bluuebunny/crossref_metadata_2025 huggingface dataset:
Pain-related behavior is associated with increased joint innervation, ipsilateral dorsal horn gliosis, and dorsal root ganglia activating transcription factor 3 expression in a rat ankle joint model of osteoarthritis
Authors: Bourassa Valerie , Deamond Haley , Yousefpour Noosha , Fitzcharles Mary-Ann , Ribeiro-da-Silva Alfredo
Published: March 2021

Introduction:

Osteoarthritis (OA)-associated pain is often poorly managed, as our understanding of the underlying pain mechanisms remains limited. The known variability from patient to patient in pain control could be a consequence of a neuropathic component in OA.

Methods:

We used a rat monoiodoacetate model of the ankle joint to study the time-course of the development of pain-related behavior and pathological changes in the joint, dorsal root ganglia (DRG), and spinal cord, and to investigate drug treatments effects.

Results:

Mechanical hypersensitivity and loss of mobility (as assessed by treadmill) were detected from 4 weeks after monoiodoacetate. Cold allodynia was detected from 5 weeks. Using histology and x-ray microtomography, we confirmed significant cartilage and bone degeneration at 5 and 10 weeks. We detected increased nociceptive peptidergic and sympathetic fiber innervation in the subchondral bone and synovium at 5 and 10 weeks. Sympathetic blockade at 5 weeks reduced pain-related behavior. At 5 weeks, we observed, ipsilaterally only, DRG neurons expressing anti-activating transcription factor 3, a neuronal stress marker. In the spinal cord, there was microgliosis at 5 and 10 weeks, and astrocytosis at 10 weeks only. Inhibition of glia at 5 weeks with minocycline and fluorocitrate alleviated mechanical allodynia.

Conclusion:

Besides a detailed time-course of pathology in this OA model, we show evidence of contributions of the sympathetic nervous system and dorsal horn glia to pain mechanisms. In addition, late activating transcription factor 3 expression in the DRG that coincides with these changes provides evidence in support of a neuropathic component in OA pain.
Micro-mechanical fracture dynamics and damage modelling in brittle materials
Authors: Gomez Q. , Ionescu I. R.
Published: March 2021

This study explores the interplay between wave propagation and damage in brittle materials. The damage models, based on micro-mechanical fracture dynamics, capture any possible unstable growth of micro-cracks, introducing a macroscopic loss of stability. After stating the non-dimensional mathematical problem describing the wave propagation with damage, we introduce a non-dimensional number, called the microscopic evolution index, which links the micro and macro scales and discriminates the microscopic scale behaviour. For large values of microscopic evolution index, corresponding to a microscopic quasi-static process coupled with a macroscopic dynamic one, the macroscopic dynamic system could lose its hyperbolicity or become very stiff and generate shock waves. A semi-analytical solution to the one-dimensional wave propagation problem with damage, which could be very useful in the accuracy evaluation of the numerical schemes, was constructed. Concerning the asymptotic behaviour of the dynamic exact solution on the microscopic evolution index (or on the strain rate), an important strain rate sensitivity was found: the pulse loses its amplitude for decreasing strain rate and, starting with a critical value, the micro-scale model is rate independent. A possible regularization technique to smooth the shock waves at low and moderate strain rates is discussed. Finally, some numerical results analyse the role played by the the friction on the micro-cracks in the damage modelling of blast wave propagation.

This article is part of the theme issue ‘Fracture dynamics of solid materials: from particles to the globe’.
Thermal jet drilling of granite rock: a numerical 3D finite-element study
Authors: Saksala Timo , Kouhia Reijo , Mardoukhi Ahmad , Hokka Mikko
Published: March 2021

This paper presents a numerical study on thermal jet drilling of granite rock that is based on a thermal spallation phenomenon. For this end, a numerical method based on finite elements and a damage–viscoplasticity model are developed for solving the underlying coupled thermo-mechanical problem. An explicit time-stepping scheme is applied in solving the global problem, which in the present case is amenable to extreme mass scaling. Rock heterogeneity is accounted for as random clusters of finite elements representing rock constituent minerals. The numerical approach is validated based on experiments on thermal shock weakening effect of granite in a dynamic Brazilian disc test. The validated model is applied in three-dimensional simulations of thermal jet drilling with a short duration (0.2 s) and high intensity (approx. 3 MW m−2) thermal flux. The present numerical approach predicts the spalling as highly (tensile) damaged rock. Finally, it was shown that thermal drilling exploiting heating-forced cooling cycles is a viable method when drilling in hot rock mass.

This article is part of the theme issue ‘Fracture dynamics of solid materials: from particles to the globe’.
Improvement in the manufacturing process and quality of jujube vinegar in the ancient literature 『Sangayorok』
Authors: Park Hyeon-Ju , Jeon Seong Hyun , Kim So-Young , Yeo Soo-Hwan , Gwon Hee-Min
Published: March 2021

Jujube vinegar is produced using a method described in the ancient literature titled “Sangayorok”. In this vinegar production method, alcohol and acetic acid fermentation occur at the same time. This study was conducted to reproduce the traditional jujube vinegar and improve its quality. The manufacturing proess was divided into two stages of fermentation. Jujube wine was prepared using the base liquor (Mit-sool), and jujube vinegar was prepared by seed vinegar. Moreover, the optimum conditions were determined by analyzing the quality of the fermented jujube vinegar at different temperatures (20, 30, and 35°C) and initial pH conditions (pH 3, 4, and 5). We evaluated the pH, acidity, organic acid content, and antioxidant activity of the fermented jujube vinegar, and its taste was analyzed using an electronic tongue. On the 14th day of fermentation under pH 4 and at 20°C, the pH level dropped to 3.4, and the acidity was 10.4%. The total organic acid content was 6,568 mg /100 mL, of which acetic acid content was as high as 83% (5,475 mg/100 mL). Umami and sourness of the vinegar increased as the fermentation progressed. Analysis of antioxidant activity of the vinegar fermented at pH 4 and 20°C revealed that the ABTS radical scavenging activity of the jujube vinegar was 90.9%, and the total polyphenol content was 1,131.3 mg (GAE)/100 mL. These findings can form a basis for selecting optimal fermentation conditions and developing manufacturing technologies through modernized process improvements for commercialization of traditional jujube vinegar.
Effects of edible coatings with various natural browning inhibitors
on the qualitative characteristics of banana (Musa
acuminata Cavendish Subgroup) during storage
Authors: Kim Jiyoon , Choi Ji-Young , Kim Jungsoo , Moon Kwang-Deog
Published: March 2021

Bananas (Musa acuminata Cavendish Subgroup) have a short
shelf-life due to surface browning. This study aimed to select the best edible
coating agent including a natural browning inhibitor (green tea, Rhus chinensis,
rice bran and Morus alba root extracts) that can extend the shelf-life of
bananas. Bananas were coated with 1.5% carboxymethyl cellulose and 2.0% Tween 80
(CM), CM and 1.5% green tea extract, CM and 1.5% Rhus chinensis extract, CM and
rice bran extract, and CM and 1.5% Morus alba extract (CM-M). An uncoated sample
was used as the control. The weight loss, firmness, polyphenol oxidase (PPO)
activity, browning index (BI), total chlorophyll content, and color of the
coated bananas during storage were evaluated. Treatment with CM-M exhibited
lesser changes in the weight and firmness of bananas during storage, compared
with the other treatments. Moreover, CM-M delayed the enzymatic browning of
bananas during storage, maintained the PPO activity, and showed the lowest BI,
compared with other treatments. The changes in the total chlorophyll content and
color (ΔE value) were lower in the CM-M coated samples than in the
control samples. The CM-M coated samples showed decreases in the total
chlorophyll content and ΔE value compared with that noted in bananas with
the other coatings. Therefore, our findings indicated Morus alba root extract
supplementation to be the most suitable edible coating agent, which maintains
the quality and appearance of bananas during storage.
Quality characteristics of bread prepared with pregelatinized rice
flours of various cultivars
Authors: Choi Ok Ja , Jung Hee Nam
Published: March 2021

This study investigated and compared the effect of pregelatinized rice flours on
bread quality. Rice cultivars (‘Hiami’, ‘Hopyeng’,
and ‘Hyunpum’) were pregelatinized at 121°C for 15 min in
an autoclave. In the pregelatinized rice flour group, the volume and specific
volume of bread increased, along with the dough moisture, which was
significantly higher for the ‘Hiami’ and ‘Hyunpum’
flours than for the ‘Hopyeng’ flour. In the pregelatinized rice
flour group, the b value of bread crumb and crust decreased as the dough
moisture content. With respect to texture properties, the bread in the
pregelatinized rice flour group showed decreased hardness and chewiness and
inceased springiness and cohesiveness compared to raw rice flour, and the
improvement in texture properties was higher for ‘Hiami’ and
‘Hyunpum’ flours than for the ‘Hopyeng’ flour. With
respect to hardness change during storage, the retrogradation was delayed in the
pregelatinized rice flour group with increased dough moisture content, and time
constant (1/k) was higher for the ‘Hiami’ and
‘Hyunpum’ flours than for the ‘Hopyeng’ flour. The
results of this study indicate that pregelatinized rice flour, especially that
of ‘Hiami’ and ‘Hyunpum’, improves bread quality and
can be applied in the bakery industry.
Comprehensive changes of nutritional
constituents and antioxidant activities of ginseng
sprouts according to the roasting
process
Authors: Kim Su Cheol , Kang Young Min , Seong Jin A , Lee Hee Yul , Cho Du Yong , Joo Ok Soo , Lee Jin Hwan , Cho Kye Man
Published: March 2021

This study comprehensively investigated the physicochemical
properties, nutritional constituents, and antioxidant
activity of ginseng sprouts (GS) according to the roasting
process. The fatty acid and mineral contents of GS were
almost unchanged, but the free amino acid contents
decreased. Moreover, ginsenoside contents decreased during
the roasting process, whereas total phenolics and
flavonoids, Maillard reaction products, phenolic acid and
flavonol contents increased. In particular, the contents of
ginsenoside Re, Rb1, and Rd decreased by
41%/18%, 32%/30%, and
13%/23% (above/below ground), respectively,
during roasting. In contrast, the values of Rg3, compound K,
chlorogenic acid, epigallocatechin, and quercetin increased
by 167%/229%, 287%/196%,
190%/231%, 370%/229%, and
250%/387% (above/below ground), respectively.
Finally, the antioxidant effects of DPPH and ABTS, the
hydroxyl radical scavenging activity and the ferric
reducing/antioxidant power of GS increased during the
roasting process.
Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality
Authors: Loftfield Erikka , Stepien Magdalena , Viallon Vivian , Trijsburg Laura , Rothwell Joseph , Robinot Nivonirina , Biessy Carine , Bergdahl Ingvar A. , Bodén Stina , Schulze Matthias B. , Bergman Manuela , Weiderpass Elisabete , Schmidt Julie A. , Zamora-Ros Raul , Nøst Therese H. , Sandanger Torkjel M , Sonestedt Emily , Ohlsson Bodil , Katzke Verena , Kaaks Rudolf , Ricceri Fulvio , Tjønneland Anne , Dahm Christina C. , Sánchez Maria-Jose , Trichopoulou Antonia , Tumino Rosario , Chirlaque María-Dolores , Masala Giovanna , Ardanaz Eva , Vermeulen Roel , Brennan Paul , Albanes Demetrius , Weinstein Stephanie J. , Scalbert Augustin , Freedman Neal D. , Gunter Marc J. , Jenab Mazda , Sinha Rashmi , Keski-Rahkonen Pekka , Ferrari Pietro
Published: March 2021

Background

Alcohol is an established risk factor for several cancers, but modest alcohol-cancer associations may be missed due to measurement error in self-reported assessments. The identification of biomarkers of habitual alcohol intake may enhance evidence on the role of alcohol in cancer onset.

Methods

Untargeted metabolomics was used to identify metabolites correlated with habitual alcohol intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition (EPIC; n=454). Significant correlations were replicated in independent datasets of controls from case-control studies nested within EPIC (n=281) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC; n=438) study. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals for associations of alcohol-associated metabolites and self-reported alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer, and liver disease mortality in the contributing studies.

Results

Two metabolites displayed a dose-response association with alcohol intake: 2-hydroxy-3-methylbutyric acid and an unidentified compound (m/z(+):231.0839). A 1-SD increase in log2-transformed levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR=2.14; 1.39-3.31) and pancreatic cancer (OR=1.65; 1.17-2.32) in EPIC and liver cancer (OR=2.00; 1.44-2.77) and liver disease mortality (OR=2.16; 1.63-2.86) in ATBC. Conversely, a 1-SD increase in log2-transformed questionnaire-derived alcohol intake was not associated with HCC or pancreatic cancer in EPIC or liver cancer in ATBC but was associated with liver disease mortality (OR=2.19; 1.60-2.98) in ATBC.

Conclusions

2-Hydroxy-3-methylbutyric acid is a candidate biomarker of habitual alcohol intake that may advance the study of alcohol and cancer risk in population-based studies.
A meta-analysis of single visit pollination effectiveness
Authors: Page M.L. , Nicholson C.C. , Brennan R.M. , Britzman A.T. , Greer J. , Hemberger J. , Kahl H. , Müller U. , Peng Y. , Rosenberger N.M. , Stuligross C. , Wang L. , Yang L.H. , Williams N.M.
Published: March 2021

Many animals provide essential ecosystem services in the form of plant pollination. A rich literature documents considerable variation in the single visit pollination effectiveness of different plant visitors, but this literature has yet to be comprehensively synthesized. We conducted a hierarchical meta-analysis of 193 studies and extracted 1716 single visit effectiveness (SVE) comparisons for 252 plant species. We paired SVE data with visitation frequency data for 75 of these studies. Given the global dominance of honeybees in pollinator communities, we used these data to ask: 1) Do honeybees (Apis mellifera) and other floral visitors vary in their SVE?; 2) To what extent do plant and pollinator attributes predict the difference in SVE between honeybees and other visitors?; and 3) Is there a correlation between floral visitation frequency and SVE? We found that honeybees were significantly less effective than the most effective non-honeybee pollinator. Although not significantly different, honeybees also tended to be less effective than the mean community effectiveness. Honeybees were less effective as pollinators of crop plants and when compared to birds and other bees. Visitation frequency and pollination effectiveness were positively correlated, but this trend was largely driven by data from communities where honeybees were absent, suggesting that honeybees generally combine high visitation frequency and lower SVE. Our study demonstrates that non-honeybee floral visitors are highly effective pollinators of many crop and non-crop plants. While the high visitation frequency typically displayed by honeybees undoubtably makes them important pollinators, we show that honeybees are slightly less effective than the average pollinator and rarely the most effective pollinator of the plants they visit. As such, honeybees may be imperfect substitutes for the loss of wild pollinators and safeguarding global crop production will benefit from conservation of non-honeybee taxa.

Open Research Statement:

Although we are fully committed to data transparency, we are also aware of different research teams working on related meta-analyses. As such, we prefer to wait until our paper is accepted to make data publicly available but are happy to share data upon request. Data will be permanently archived on Figshare following acceptance.
Embryo Lethality Assay for Evaluating Virulence of Isolates from Bacterial Chondronecrosis with Osteomyelitis in Broilers
Authors: Ekesi Nnamdi S. , Hasan Amer , Parveen Alia , Shwani Abdulkarim , Rhoads Douglas D.
Published: March 2021

We used an embryo lethality assay (ELA) to assess virulence for different isolates from cases of bacterial chondronecrosis with osteomyelitis (BCO) in broilers. ELA has been used to measure virulence and lethal dosage of Enterococcus faecalis and Enterococcus cecorum. We hypothesized that ELA could substitute for more laborious and costly assessments of BCO isolate pathogenicity using live birds. We evaluated two different levels of bacteria injected into eggs from layer and commercial broiler embryos. Significant findings include a) Escherichia coli from neighboring farms operated by the same integrator had very different embryo lethality, b) isolate Staphylococcus agnetis 908 had low virulence in ELA, even though this isolate can induce more than 50% BCO lameness, c) Enterococcus cecorum 1415 also had low pathogenicity; even though it was recovered from severe bilateral tibial dyschondroplasia, d) human and chicken isolates of S. aureus had significant pathogenicity, e) virulence for some isolates was highly variable possibly corresponding with quality of the embryos/fertile eggs used, and f) ELA pathogenicity was much lower for our BCO isolates than previous reports which may reflect maternal environment. Overall, ELA virulence and BCO virulence are not always concordant indicating that that ELA may not be an effective measure for assessing virulence with respect to BCO.

Importance

Lameness is among the most significant animal welfare issues in the poultry industry. Bacterial infections are a major cause of lameness and different bacterial species have been obtained from lame broilers. Reliable lab-based assays are required to assess relative virulence of bacteria obtained from lame broilers. Embryo Lethality Assays have been used to compare virulence. Our results suggest that this assay may not be an effective measure of virulence related to lameness.
Impact of School Reopening on Pandemic Spread: A Case Study using an Agent-Based Model for COVID-19
Authors: Tatapudi Hanisha , Das Tapas K.
Published: March 2021

This article examines the impact of partial/full reopening of school/college campuses on the spread of a pandemic using COVID-19 as a case study. The study uses an agent-based simulation model that replicates community spread in an urban region of U.S.A. via daily social mixing of susceptible and infected individuals. Data representing population demographics, SARS-CoV-2 epidemiology, and social interventions guides the model’s behavior, which is calibrated and validated using data reported by the government. The model indicates a modest but significant increase (8.15 %) in the total number of reported cases in the region for a complete (100%) reopening compared to keeping schools and colleges fully virtual. For partial returns of 75% and 50%, the percent increases in the number of reported cases are shown to be small (2.87% and 1.26%, respectively) and statistically insignificant. The AB model also predicts that relaxing the stringency of the school safety protocol for sanitizing, use of mask, social distancing, testing, and quarantining and thus allowing the school transmission coefficient to double may result in a small increase in the number of reported infected cases (2.14%). Hence for pandemic outbreaks from viruses with similar characteristics as for SARS-CoV-2, keeping the schools and colleges open with a modest campus safety protocol and in-person attendance below a certain threshold may be advisable.
SYSTEMATIC OBSERVATION OF COVID-19 MITIGATION (SOCOM): ASSESSING FACE COVERING AND DISTANCING IN SCHOOLS
Authors: Camplain Ricky , Lopez Nanette V. , Cooper Dan M. , McKenzie Thomas , Zheng Kai , Radom-Aizik Shlomit
Published: March 2021

Introduction: During the COVID-19 pandemic, some K-12 schools resumed in-person classes with varying degrees of mitigation plans in the fall of 2020. Physical distancing and face coverings can minimize SARS-CoV-2 spread, the virus that causes COVID-19. However, no research has focused on mitigation strategy adherence during school days. Thus, we sought to develop a systematic observation protocol to capture COVID-19 mitigation strategy adherence in school environments: The Systematic Observation of COVID-19 Mitigation (SOCOM).
Methods: We extended previously validated and internationally used tools to develop the SOCOM training and implementation protocol to assess physical distancing and face covering behaviors. SOCOM was tested in diverse indoor and outdoor settings (classrooms, lunchrooms, physical education [PE], and recess) among diverse schools (elementary, secondary, and special needs).
Results: For the unique metrics of physical-distancing and face-covering behaviors, areas with more activity and a maximum of 10-15 students were ideal for accurately capturing data. Overall proportion of agreement was high for physical distancing (90.9%), face covering (88.6%), activity type (89.2%), and physical activity level (87.9%). Agreement was lowest during active recess, PE, and observation areas with ≥20 students.
Conclusions: Millions of children throughout the US are likely to return to school in the months ahead despite the current surge of COVID-19 cases. SOCOM is a relatively inexpensive tool that can be implemented by schools to determine mitigation strategy adherence and assess changes to protocols to help students return to school safely and slow the spread of COVID-19 and can be used for research purposes.
Hepatitis B infection is causally associated with extrahepatic cancers: a Mendelian randomization study
Authors: Kamiza Abram Bunya , Fatumo Segun , Singini Mwiza Gideon , Yeh Chih-Ching , Chikowore Tinashe
Published: March 2021

Overwhelming evidence suggests that chronic hepatitis infection is associated with extrahepatic cancers. However, uncertainties exist about this association as much of the current evidence evolve from observational studies which are susceptible to confounding. We performed two-sample Mendelian randomization (MR) to explore the causal associations between chronic hepatitis infection and extrahepatic cancers. Genetic variants associated with chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV) infection were identified from a large genome-wide association study. Summary level data for cancer of the biliary tract, cervix, colorectum, endometrium, esophagus, gastric, liver, lung, ovary and pancreas were obtained from the Biobank Japan. Using the inverse variance weighted method, we found chronic HBV infection to be causally associated with gastric cancer (odds ratio [OR] = 1.19 and 95% confidence interval [CI] = 1.13-1.25, P-value = 0.001) and lung cancer (OR = 1.21, 95% CI = 1.14-1.28, P-value = 0.001). Moreover, chronic HBV infection (OR = 1.34, 95% CI = 1.17-1.53, P-value = 0.007) and chronic HCV infection (OR = 2.75, 95% CI = 2.21-3.42, P-value = 0.0008) were all causally associated with liver cancer, supporting a well-established association between chronic hepatitis infection and liver cancer. In conclusions, our MR findings revealed that chronic HBV infection is causally associated with extrahepatic cancers including gastric and lung cancers.
Hydroxyl-radical scavenging activity of hydrogen does not significantly contribute to its biological function
Authors: Li Qinjian , Xie Fei , Yi Yang , Zhao Pengxiang , Zhang Xin , Zhang Xiaokang , Zhang Xujuan , Ma Xuemei
Published: March 2021

Since Ohsawa et al. reported a biological antioxidant function of hydrogen in 2007, researchers have now shown it to exert protective effects in a wide range of human and animal disease models. Clinical observations and scientific arguments suggest that a selective scavenging property of H2cannot adequately explain the beneficial effects of hydrogen. However, there is no experiment challenging the original published data, which suggested that molecular hydrogen dissolved in solution reacts with hydroxyl radicals in cell-free systems. Here we report that a hydrogen-saturated solution (0.6 mM) did not significantly reduce hydroxyl radicals in the Fenton system using 1 mM H2O2. We replicated the same condition as Ohsawa’s study (i.e. 5 μM H2O2), and observed a decrease in•OH radicals in both the H2-rich and N2-rich solutions, which may be caused by a decreased dissolved oxygen concentration. Finally, we determined the effect of hydrogen on a high-valence iron enzyme, horseradish peroxidase (HRP), and found that hydrogen could directly increase HRP activity in a dose-dependent manner. Overall, these results indicate that although H2and•OH can react, the reaction rate is too low to have physiological function. The target of hydrogen is more complex, and its interaction with enzymes or other macro-molecules deserve more attention and in-depth study.
Subcellular architecture and metabolic connection in the planktonic photosymbiosis between Collodaria (radiolarians) and their microalgae
Authors: Decelle Johan , Veronesi Giulia , LeKieffre Charlotte , Gallet Benoit , Chevalier Fabien , Stryhanyuk Hryhoriy , Marro Sophie , Ravanel Stéphane , Tucoulou Rémi , Schieber Nicole , Finazzi Giovanni , Schwab Yannick , Musat Niculina
Published: March 2021

Photosymbiosis is widespread and ecologically important in the oceanic plankton but remains poorly studied. Here, we used multimodal subcellular imaging to investigate the photosymbiosis between colonial Collodaria and their microalga dinoflagellate (Brandtodinium) collected in surface seawaters. We showed that this symbiosis is a very dynamic system whereby symbionts interact with different host cells via extracellular vesicles within the “greenhouse-like” colony. 3D electron microscopy revealed that the volume of the photosynthetic apparatus (plastid and pyrenoid) of the microalgae increased in symbiosis compared to free-living while the mitochondria volume was similar. Stable isotope probing coupled with NanoSIMS showed that carbon and nitrogen were assimilated and stored in the symbiotic microalga in starch granules and purine crystals, respectively. Nitrogen was also allocated to the algal nucleus (nucleolus). After 3 hours, low13C and15N transfer was detected in the host Golgi. Metal mapping revealed that intracellular iron concentration was similar in free-living and symbiotic microalgae (ca 40 ppm) and two-fold higher in the host, whereas copper concentration increased in symbiotic microalgae (up to 6900 ppm) and was detected in the host cell and extracellular vesicles. Sulfur mapping also pinpointed the importance of this nutrient for the algal metabolism. This study, which revealed subcellular changes of the morphology and nutrient homeostasis in symbiotic microalgae, improves our understanding on the metabolism of this widespread and abundant oceanic symbiosis and paves the way for more studies to investigate the metabolites exchanged.
A Creb3-Like Transcription Factor Coordinates ER Function upon Food Intake to Regulate Lipid Metabolism
Authors: Khan Haris A. , Toh Ming , Schauer Tamás , Beresford Rory J. , Ortega-Prieto Paula , Postic Catherine , Margulies Carla E.
Published: March 2021

Ingestion of nutrients elicits essential physiological responses, including absorption, digestion, cessation of feeding and nutrient storage. The endoplasmic reticulum (ER) is central to this nutritional homeostasis, since it regulates intracellular organelle function, drives intercellular communication and promotes metabolite distribution. We identified theDrosophilaCreb3L-family transcription factor, CrebA, as the key metabolic regulator of ER function, thereby affecting lipid metabolism and feeding behavior. In response to feeding, CrebA activity is rapidly and transiently activated. CrebA directly drives the expression of the ER protein sorting machinery. We demonstrate that CrebA levels regulate lipid metabolism through lipoprotein secretion into the hemolymph and suppress feeding behavior. Further, CrebA mouse homologs are also upregulated in the liver following feeding and drive the transcriptional activation of ER protein sorting machinery genes in mammals. Our results reveal an evolutionarily conserved transcription switch which is turned on in response to food ingestion and orchestrates a negative feedback loop that promotes satiety by regulating ER function and protein secretion.
Accurate analysis of short read sequencing in complex genomes: A case study using QTL-seq to target blanchability in peanut (Arachis hypogaea)
Authors: Korani Walid , O’Connor Dan , Chu Ye , Chavarro Carolina , Ballen Carolina , Ozias-Akins Peggy , Wright Graeme , Clevenger Josh
Published: March 2021

Next Generation sequencing was a step change for molecular genetics and genomics. Illumina sequencing in particular still provides substantial value to animal and plant genomics. A simple yet powerful technique, referred to as QTL sequencing (QTL-seq) is susceptible to high levels of noise due to ambiguity of alignment of short reads in complex regions of the genome. This noise is particularly high when working with polyploid and/or outcrossing crop species, which impairs the efficacy of QTL-seq in identifying functional variation. By filtering loci based on the optimal alignment of short reads, we have developed a pipeline, named Khufu, that substantially improves the accuracy of QTL-seq analysis in complex genomes, allowingde novovariant discovery directly from bulk sequence. We first demonstrate the pipeline by identifying and validating loci contributing to blanching percentage in peanut using lines from multiple related populations. Using other published datasets in peanut,Brassica rapa, Hordeum volgare, Lactua satvia, andFelis catus, we demonstrate that Khufu produces more accurate results straight from bulk sequence. Khufu works across species, genome ploidy level, and data types. In cases where identified QTL were fine mapped, the fine mapped region corresponds to the top of the peak identified by Khufu. The accuracy of Khufu allows the analysis of population sequencing at very low coverage (<3x), greatly decreasing the amount of sequence needed to genotype even the most complex genomes.
Detection of Chronic Wasting Disease prions in fetal tissuesoffree-ranging white-tailed deer
Authors: Nalls AV , McNulty EE , Mayfield A , Crum JM , Keel MK , Hoover EA , Ruder MG , Mathiason CK
Published: March 2021

The transmission of chronic wasting disease (CWD) has largely been attributed to contact with infectious prions shed in excretions (saliva, urine, feces, blood) by direct animal-to-animal exposure or indirect contact with the environment. Less-well studied has been the role mother-to-offspring transmission may play in the facile transmission of CWD. We asked whether such extensive spread may also be due to mother-to-offspring transmission, perhaps before birth. We thereby focused on a population of white-tailed deer from West Virginia, USA, in which CWD has been detected. Fetal tissues, ranging from 113 to 158 days of gestation, were harvested from the uteri of CWD+ dams in the asymptomatic phase of infection. Using serial protein misfolding amplification (sPMCA), we detected evidence of prion seeds in 6 of 14in uteroharvested fetuses, with earliest detection at 113 gestational days. This is the first report of CWD detection in free ranging white-tailed deer fetal tissues. Further investigation within cervid populations across North America will help define the role and impact of mother-to-offspring vertical transmission of CWD.
Paired feed-forward excitation with delayed inhibition allows high frequency computations across brain regions
Authors: Cao Alexandra S. , Van Hooser Stephen D.
Published: March 2021

The transmission of high-frequency temporal information across brain regions is critical to perception, but the mechanisms underlying such transmission remain unclear. Long-range projection patterns across brain areas are often comprised of paired feedforward excitation followed closely by delayed inhibition, including the thalamic triad synapse, thalamic projections to cortex, and projections within hippocampus. Previous studies have shown that these joint projections produce a shortened period of depolarization, sharpening the timing window over which the postsynaptic neuron can fire. Here we show that these projections can facilitate the transmission of high-frequency computations even at frequencies that are highly filtered by neuronal membranes. This temporal facilitation occurred over a range of synaptic parameter values, including variations in synaptic strength, synaptic time constants, short-term synaptic depression, and the delay between excitation and inhibition. Further, these projections can coordinate computations across multiple network levels, even amid ongoing local activity. We suggest that paired feedforward excitation and inhibition provides a hybrid signal – carrying both a value and a clock-like trigger – to allow circuits to be responsive to input whenever it arrives.
Discrete ripples reflect a spectrum of synchronous spiking activity in human association cortex
Authors: Tong Ai Phuong S. , Vaz Alex P. , Wittig John H. , Inati Sara K. , Zaghloul Kareem A.
Published: March 2021

Direct brain recordings have provided important insights into how persistent oscillatory activity support human memory retrieval, but the extent to which transient fluctuations in intracranial EEG (iEEG) captures the dynamic coordination of underlying neurons involved in memory processing remains unclear. Here, we simultaneously record iEEG, local field potential (LFP), and single unit activity in the human temporal cortex. We demonstrate that cortical ripples contribute to broadband high frequency activity and exhibit a spectrum of amplitudes and durations related to the amount of underlying neuronal spiking. Ripples in the macro-scale iEEG are related to the number and synchrony of ripples in the micro-scale LFP, which in turn are related to the synchrony of neuronal spiking. Our data suggest that neural activity in the human cortex is organized into dynamic, discrete packets of information.
Redox Buffering Capacity of Nanomaterials as an Index of ROS-based Therapeutics and Toxicity: A Preclinical Animal Study
Authors: Adhikari Aniruddha , Mondal Susmita , Das Monojit , Ghosh Ria , Biswas Pritam , Darbar Soumendra , Singh Soumendra , Das Anjan Kumar , Bhattacharya Siddhartha Sankar , Pal Debasish , Mallick Asim Kumar , Pal Samir Kumar
Published: March 2021

Precise control of intracellular redox status, i.e., maintenance of physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress) is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, or depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate functionalized trimanganese tetroxide nanoparticles (C-Mn3O4NPs) as a model nanosystem we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in animal model in order to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use.
Redox Nanomedicine Cures Chronic Kidney Disease (CKD) by Mitochondrial Reconditioning
Authors: Adhikari Aniruddha , Mondal Susmita , Chatterjee Tanima , Das Monojit , Biswas Pritam , Darbar Soumendra , Alessa Hussain , Al-Thakafy Jalal T. , Sayqal Ali , Ahmed Saleh A. , Das Anjan Kumar , Bhattacharyya Maitree , Pal Samir Kumar
Published: March 2021

Targeting reactive oxygen species (ROS) while maintaining cellular redox signaling is crucial in the development of redox medicine for the therapeutic benefit as the origin of several prevailing diseases including chronic kidney disease (CKD) is linked to ROS imbalance and associated mitochondrial dysfunction. Here, we have shown that an indigenously developed nanomedicine comprising of Mn3O4nanoparticles duly functionalized by biocompatible ligand citrate (C-Mn3O4NPs) can maintain cellular redox balance in an animal model. We developed a cisplatin-induced CKD model in C57BL/6j mice where severe mitochondrial dysfunction resulting in oxidative distress lead to the pathogenesis. Four weeks of treatment with C-Mn3O4NPs restored renal function, preserved normal kidney architecture, ameliorated overexpression of pro-inflammatory cytokines, and arrested glomerulosclerosis and interstitial fibrosis in CKD mice. A detailed study involving human embryonic kidney (HEK 293) cells and isolated mitochondria from experimental animals revealed that the molecular mechanism behind the pharmacological action of the nanomedicine involves protection of structural and functional integrity of mitochondria from oxidative damage, the subsequent reduction in intracellular ROS, and maintenance of cellular redox homeostasis. To the best of our knowledge, such studies that efficiently treated a multifaceted disease like CKD using a biocompatible redox nanomedicine are sparse in the literature. Successful clinical translation of this nanomedicine may open a new avenue in redox-mediated therapeutics of several other diseases (e.g., diabetic nephropathy, neurodegeneration, and cardiovascular disease) where oxidative distress plays a central role in pathogenesis.
Ozone nanobubble treatments improve survivability of Nile tilapia (Oreochromis niloticus) challenged with a pathogenic multidrug-resistantAeromonas hydrophila
Authors: Dien Le Thanh , Vu Linh Nguyen , Sangpo Pattiya , Senapin Saengchan , St-Hilaire Sophie , Rodkhum Channarong , Dong Ha Thanh
Published: March 2021

Multidrug-resistant (MDR) bacteria has rapidly increased in aquaculture, which highlights the risk of production losses due to diseases and potential public health concerns. Previously, we reported that ozone nanobubbles (NB-O3) were effective at reducing concentrations of pathogenic bacteria in water and modulating fish immunity against pathogens; however, multiple treatments with direct NB-O3exposures caused alterations to the gills of exposed-fish. Here, we set up a modified recirculation system (MRS) assembled with an NB-O3device (MRS-NB-O3) to investigate whether MRS-NB-O3were 1) safe for tilapia (Oreochromis niloticus), 2) effective at reducing bacterial load in rearing water, and 3) improved survivability of Nile tilapia following an immersion challenge with a lethal dose of MDRAeromonas hydrophila. The results indicated no behavioral abnormalities or mortality of Nile tilapia during the 14 day study using the MRS-NB-O3system. In the immersion challenge, although high bacterial concentration (~2 × 107CFU/mL) was used, multiple NB-O3treatments in the first two days reduced the bacteria between 15.9% to 35.6% of bacterial load in water while bacterial concentration increased 13.1% to 27.9% in the untreated control. There was slight up-regulation of non-specific immune-related genes in the gills of the fish receiving NB-O3treatments. Most importantly, this treatment significantly improved survivability of Nile tilapia with relative percent survival (RPS) of 64.7 - 66.7% in treated fish and surviving fish developed specific antibody against MDRA. hydrophila. In summary, the result suggests that NB-O3is a promising alternative to antibiotics to control bacterial diseases, including MDR bacteria, and has high potential for application in recirculation aquaculture system (RAS).

Highlights

Multiple treatments of NB-O3in a modified recirculation system (MRS) were relatively safe for juvenile Nile tilapia

NB-O3treatments in MRS significantly improved survivability of Nile tilapia challenged with multidrug-resistant (MDR)A. hydrophilawith RPS of 64.7 - 66.7%

Concentration of MDRA. hydrophilain MRS was reduced by 15.9 to 35.6% following each NB-O3treatment, and increased by 13.1 to 27.9 % in untreated control

Surviving fish developed specific antibody IgM against MDRA. hydrophila

NB-O3is a promising non-antibiotic approach to control diseases caused by MDRA. hydrophila
BEdeepoff: anin silicotool for off-target prediction of ABE and CBE base editors
Authors: Zhang Chengdong , Wang Daqi , Qi Tao , Zhang Yuening , Hou Linghui , Lan Feng , Yang Jingcheng , Ong Sang-Ging , Wang Hongyan , Shi Leming , Wang Yongming
Published: March 2021

Base editors, including adenine base editors (ABEs) and cytosine base editors (CBEs), are valuable tools for introducing point mutations, but they frequently induce unwanted off-target mutations. Here, we performed a high-throughput gRNA-target library screening to measure editing efficiencies at integrated genomic off-targets and obtained datasets of 48,632 and 52,429 off-targets for ABE and CBE, respectively. We used the datasets to train deep learning models, resulting in ABEdeepoff and CBEdeepoff which can predict editing efficiencies at off-targets. These tools are freely accessible via online web serverhttp://www.deephf.com/#/bedeep.
BEdeepon: an in silico tool for prediction of base editor efficiencies and outcomes
Authors: Zhang Chengdong , Yu Zimeng , Wang Daqi , Qi Tao , Zhang Yuening , Hou Linghui , Lan Feng , Yang Jingcheng , Shi Leming , Ong Sang-Ging , Wang Hongyan , Wang Yongming
Published: March 2021

Base editors enable direct conversion of one target base into another in a programmable manner, but conversion efficiencies vary dramatically among different targets. Here, we performed a high-throughput gRNA-target library screening to measure conversion efficiencies and outcome product frequencies at integrated genomic targets and obtained datasets of 60,615 and 73,303 targets for ABE and CBE, respectively. We used the datasets to train deep learning models, resulting in ABEdeepon and CBEdeepon which can predict on-target efficiencies and outcome sequence frequencies. The software is freely accessible via online web serverhttp://www.deephf.com/#/bedeep/bedeepon.
Event-related and oscillatory signatures of response inhibition: A magnetoencephalography study with subclinical high and low impulsivity adults
Authors: Jauregi Ainara , Wang Hongfang , Hassel Stefanie , Kessler Klaus
Published: March 2021

Inhibition, the ability to withhold a response or to stop an initiated response, is a necessary cognitive function that can be vulnerable to an impairment. High levels of impulsivity have been shown to impact response inhibition and/or cognitive task performance. The present study investigated the spectral and spatio-temporal dynamics of response inhibition, during a combined go/no-go/stop-signal task, using magnetoencephalography (MEG) in a healthy undergraduate student population. Participants were divided by their level of impulsivity, as assessed by self-report measures, to explore potential differences between high (n=17) and low (n=17) impulsivity groups. Results showed that individuals scoring high on impulsivity failed significantly more NOGO and STOP trials than those scoring low, but no significant differences were found between stop-signal reaction times. During NOGO and STOP conditions, high impulsivity individuals showed significantly smaller M1 components in posterior regions, which could suggest an attentional processing deficit. During NOGO trials, the M2 component was found to be reduced in individuals scoring high, possibly reflecting less pre-motor inhibition efficiency, whereas in STOP trials, the network involved in the stopping process was engaged later in high impulsivity individuals. The high impulsivity group also engaged frontal networks more during the STOP-M3 component only, possibly as a late compensatory process. The lack of response time differences on STOP trials could indicate that compensation was effective to some degree (at the expense of higher error rates). Decreased frontal delta and theta band power was observed in high impulsivity individuals, suggesting a possible deficit in frontal pathways involved in motor suppression, however, unexpectedly, increased delta and theta band power in central and posterior sensors was also observed, which could be indicative of an increased effort to compensate for frontal deficits. Individuals scoring highly also showed decreased alpha power in frontal sensors, suggesting decreased inhibitory processing, along with reduced alpha suppression in posterior regions, reflecting reduced cue processing. These results provide evidence for how personality traits, such as impulsivity, relate to differences in the neural correlates of response inhibition.
AKAP79 enables calcineurin to directly suppress protein kinase A activity
Authors: Church Timothy W. , Tewatia Parul , Hannan Saad , Antunes João , Eriksson Olivia , Smart Trevor G. , Kotaleski Jeanette Hellgren , Gold Matthew G.
Published: March 2021

Interplay between the second messengers cAMP and Ca2+is a hallmark of dynamic cellular processes. A common motif is the opposition of the Ca2+-sensitive phosphatase calcineurin and the major cAMP receptor, protein kinase A (PKA). Calcineurin dephosphorylates sites primed by PKA to bring about changes including synaptic long-term depression (LTD). AKAP79 supports signaling of this type by anchoring PKA and calcineurin in tandem. In this study, we discovered that AKAP79 increases the rate of calcineurin dephosphorylation of type II PKA regulatory subunits by an order of magnitude. Fluorescent PKA activity reporter assays, supported by kinetic modeling, show how AKAP79-enhanced calcineurin activity enables suppression of PKA without altering cAMP levels by increasing PKA catalytic subunit capture rate. Experiments with hippocampal neurons indicate that this mechanism contributes towards LTD. This non- canonical mode of PKA regulation may underlie many other cellular processes.