves
Authors: Turner Julie W. , Prokopenko Christina M. , Kingdon Katrien A. , Dupont Daniel L. J. , Zabihi-Seissan Sana , Wal Eric Vander
Published: March 2021

Avoiding death infects biological processes, including behavior. Habitat selection, movement, and sociality are highly flexible behaviors that influence the mortality risks and subsequent fitness of individuals. In the Anthropocene, animals are experiencing increased risks from direct human causes and increased spread of infectious diseases. Using integrated step selection analysis, we tested how the habitat selection, movement, and social behaviors of grey wolves vary as an individual dies due to humans or canine distemper virus (CDV) and how those behaviors may vary in the lead up to death. Behaviors that changed prior to death were strongly related to how an animal eventually died. Wolves killed by humans moved slower than wolves that survived and selected to be nearer roads closer in time to their death. Wolves that died due to CDV moved progressively slower as they neared death and reduced their avoidance of wet habitats. All animals, regardless of dying or not maintained strong selection to be near packmates across time, which seemingly contributed to disease dynamics in the packs that became infected with CDV. Habitat selection, movement, and sociality interact to put individuals and groups at greater risks, influencing their cause-specific mortality.

Lay Summary

Not much is known about behaviors prior to death in wild animals. Grey wolves killed by humans selected to be in riskier areas increasingly prior to their deaths. Wolves that died due to disease moved slower and changed their habitat selection to be in areas with more water as they became sicker. Sick wolves also continued to select for packmates, increasing the chances that the whole pack would succumb to the disease.
A pro-endocrine pancreatic transcriptional program established during development is retained in human gallbladder epithelial cells
Authors: Joglekar Mugdha V. , Sahu Subhshri , Wong Wilson KM , Satoor Sarang N. , Dong Charlotte X. , Farr Ryan J , Williams Michael D. , Pandya Prapti , Jhala Gaurang , Yang Sundy N.Y. , Vee Chew Yi , Hetherington Nicola , Thiruchevlam Dhan , Mitnala Sasikala , Rao Guduru V , Nageshwar Reddy Duvvuru , Loudovaris Thomas , Hawthorne Wayne J. , Elefanty Andrew G. , Joglekar Vinay M. , Stanley Edouard G. , Martin David , Thomas Helen E. , Tosh David , Dalgaard Louise T. , Hardikar Anandwardhan A.
Published: March 2021

Objective

Pancreatic islet β-cells are factories for insulin production; however ectopic expression of insulin is also well recognized. The gallbladder is a next-door neighbour to the developing pancreas. Here, we wanted to understand if gallbladders contain functional insulin-producing cells.

Design

We compared developing and adult mouse as well as human gallbladder epithelial cells and islets using immunohistochemistry, flow cytometry, ELISAs, RNA-sequencing, real-time PCR, chromatin immunoprecipitation and functional studies.

Results

We demonstrate that the epithelial lining of developing, as well as adult mouse and human gallbladders naturally contain interspersed cells that retain the capacity to actively transcribe, translate, package, and release insulin. We show for the first time that human gallbladders also contain functional insulin-secreting cells with the potential to naturally respond to glucosein vitroandin situ. Notably, in a NOD mouse model of type 1 diabetes, we observed that insulin-producing cells in the gallbladder are not targeted by autoimmune cells. Conclusion: In summary, our biochemical, transcriptomic, and functional data in human gallbladder epithelial cells collectively demonstrate their potential for insulin-production under pathophysiological conditions, and open newer areas for type 1 diabetes research and therapy.

Significance of the study

What is already known about this subject?

Developing pancreas and gallbladder are next-door neighbours and share similar developmental pathways.

Human Gallbladder-derived progenitor cells were shown to differentiate into insulin-producing cells.

What are the new findings?

Gallbladder epithelium contains interspersed cells that can transcribe, translate, package and secrete insulin.

Insulin-producing cells in the gallbladder are not destroyed by immune cells in an animal model of type 1 diabetes (T1D).

Our studies demonstrating the absence of insulin splice variants in human gallbladder cells, and higher splice forms in human islets, suggest a potential mechanism (via defective ribosomal products) in escaping islet autoimmunity.

How might it impact clinical practice?

Deciphering mechanisms of protection of insulin-producing cells from immune cells in the gallbladder could help in developing strategies to prevent islet autoimmunity in T1D.
DATAD: a Python-based X-ray diffraction simulation code for arbitrary texture and arbitrary deformation
Authors: Huang J. W. , Zhang Y. Y. , Hu S. C. , Cai Y. , Luo S. N.
Published: March 2021

DATAD, a Python-based X-ray diffraction simulation code, has been developed for simulating one- and two-dimensional diffraction patterns of a polycrystalline specimen with an arbitrary texture under an arbitrary deformation state and an arbitrary detection geometry. Pixelated planar and cylindrical detectors can be used. The basic principles and key components of the code are presented along with the usage of DATAD. As validation and application cases, X-ray diffraction patterns of single-crystal and polycrystalline specimens with or without texture, or applied strain, on a planar or cylindrical detector are simulated.
What do customers want? The impact of pricing tactic persuasion knowledge and frequency of exposure
Authors: Chen Yen-Ting , Lan Li-Chi , Fang Wen-Chang
Published: March 2021

Purpose

Previous research has shown that consumers prefer a bonus pack to a price discount for virtue foods, whereas they prefer a price discount to a bonus pack for vice foods. Acting as a guilt-mitigating mechanism, a price discount justifies consumers' purchasing behavior, allowing them to save money and consume less vice foods. However, for virtue foods, neither the anticipated post-consumption guilt nor the resulting need for justification lead consumers to prefer a bonus pack to a price discount. This study investigates whether product promotions remain effective with other moderating variables.

Design/methodology/approach

The authors use pricing tactic persuasion knowledge (PTPK), which refers to the consumer persuasion knowledge of marketers' pricing tactics, as a lens to understand whether the power of these promotions could be enhanced or mitigated. The authors inferred that increasing the frequency of exposure to these foods could positively influence consumers' purchasing choices. They conducted three studies to examine these effects. In Study 1, using pearl milk tea (vice food) and sugar-free tea (virtue food), the authors contended that consumers would prefer a price discount when purchasing pearl milk tea, but a bonus pack when purchasing sugar-free tea. In Studies 2 and 3, the authors varied the participants' frequency of exposure to photographs of people in everyday situations with vice (virtue) foods.

Findings

In Study 1, PTPK was shown to be more predictive of consumer choices regarding price discounts and bonus packs. In Studies 2 and 3, the authors contended that increased exposure to vice (virtue) foods increases the selection of vice (virtue) foods by participants who were unaware of having been exposed to vice (virtue) foods.

Originality/value

This research has not only made quite managerial and policy implications for marketing but also brought the theoretical contributions for marketing researches. This research demonstrates that either for vice foods or virtue foods, a price discount is preferred to a bonus pack.