bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding and predicting socioeconomic determinants of deforestation in Vietnam’s Central Annamites Landscape (CAL): Pilot study implementing a spatial econometric approach
Authors: Bernhard Katie P. , Zenobi Stefano , Shapiro Aurélie C.
Published: March 2021

The forests of the Greater Mekong Subregion, consisting of Myanmar, Thailand, Cambodia, Laos and Vietnam, are under high pressure from economic development and exploitation of natural resources, including but not limited to land concession, smallholder plantations and commercial agriculture, agroforestry development, mining, and road infrastructure development. While these threats are well-known, the magnitude and dynamics of their individual and interacting effects on forest cover are not fully understood. This pilot study aims to apply existing, publicly available macro, micro, and socioeconomic data in addition to remote sensing forest cover data to explore economic determinants of deforestation in the Greater Mekong, using the case of the Central Annamites Landscape (CAL) ecoregion of Vietnam. A longitudinal panel was constructed for 2000-2017, containing 1,658 observations for 144 variables across 95 Tier 2 (district) administrative units in CAL from 2000-2017 for modeling macroeconomic and socioeconomic conditions against annual tree cover loss aggregated to the Tier 2 administrative unit. The first phase of the study used tiered spatial regression analysis to correlatively identify which commodities, economic development activities, and social conditions have historically had the greatest effect on forest cover by magnitude in CAL. Based on first phase results, we selected a subset of these determinants for scenario modelling to predict possible deforestation outcomes given certain economic scenarios. The results, among others, indicate that, when spatially collocated, high poverty rates and smaller scale agricultural land conversion are key immediate determinants of deforestation. This therefore provides evidence to support programs targeting rubber, acacia harvesting, artisanal mining, and land conversion for cash crop plantations. Education is also key immediate socioeconomic factor, as poverty rate is consistently associated with tree cover loss and increased educational attainment is consistently associated with reduced tree cover loss, at approximately 12 ha per percentage increase in secondary school graduation. On the macro level, economic growth in China and Vietnam are correlatively associated with tree cover loss, as are rising trade in Myanmar and Laos. This study provides a methodological contribution to the current academic literature identifying socioeconomic dimensions of deforestation through spatial econometric analysis and scenario modelling at the landscape level. For practitioner work, this pilot provides a model or tool for strategic planning of conservation interventions in light of economic conditions and factors.
Deficiency of MicroRNA-181a Results in Transcriptome-Wide Cell Specific Changes in the Kidney that Lead to Elevated Blood Pressure and Salt Sensitivity
Authors: Paterson Madeleine R. , Jackson Kristy L. , Dona Malathi I. , Farrugia Gabriella E. , Visniauskas Bruna , Watson Anna M. D. , Johnson Chad , Prieto Minolfa C. , Evans Roger G. , Charchar Fadi , Pinto Alexander R. , Marques Francine Z. , Head Geoffrey A.
Published: March 2021

MicroRNA miR-181a is down-regulated in the kidneys of hypertensive patients and hypertensive mice.In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here we determined whether deletion of miR-181a/b-1in vivochanges BP and the molecular mechanisms involved at the single-cell level. We developed a knockout mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radio-telemetry probes were implanted in twelve-week-old C57BL/6J wild-type and miR-181a/b-1 knockout mice. Systolic and diastolic BP were 4-5mmHg higher in knockout compared with wild-type mice over 24-hours (P<0.01). Compared with wild-type mice, renal renin was higher in the juxtaglomerular cells of knockout mice. BP was similar in wild-type mice on a high (3.1%) versus low (0.3%) sodium diet (+0.4±0.8mmHg) but knockout mice showed salt sensitivity (+3.3±0.8mmHg,P<0.001). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA-sequencing in 6,699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such asStat4, Col4a1, Cd81, Flt3l, Cxcl16, Smad4. We observed up-regulation of pathways related to the immune system, inflammatory response, reactive oxygen species and nerve development, consistent with higher tyrosine hydroxylase. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension.
Phycobilisome breakdown effector NblD is required to maintain the cellular amino acid composition during nitrogen starvation
Authors: Krauspe Vanessa , Timm Stefan , Hagemann Martin , Hess Wolfgang R.
Published: March 2021

Small proteins are critically involved in the acclimation response of photosynthetic cyanobacteria to nitrogen starvation. NblD is the 66-amino-acid effector of nitrogen-limitation-induced phycobilisome breakdown, which is believed to replenish the cellular amino acid pools. To address the physiological functions of NblD, the concentrations of amino acids, intermediates of the arginine catabolism pathway and several organic acids were measured during the response to nitrogen starvation in the cyanobacteriumSynechocystissp. PCC 6803 wild type and in annblDdeletion strain. A characteristic signature of metabolite pool composition was identified, which shows that NblD-mediated phycobilisome degradation is required to maintain the cellular amino acid and organic acid pools during nitrogen starvation. Specific deviations from the wild type suggest wider-reaching effects that also affect such processes as redox homeostasis via glutathione and tetrapyrrole biosynthesis, both of which are linked to the strongly decreased glutamate pool, and transcriptional reprogramming via an enhanced concentration of 2-oxoglutarate, the metabolite co-regulator of the NtcA transcription factor. The essential role played by NblD in metabolic homeostasis is consistent with the widespread occurrence of NblD throughout the cyanobacterial radiation and the previously observed strong positive selection for thenblDgene under fluctuating nitrogen supply.

Importance

Cyanobacteria play important roles in the global carbon and nitrogen cycles. In their natural environment, these organisms are exposed to fluctuating nutrient conditions. Nitrogen starvation induces a coordinated nitrogen-saving program that includes the breakdown of nitrogen-rich photosynthetic pigments, particularly phycobiliproteins. The small protein NblD was recently identified as an effector of phycobilisome breakdown in cyanobacteria. In this study, we demonstrate that the NblD-mediated degradation of phycobiliproteins is needed to sustain cellular pools of soluble amino acids and other crucial metabolites. The essential role played by NblD in metabolic homeostasis explains why genes encoding this small protein are conserved in almost all members of cyanobacterial radiation.
Genomic Evidence of Environmental and ResidentSalmonellaSenftenberg and Montevideo Contamination in the Pistachio Supply-chain
Authors: Haendiges Julie , Davidson Gordon R. , Pettengill James B. , Reed Elizabeth , Blessington Tyann , Miller Jesse D. , Anderson Nathan , Myoda Sam , Brown Eric W. , Zheng Jie , Tikekar Rohan , Hoffmann Maria
Published: March 2021

Pistachios have been implicated in two salmonellosis outbreaks and multiple recalls in the U.S. This study performed a retrospective data analysis ofSalmonellaassociated with pistachios and a storage study to evaluate the survivability ofSalmonellaon inoculated inshell pistachios to further understand the genetics and microbiological dynamics of this commodity-pathogen pair. The retrospective data analysis on isolates associated with pistachios was performed from both short-read and long-read sequencing technologies. The sequence data were analyzed using the FDA’s Center for Food Safety and Applied Nutrition Single Nucleotide Polymorphism (SNP) analysis and Whole Genome Multi-locus Sequence Typing (wgMLST) pipeline. The storage study evaluated the survival of five strains ofSalmonellaon pistachios, both in a cocktail as well as individually. Our results demonstrate: i) evidence of persistentSalmonellaSenftenberg andSalmonellaMontevideo strains in pistachio environments, some of which may be due to clonal resident strains and some of which may be due to preharvest contamination; ii) presence of the Copper Homeostasis and Silver Resistance Island (CHASRI) inSalmonellaSenftenberg and Montevideo strains in the pistachio supply chain; and iii) different serovars ofSalmonella enterica,includingSalmonellaSenftenberg andSalmonellaMontevideo, are able to survive in pistachios over an extended period of time.

Importance

Pistachios have been linked to multistate outbreaks caused bySalmonellaserovar Senftenberg (2013, 2016) and serovar Montevideo (2016). This comprehensive study of whole-genome-sequence (WGS) data from Senftenberg and Montevideo isolates associated with pistachio outbreaks, recalls, and investigations over a nine-year period (2009-2018) was conducted to provide insights into evolutionary relationships and persistence. Multiple analytical approaches were applied including MLST, wgMLST and phylogenetic SNP analysis. The CHASRI was identified in all isolates associated with the sequence type 14 (ST14) and ST316, suggesting an adaptation in response to extrinsic pressures, such as in the farm environment. There is evidence of persistentSalmonellaSenftenberg and Montevideo strains in pistachio pre-harvest and post-harvest environments. Utilizing metagenomic sequencing during an inoculated storage study of pistachios allowed for determination of surviving serovars over an extended period of time. Defining the mechanisms of persistence of these strains is of high importance to public health.
Risk-factors Associated with Non-Vaccination in Gambian Children: A Population-Based Cohort Study
Authors: Young Benjamin , Sarwar Golam , Hossain Ilias , Mackenzie Grant
Published: March 2021

Objective

We determined the risk-factors associated with children who remain unvaccinated in rural Gambia.

Methods

We conducted prospective demographic surveillance and recorded immunisations in real-time in the Basse Health and Demographic Surveillance System. Analysis included residents born between January 1, 2012 and December 31, 2016. Demographic data included age, sex, household members and relationships, migrations, births, deaths, ethnicity, residential location, and birth type. Children were defined as unvaccinated at 10-, 15-, and 24-months of age, if they missed all primary series doses (pentavalent, oral polio and pneumococcal conjugate vaccines), secondary series (1st dose measles and yellow-fever vaccines) or both vaccination series, respectively. Multivariate three-level mixed effects logistic regressions measured the strength of association between risk-factors and being unvaccinated at age 10-, 15-, and 24-months.

Findings

38,090 infants were born during the study period, while 30,832 survived as residents and 1,567 were unvaccinated at age 10 months. Being unvaccinated at 10-months of age was associated with children not residing with their father (adjusted odds ratio [aOR] 1.38, 95% CI 1.22–1.58) or mother (aOR 2.94, 95% CI 1.33–6.46) or both parents (aOR 2.26, 1.60–3.19), whose parents were not the head of household (aOR 1.29 (1.09–1.52), experiencing external in-migration (aOR 2.78, 95% CI 1.52–5.08) and not of Mandinka ethnicity (aOR varied between 1.57 to 1.85 for three other ethnicities).

Conclusion

Unimmunised children in rural Gambia are more likely to not live with their parents and have migrated into the area. These results may inform strategies to increase vaccine coverage.
Adverse clinical outcomes in people at clinical high-risk for psychosis related to activity and glutamate function in the hippocampus
Authors: Allen Paul , Hird Emily J. , Orlov Natasza , Modinos Gemma , Bossong Matthijs , Antoniades Mathilde , Sampson Carly , Azis Matilda , Howes Oliver , Stone James , Perez Jesus , Broome Matthew , Grace Antony A. , McGuire Philip
Published: March 2021

Preclinical models suggest that psychosis involves alterations in activity and glutamate function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal-connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (ppeakFWE =.003, t=4.4, z=4.19) and a poor functional outcome (ppeakFWE <.001, t=5.52, z=4.81 and ppeakFWE <.001, t=5.25, z=4.62) were associated with a negative correlation between hippocampal activation and hippocampal Glx concentration at baseline. In addition, there was a negative association between hippocampal Glx concentration and hippocampo-striatal connectivity (ppeakFWE=.016, t=3.73, z=3.39, ppeakFWE=.014, t=3.78, z=3.42, ppeakFWE=.011, t=4.45, z=3.91, ppeakFWE=.003, t=4.92, z=4.23) in the total CHR sample, not seen in healthy volunteers. As predicted by preclinical models, adverse clinical outcomes in people at risk for psychosis are associated with altered interactions between hippocampal activity and glutamatergic function.
Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection
Authors: Smith Rebecca L. , Gibson Laura L. , Martinez Pamela P. , Ke Ruian , Mirza Agha , Conte Madison , Gallagher Nicholas , Conte Abigail , Wang Leyi , Fredrickson Rick , Edmonson Darci C. , Baughman Melinda E. , Chiu Karen K. , Choi Hannah , Jensen Tor W. , Scardina Kevin R. , Bradley Shannon , Gloss Stacy L. , Reinhart Crystal , Yedetore Jagadeesh , Owens Alyssa N. , Broach John , Barton Bruce , Lazar Peter , Henness Darcy , Young Todd , Dunnett Alastair , Robinson Matthew L. , Mostafa Heba H. , Pekosz Andrew , Manabe Yukari C. , Heetderks William J. , McManus David D. , Brooke Christopher B.
Published: March 2021

What is already known about this topic?

Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period.

What is added by this report?

We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency.

What are the implications for public health practice?

RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.
Factors Associated with Intention to Vaccinate against COVID-19 in Puerto Rico
Authors: Melin Kyle , Zhang Cheyu , Zapata Juan Pablo , Rivera Yonaira M. , Fernandez Katie , Shacham Enbal , Malavé-Rivera Souhail M. , Rodríguez-Díaz Carlos E.
Published: March 2021

COVID-19 has been particularly devastating to Black and Latinx communities in the U.S. However, data on acceptability of the COVID-19 vaccines among minority populations are limited. We conducted an online survey among adults in Puerto Rico to identify factors associated with intention to vaccinate against COVID-19. Sociodemographic variables were analyzed independently for association with intention to vaccinate. Significant associations were included in the multivariate logistic regression analysis. A total of 1016 responses were available for analysis. In the bivariate analysis, younger age, higher education, pre-covid employment, male sex, gay/bisexual identity, and single marital status were associated with increased intention to vaccinate. In the multivariate logistic regression, younger, male respondents who had higher educational attainment reported higher intention to vaccinate. Lower-income and living outside the San Juan metro region were associated with lower intention to vaccinate. National and international health organizations were identified as the most reliable sources of information, followed by healthcare professionals. These findings highlight the importance of considering sociodemographic characteristics identified with low intention to vaccinate as well as using trusted sources of information when designing public messaging related to increasing COVID-19 vaccinations.
Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine reported to EudraVigilance database
Authors: Tobaiqy Mansour , Elkout Hajer , MacLure Katie
Published: March 2021

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford-AstraZeneca vaccine amid reports of blood clot events and death of a vaccinated person, despite the European Medicines Agency and the World Health Organization assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with Oxford-AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to Pulmonary Embolism; 1 fatality to Thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events. The EMA’s Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients’ characteristics and comorbidities, may enable assessment of the causality with higher specificity.
Low levels of protective humoral immunity following mild or asymptomatic infection with SARS-CoV-2 in a community-based serological study
Authors: McDade Thomas W. , Sancilio Amelia , D’Aquila Richard , Mustanski Brian , Vaught Lauren A. , Reiser Nina L. , Velez Matthew P. , Hsieh Ryan R. , Ryan Daniel T. , Saber Rana , McNally Elizabeth M. , Demonbreun Alexis R.
Published: March 2021

The degree of protective humoral immunity after mild or asymptomatic SARS-CoV-2 infection is not known. We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding—a surrogate measure of protection against SARS-CoV-2 infection—in a large and diverse community-based seroprevalence study. Comparisons were made across three groups of seropositive participants that differed in the severity of infection and engagement with clinical care (N=790). The clinical group was seropositive for prior infection, symptomatic, and diagnosed with COVID-19 by a healthcare provider. The symptomatic group was seropositive and reported one or more symptoms of infection but received no clinical care. The asymptomatic group was seropositive but reported no symptoms. 86.2% of all infections were mild or asymptomatic; 13.8% received clinical care. Of the clinical cases, 96.3% were outpatient; only 3.7% required hospitalization. Moderate or high levels of neutralizing activity were detected following 27.5% of clinical infections, in comparison with 5.4% of symptomatic and 1.5% of asymptomatic infections. The majority of infections in the general population are mild or asymptomatic and likely result in low levels of antibody-mediated protective immunity.
Differential CTCF binding in motor neurons and lymphocytes
Authors: Arslan Belkis Atasever , Brady Scott T , Sadik Gamze Gunal
Published: March 2021

Transcriptional regulation of protein-coding genes is a primary control mechanism of cellular function. Similarities in regulation of expression for select genes between lymphocytes and neurons have led to proposals that such genes may be useful biomarkers for some neurological disorders that can be monitored via patient lymphocyte populations. Examination of shared molecular mechanisms underlying neurogenesis and lymphocyte differentiation may give help to identify relevant pathways and suggest additional biomarkers in lymphocytes that are relevant to neurological disorders. In this study, we analysed similarities and conserved regions in several genes regulated by CCCTC-binding factor (CTCF) during lymphocyte and neuronal developmental stages. We performed epigenetic analysis of CTCF binding Trak1, Gabpa, Gabpb1, Gabpb2, Gfi1, Gfi1b gene loci at T and B lymphocytes at different developmental stages, as well as in neural progenitor cells and motor neurons. Common and shared CTCF binding events at Trak1 gene suggest additional transcriptional regulatory factors that control Trak1 gene expression levels differ in neurons and lymphocytes. Gabpb1 gene includes a common CTCF binding site shared with neurons and lymphocytes. Correlation of CTCF binding analysis and gene expression profile suggests that CTCF binding plays a role in epigenetic regulation of Gabpb1 gene. In contrast, while Gfi1a gene is phylogenetically well-conserved and CTCF sites are occupied in lymphocytes, there are no CTCF binding occupied in neurons and neural progenitor cells. Low expression levels of Gfi1s in neurons indicate that regulation of this gene is CTCF-independent in neurons. Although Gfi1b is highly homologous to Gfi1, differences in expression levels suggest that Gfi1b is critical for both lymphogenesis and neurogenesis. Neurons and lymphocytes have multiple common CTCF binding sites in the Gfi1b gene, although lineage specific transcriptional regulators that play a role in their different expression levels still need to be identified. The partial overlap in CTCF regulatory sites for some genes in neurons and lymphocytes suggest that there may be markers that can exhibit parallel changes in these cells and serve as biomarkers.
Validating the automation of different measures of high temperature tolerance of small terrestrial insects
Authors: MacLean Heidi J. , Hansen Jonas Hjort , Sørensen Jesper G.
Published: March 2021

Accurately phenotyping numerous test subjects is essential for most experimental research. Collecting such data can be tedious or time-consuming, and can be biased or limited by manual observations. The thermal tolerance of small ectotherms is a good example of this type of phenotypic data, and it is widely used to investigate thermal adaptation, acclimation capacity and climate change resilience of small ectotherms. Here, we present the results of automatically generated thermal tolerance data using motion tracking on video recordings using twoDrosophilaspecies and temperature acclimation to create variation in thermal tolerances and two different heat tolerance assays. We find similar effect sizes of acclimation and hardening responses between manual and automated approaches, but different absolute tolerance estimates. This discrepancy likely reflects both technical differences and the behavioral cessation of movement rather than physiological failure measured in other assays. We conclude that both methods generate biological meaningful results, which reflect different aspects of the thermal biology, find no evidence of inflated variance in the manually scored assays, but find that automation can increase throughput without compromising quality. Further we show that the method can be applied to a wide range of arthropod taxa. We suggest that our automated method is a useful example of through-put phenotyping, and suggest this approach might be applied to other tedious laboratory traits, such as desiccation or starvation tolerance, with similar benefits to through-put. However, the interpretation and potential comparison to results using different methodology rely on thorough validation of the assay and the involved biological mechanism.
A versatile genetic toolbox forPrevotella coprienables studying polysaccharide utilization systems
Authors: Li Jing , Gálvez Eric J.C. , Amend Lena , Almasi Éva , Iljazovic Aida , Lesker Till R. , Bielecka Agata A. , Strowig Till
Published: March 2021

Prevotella copriis a prevalent inhabitant of the human gut and has been associated with plant-rich diet consumption and diverse health states. The underlying genetic basis of these associations remains enigmatic due to the lack of genetic tools. Here, we developed a novel versatile genetic toolbox for rapid and efficient genetic insertion and allelic exchange applicable toP. copristrains from multiple clades. Enabled by the genetic platform, we systematically investigated the specificity of polysaccharide utilization loci (PULs), and identified four highly conserved PULs for utilizing arabinan, pectic galactan, arabinoxylan and inulin, respectively. Further genetic and functional analysis of arabinan utilization systems illustrate thatP. coprihas evolved two distinct types of arabinan-processing PULs (PULAra) and that the type-II PULArais significantly enriched in individuals consuming a vegan diet compared to other diets. In summary, this genetic toolbox will enable functional genetic studies forP. copriin the future.
Identification and assessment of cardiolipin interactions withE. coliinner membrane proteins
Authors: Corey Robin A. , Song Wanling , Duncan Anna L. , Ansell T. Bertie , Sansom Mark S.P. , Stansfeld Phillip J.
Published: March 2021

Integral membrane proteins are localised and/or regulated by lipids present in the surrounding bilayer. Whilst bacteria such asE. colihave relatively simple membranes when compared to eukaryotic cells, there is ample evidence that many bacterial proteins bind to specific lipids, especially the anionic lipid cardiolipin. Here, we apply molecular dynamics simulations to assess lipid binding to 42 differentE. coliinner membrane proteins. Our data reveals a strong asymmetry between the membrane leaflets, with a marked increase of anionic lipid binding to the inner leaflet regions of membrane proteins, particularly for cardiolipin. From our simulations we identify over 700 independent cardiolipin binding sites, allowing us to identify the molecular basis of a prototypical cardiolipin binding site, which we validate against structures of bacterial proteins bound to cardiolipin. This allows us to construct a set of metrics for defining a high affinity cardiolipin binding site on (bacterial) membrane proteins, paving the way for a heuristic approach to defining more complex protein-lipid interactions.
Autophosphorylation of the KaiC-like protein ArlH inhibits oligomerisation and interaction with ArlI, the motor ATPase of the archaellum
Authors: de Sousa Machado J. Nuno , Vollmar Leonie , Schimpf Julia , Chaudhury Paushali , Kumariya Rashmi , van der Does Chris , Hugel Thorsten , Albers Sonja-Verena
Published: March 2021

Motile archaea are propelled by the archaellum, whose motor complex consists of the membrane protein ArlJ, the ATPase ArlI, and the ATP-binding protein ArlH. Despite its essential function and the existence of structural and biochemical data on ArlH, the role of ArlH in archaellum assembly and function remains elusive. ArlH is a structural homolog of KaiC, the central component of the cyanobacterial circadian clock. Similar to KaiC, ArlH exhibits autophosphorylation activity, which was observed for both ArlH of the euryarchaeonPyrococcus furiosus (PfArlH)and the crenarchaeonSulfolobus acidocaldarius(SaArlH). Using a combination of single molecule fluorescence measurements and biochemical assays, it is shown that autophosphorylation of ArlH is closely linked to the oligomeric state of ArlH bound to ArlI. These experiments also strongly suggest that ArlH is a hexamer in its functional ArlI bound state. Mutagenesis of the putative catalytic residue Glu-57 inSaArlH results in a reduced autophosphorylation activity and abolished archaellation and motility, suggesting that optimum phosphorylation activity of ArlH is essential for both archaellation and motility.
Medium optimization for biomass production of three peat moss (SphagnumL.) species using fractional factorial design and response surface methodology
Authors: Heck Melanie A. , Melková Ingrida , Posten Clemens , Decker Eva L. , Reski Ralf
Published: March 2021

Peat moss (Sphagnum) biomass is a promising bioresource to substitute peat in growing media with a renewable material. For sustainable production on a large scale, the productivity ofSphagnummosses has to be increased by optimizing culture conditions. Optimization was achieved using fractional factorial design and response surface methodology based on central composite design to determine concentrations of eight factors leading to highest biomass yield. We improved a standard Sphagnum medium by reducing the concentrations of NH4NO3, KH2PO4, KCl, MgSO4, Ca(NO3)2, FeSO4and a microelement solution up to 50 %. Together with a reduced sucrose concentration forSphagnum fuscum, while it remained unchanged forSphagnum palustreandSphagnum squarrosum, moss productivities were enhanced for all tested species in shake flasks. Further upscaling to 5 L photobioreactors increased the biomass yield up to nearly 50-fold forS. fuscum, 40-fold forS. palustreand 25-fold forS. squarrosumin 24 days.
Exploring an experiment-split method to estimate the generalization ability in new data: DeepKme as an example
Authors: Zou Guoyang , Li Lei
Published: March 2021

A Large number of predictors have been built based on different data sets for predicting different post-translational modification sites. However, limited to our knowledge, most of them gave an overfitting estimation of their generalization ability in new data because of the intrinsic trait—not considering the experimental sources of the new data—of the cross-validation method. Thus, we proposed and explored a new method—the experiment-split method—imitating the blinded assessment to deal with the overfitting problem in the new data. The experiment-split method logically split the training and test data based on the data’s different experimental sources, and the new data can be regarded as the data from different experimental sources. To specifically illustrate the experiment-split method, we combined an actual application, DeepKme—a predictor built by us for the lysine methylation sites, to demonstrate how it be used in the true scenarios. We compared the cross-validation method with the experiment-split method. The result suggested the experiment-split method could effectively relieve the overfitting compared with the cross-validation method and may be widely used in the field of identification participated by multiple experiments. We believe DeepKme would facilitate the related researchers’ deep thought of the experiment-split method and the overfitting phenomenon, and of course, advance the study of the lysine methylation and similar fields.
Aniridia-related Keratopathy Relevant Cell Signaling Pathways in Human Fetal Corneas
Authors: Vicente André , Sloniecka Marta , Byström Berit , Liu Jing-Xia , Domellöf Fátima Pedrosa
Published: March 2021

Background

To study aniridia-related keratopathy (ARK) relevant cell signaling pathways (Notch1, Wnt/β-catenin, Sonic hedgehog (SHH) and mTOR) in normal human fetal corneas in comparison with normal human adult corneas.

Results

20 wg fetal and normal adult corneas showed similar staining patterns for Notch1, however 10-11 wg fetal corneas showed increased presence of Notch1. Numb and Dlk1 had an enhanced presence in the fetal corneas compared to the adult corneas. Fetal corneas showed stronger immunolabeling with antibodies against β-catenin, Wnt5a and Wnt7a, Gli1, Hes1, p-rpS6, and mTOR when compared to the adult corneas. Gene expression of Notch1, Wnt5A, Wnt7A, β-catenin, Hes1, mTOR and rps6 was higher in the 9-12 wg fetal corneas when compared to adult corneas.

Conclusions

The cell signaling pathway differences found between human fetal and adult corneas were similar to those previously found in ARK corneas with the exception of Notch1. Analogous profiles of cell signaling pathway activation between human fetal corneas and ARK corneas suggests that there is a less differentiated host milieu in ARK.
Visualising formation of the ribosomal active site in mitochondria
Authors: Chandrasekaran Viswanathan , Desai Nirupa , Burton Nicholas O. , Yang Hanting , Price Jon , Miska Eric A. , Ramakrishnan V.
Published: March 2021

Ribosome assembly is an essential and complex process that is regulated at each step by specific biogenesis factors. Using cryo-electron microscopy, we identify and order major steps in the formation of the highly conserved peptidyl transferase centre (PTC) and tRNA binding sites in the large subunit of the human mitochondrial ribosome (mitoribosome). The conserved GTPase GTPBP7 regulates the folding and incorporation of core 16S ribosomal RNA (rRNA) helices and the ribosomal protein bL36m, and ensures that the PTC base U3039 has been 2′-O-methylated. Additionally, GTPBP7 binds the RNA methyltransferase NSUN4 and MTERF4, which facilitate earlier steps by sequestering H68-71 of the 16S rRNA and allowing biogenesis factors to access the maturing PTC. Consistent with the central role of NSUN4•MTERF4 and GTPBP7 during mitoribosome biogenesis,in vivomutagenesis designed to disrupt binding of theirCaenorhabditis elegansorthologs to the large subunit potently activates mitochondrial stress responses and results in severely reduced viability, developmental delays and sterility. Next-generation RNA sequencing reveals widespread gene expression changes in these mutant animals that are indicative of mitochondrial stress response activation. We also answer the long-standing question of why NSUN4 but not its enzymatic activity, is indispensable for mitochondrial protein synthesis in metazoans.
Variations in phenolic levels in grapevine buds at eco-dormancy after chemically-induced stress conditions
Authors: Daskalakis Ioannis , Stavrakaki Maritina , Sotirakoglou Kyriaki , Biniari Katerina
Published: March 2021

Viticulture is one of the briskest economic activities worldwide. A major obstacle impeding such grape yields to satisfy the demand for increased production is the insufficient period of chilling temperatures which, due to climate change, is becoming briefer. The shorter period of cold leads to poor budbreak which, in turn, results in reduced yields. To combat this issue, agronomists have resorted to treatments with chemical regulators to meet the chilling requirement for bud dormancy release several fruit-bearing plants have, including grapevines.

This study aimed at identifying and quantifying during eco-dormancy the individual polyphenolic compounds, and their possible variations, in the latent buds of the ‘Prime©’ and ‘Ralli’ table grape cultivars. The study induced chemical stress by means of four different solutions, at three discrete dates per year, for three consecutive years. Phenolics in the latent buds of the studied varieties were analyzed via HPLC. Their quantitative analysis showed variations both between the varieties and between the samples of those varieties collected after the eight treatments. The analysis indicated that the concentration of phenolics continued progressing during the annual growth cycle of the grapevine, with strong positive correlations being detected between catechin, epicatechin, chlorogenic acid, o-coumaric, piceid, procyanidins B1-B2, rutin, ε-viniferin. Luteolin registered a positive correlation with quercetin, resveratrol, o-coumaric, but not with the remaining polyphenols. The results confirmed that (a) the concentration of phenolics of the latent buds is affected by chemically-induced stress conditions, (b) depending on the date of application, significant changes appear in the variations of those phenolics.

One sentence summary

Changes in the levels of polyphenol compounds of the grapevine’s latent buds hints, for the first time, how much stress the buds actually undergo under chemically-induced stress conditions
Gene network simulations provide testable predictions for the molecular domestication syndrome
Authors: Burban Ewen , Tenaillon Maud I , Le Rouzic Arnaud
Published: March 2021

The domestication of plant species lead to repeatable morphological evolution, often referred to as thephenotypic domestication syndrome. Domestication is also associated with important genomic changes, such as the loss of genetic diversity compared to adequately large wild populations, and modifications of gene expression patterns. Here, we explored theoretically the effect of a domestication-like scenario on the evolution of gene regulatory networks. We ran population genetics simulations in which individuals were featured by their genotype (an interaction matrix encoding a gene regulatory network) and their gene expressions, representing the phenotypic level. Our domestication scenario included a population bottleneck and a selection switch mimicking human-mediated directional and canalizing selection, i.e., change in the optimal gene expression level and selection towards more stable expression across environments. We showed that domestication profoundly alters genetic architectures. Based on four examples of plant domestication scenarios, our simulations predict (i) a drop in neutral allelic diversity, (ii) a change in gene expression variance that depends upon the domestication scenario, (iii) transient maladaptive plasticity, (iv) a deep rewiring of the gene regulatory networks, with a trend towards gain of regulatory interactions, and (v) a global increase in the genetic correlations among gene expressions, with a loss of modularity in the resulting coexpression patterns and in the underlying networks. We provide empirically testable predictions on the differences of genetic architectures between wild and domesticated forms. The characterization of such systematic evolutionary changes in the genetic architecture of traits contributes to define amolecular domestication syndrome.
Alternative splicing of OAS1 alters the risk for severe COVID-19
Authors: Huffman Jennifer , Butler-Laporte Guillaume , Khan Atlas , Drivas Theodore G. , Peloso Gina M. , Nakanishi Tomoko , Verma Anurag , Kiryluk Krzysztof , Richards J. Brent , Zeberg Hugo
Published: March 2021

A locus containing OAS1/2/3 has been identified as a risk locus for severe COVID-19 among Europeans ancestry individuals, with a protective haplotype of ∼75 kilobases derived from Neanderthals. Here, we show that among several potentially causal variants at this locus, a splice variant of OAS1 occurs in people of African ancestry independently of the Neanderthal haplotype and confers protection against COVID-19 of a magnitude similar to that seen in individuals without African ancestry.
Functional neural network for decision processing, a racing network of programmable neurons with fuzzy logic where the target operating model relies on the network itself
Authors: Jumelle Frederic , So Kelvin , Deng Didan
Published: March 2021

In this paper, we are introducing a novel model of artificial intelligence, the functional neural network for modeling of human decision-making processes. This neural network is composed of multiple artificial neurons racing in the network. Each of these neurons has a similar structure programmed independently by the users and composed of an intention wheel, a motor core and a sensory core representing the user itself and racing at a specific velocity. The mathematics of the neuron’s formulation and the racing mechanism of multiple nodes in the network will be discussed, and the group decision process with fuzzy logic and the transformation of these conceptual methods into practical methods of simulation and in operations will be developed. Eventually, we will describe some possible future research directions in the fields of finance, education and medicine including the opportunity to design an intelligent learning agent with application in business operations supervision. We believe that this functional neural network has a promising potential to transform the way we can compute decision-making and lead to a new generation of neuromorphic chips for seamless human-machine interactions.
RIM-Binding Protein 2 organizes Ca2+channel topography and regulates release probability and vesicle replenishment at a fast central synapse
Authors: Butola Tanvi , Alvanos Theocharis , Hintze Anika , Koppensteiner Peter , Kleindienst David , Shigemoto Ryuichi , Wichmann Carolin , Moser Tobias
Published: March 2021

RIM-Binding Protein 2 (RIM-BP2) is a multi-domain protein of the presynaptic active zone (AZ). By binding to Rab-interacting protein (RIM), bassoon and voltage-gated Ca²⁺ channels (CaV), it is considered to be a central organizer of the topography of CaVand release sites of synaptic vesicles (SVs) at the AZ. Here, we investigated the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers with bushy cells of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked excitatory postsynaptic currents (EPSCs). Analysis of SV pool dynamics during high frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by super-resolution light and electron microscopy revealed an impaired topography of presynaptic CaVand a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in bushy cells of RIM-BP2-deficient micein vivo.

Significance Statement

RIM-binding proteins (RIM-BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmit auditory information at rates of up to hundreds of Hertz with sub-millisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of CaV2.1 Ca2+channels, and fewer docked and membrane proximal synaptic vesicles. This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization.
The criterion validity of career adapt–abilities scale with cooperation among Chinese workers
Authors: Prasad Joshua , Gardner Danielle M. , Leong Frederick T. , Zhang Jinmei , Nye Christopher D.
Published: March 2021

Purpose

This work contributes to the literature on career adaptability by examining the criterion validity of the Cooperation dimension, supporting the inclusion of cooperation into the career adaptability construct and informing the nomological network of career adaptability (Nye et al., 2018; Savickas and Porfeli, 2012). The authors also evaluate the improvements in cross-cultural generalizability argued for by Nye et al. (2018) by conducting a criterion validity study of the CAAS including cooperation using a non-Western sample.

Design/methodology/approach

Survey responses from a Chinese adult working sample (N = 208, 53.4% male) were analyzed via relative weights analysis, facilitating the comparison of the Cooperation dimension to other career adaptability dimensions and general adaptability.

Findings

Results demonstrate the added value of the Cooperation dimension across several work outcomes (i.e. work engagement, career commitment, occupational well-being, occupational stress) and highlight Cooperation in predicting interpersonal outcomes (i.e. supervisor and coworker satisfaction).

Originality/value

The inclusion of Cooperation, a dimension originally conceptualized as a career adaptability factor but only recently subjected to additional psychometric evaluation, within the career adaptability paradigm should promote both predictive validity and cross-cultural generalizability.
The perception of COVID-19 and avoidance behavior in Turkey: the role of income level, gender and education
Authors: Abdulmuhsin Amir A. , Değirmenci Bekir , Efendi̇oğlu İbrahim Halil , Durmaz Yakup
Published: March 2021

Purpose

This study aims to reveal both the effect of the perception of COVID-19 on avoidance behaviors and the mediating role of the perception of personal control in this relationship. COVID-19 emerged in December 2019 and since then, it has spread globally in a short period and has affected people socially, economically and culturally.

Design/methodology/approach

The data for the research was collected from 418 participants during COVID-19, through online questionnaires. The obtained data were analyzed through AMOS and SPSS software using structural equation modeling.

Findings

The research results show that some perceptions of COVID-19 affect avoidance behavior and that personal control has a mediating role. It has also been found that gender plays a moderating role in the relationship between COVID-19 and avoidance behavior. It has been found that women are especially more sensitive compared to men in perceiving COVID-19. This study also found that perception of COVID-19 changes depending on income.

Practical implications

After the pandemic is over, people will get in contact with each other less than before, and trade will change accordingly. People will avoid shopping in crowded places, and consumer behaviors will undergo different changes. All of these results considered, it is expected that avoidance behavior will cause some permanent behavioral changes in consumers.

Originality/value

The study answers the critical question about the effect of the perception of COVID-19 on avoidance behavior. Furthermore, the role of income level, gender and education in this relationship will be highlighted.