bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure mechanisms and bending strength of
Fuchsia magellanica
var.
gracilis
stems
Authors: Hone Timothy , Mylo Max , Speck Olga , Speck Thomas , Taylor David
Published: February 2021

In the course of biological evolution, plant stems have evolved mechanical properties and an internal structure that makes them resistant to various types of failure. The mechanisms involved during damage development and failure in bending are complex and incompletely understood. The work presented builds on a theoretical framework outlined by Ennos and van Casteren, who applied engineering mechanics theory to explain why different woody stems fail in different ways. Our work has extended this approach, applying it to a detailed analysis of one particular species:
Fuchsia magellanica
var.
gracilis
. When subjected to three-point bending, stems of this species exhibited one of two failure mechanisms: a plastic hinge or a greenstick fracture. We developed a predictive model using a computer simulation and a mathematical analysis using the theory of plastic bending. Required material properties were obtained from tests, the literature and imaging techniques. We found that greenstick fractures are more likely to occur in more lignified stems with a higher density. We discovered a new failure mode: an internal crack caused by tensile transverse stress. This work helps in understanding how plants have evolved their bending resistance and may assist in the creation of novel engineering structures inspired by these principles.
Should We Delay the Second COVID-19 Vaccine Dose in Order to Optimize Rollout? A Mathematical Perspective
Authors: Berkane Soulaimane , Harizi Intissar , Tayebi Abdelhamid , Silverman Michael S. , Stranges Saverio
Published: February 2021

Objectives

With vaccination shortage persisting in many countries, adopting an optimal vaccination program is of crucial importance. Given the slow pace of vaccination campaigns globally, a very relevant and burning public health question is whether it is better to delay the second COVID-19 vaccine shot until all priority group people have received at least one shot. Currently, many countries are looking to administer a third dose (booster shot), which raises the question of how to distribute the available daily doses to maximize the effectively vaccinated population.

Methods

We formulate a generalized optimization problem with a total of vaccine doses, that have to be optimally distributed between n different sub-populations, where sub-population ui represents people receiving the i-th dose of the vaccine with efficacy αi. The particular case where n = 2 is solved first, followed by the general case of n dose regimen.

Results

In the case of a two dose regimen, if the efficacy of the second dose is less than (or equal to) twice the efficacy of the first dose, the optimal strategy to maximize the number of effectively vaccinated people is to delay the second vaccine as much as possible. Otherwise, the optimal strategy would consist of administering the second dose as quickly as possible. In the general case, the optimal vaccination strategy would be to administer the k−th dose corresponding to the index providing the maximum inter-dose efficacy difference (αi − αi−1) for all possible values of i ∈ {1, …, n}, with α0 = 0.

Conclusion

Our results suggest that although extending the interval between doses beyond 12 weeks was likely optimal earlier in the pandemic, the reduced single dose efficacy of vaccines against the delta variant make this approach no longer viable.
Endothelial cells elicit a pro-inflammatory response to SARS-CoV-2 without productive viral infection
Authors: Schimmel Lilian , Chew Keng Yih , Stocks Claudia , Yordanov Teodor , Essebier Patricia , Kulasinghe Arutha , Monkman James , Miggiolaro Anna Flavia Ribeiro dos Santos , Cooper Caroline , de Noronha Lucia , Lagendijk Anne K. , Schroder Kate , Labzin Larisa I. , Gordon Emma J. , Short Kirsty R.
Published: February 2021

Objectives

Thrombotic and microvascular complications are frequently seen in deceased COVID-19 patients. However, whether this is caused by direct viral infection of the endothelium or inflammation-induced endothelial activation remains highly contentious.

Methods

Here, we use patient autopsy samples, primary human endothelial cells and anin vitromodel of the pulmonary epithelial-endothelial cell barrier to show that primary human endothelial cells express very low levels the SARS-CoV-2 receptor ACE2 and the protease TMPRSS2.

Results

Accordingly, endothelial cells can only be infected when SARS-CoV-2 is present at very high concentrations. However, this is not a productive infection (i.e. no infectious virus is produced) and viral entry induces an inflammatory response. We also show that SARS-CoV-2 does not infect endothelial cells in 3D vessels under flow conditions. We further demonstrate that in a co-culture model endothelial cells are not infected with SARS-CoV-2. They do however sense and respond to infection in the adjacent epithelial cells, increasing ICAM-1 expression and releasing pro-inflammatory cytokines.

Conclusions

Taken together, these data suggest thatin vivo, endothelial cells are unlikely to be infected with SARS-CoV-2 and that infection is only likely to occur if the adjacent pulmonary epithelium is denuded (basolateral infection) or a high viral load is present in the blood (apical infection). In such a scenario, whilst SARS-CoV-2 infection of the endothelium can occur, it does not contribute to viral amplification. However, endothelial cells are still likely to play a key role in SARS-CoV-2 pathogenesis by sensing adjacent infection and mounting a pro-inflammatory response to SARS-CoV-2.
Epidemiological, Clinical Characteristics and Risk Factors for Severe Condition and ICU Admission of COVID-19 Patients of Early Stage in China: A review
Authors: Fu Qinwei , Wu Wenjuan , Liu Yang , Huang Heyin , Zhang Peihai , Li Xinrong , Liu Ying , Zhang Lanzhi , Yang Hui , Zhang Xin , Zhang Qinxiu , Huang Chaolin
Published: February 2021

Objective

Some retrospective studies reporting epidemiological, clinical characteristics of COVID-19 patients of early stage were published. We aim to provide an overview of epidemiological and clinical characteristics of the COVID-19 patients, and identification, treatment of early stage, especially for the patients with poor prognosis.

Data Sources

PubMed, CNKI and Google Scholar.

Study Selection

We searched for published retrospective studies that described epidemiological and clinical characteristics of confirmed COVID-19 patients in China by April 14th, 2020 with search terms. Some studies were excluded according to criteria. Finally, 53 studies were included.

Data Extraction

Characteristics of the COVID-19 patients available from included articles were extracted, reorganized and recorded into electronic data forms.

Data Synthesis

Characteristics of patients in the included studies were summarized and analyzed for median-interquartile ranges and univariable odds ratio.

Conclusion

This study summarized, analyzed and compared epidemiological, clinical characteristics and estimated univariable risk factors among confirmed COVID-19 patients either in former epicenter, in severe condition, with ICU admission or not of early stage. Higher proportions of patients were found to have older age and more comorbidities, typical characteristics on admission and complications either in former epicenter, with severe condition or ICU admission. No evidence showed that patients who were male or had smoking history had higher susceptibility, but they were significant risk factors for severe condition. Some self-implementable traditional Chinese medicine therapies conducted for immunity improvement, control of comorbidities and reduction of some medicine intake. Limited evidence revealed that some characteristics of the disease might be changing with human-to-human transmission, and more research, especially international collaboration, is needed.

Copyright form disclosure

The authors have disclosed that they do not have any potential conflicts of interest.
Epidemiological dynamics of the incidence of COVID-19 in children and the relationship with the opening of schools in Catalonia (Spain)
Authors: Perramon Aida , Soriano-Arandes Antoni , Pino David , Lazcano Uxue , Andrés Cristina , Català Martí , Gatell Anna , Carulla Mireia , Canadell Dolors , Ricós Gemma , Riera-Bosch Ma Teresa , Burgaya Silvia , Salvadó Olga , Cantero Javier , Vilà Mònica , Poblet Miriam , Sánchez Almudena , Ma Ristol Anna , Serrano Pepe , Antón Andrés , Prats Clara , Soler-Palacin Pere
Published: February 2021

Here we analyse the epidemiological trend of the incidence of COVID-19 in children in Catalonia (Spain) during the first 20 weeks of the 2020-2021 school year. This study demonstrates that while schools were open the incidence rate among children remained significantly lower than in general population, despite a greater diagnostic effort in children. These results suggest that schools have not played a significant role in the SARS-CoV-2 dissemination in Catalonia.
Teaching an Old Dog New Tricks: Serum Troponin T as a Biomarker in Amyotrophic Lateral Sclerosis
Authors: Castro-Gomez Sergio , Radermacher Barbara , Tacik Pawel , Mirandola Sandra R. , Heneka Michael T. , Weydt Patrick
Published: February 2021

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Diagnosis, management and therapeutic trials are hampered by a lack of informative biomarkers. Troponins (Tn) are components of skeletal and cardiac muscles. Acute elevation of cardiac isoforms of troponin I (cTnI) and T (cTnT) in serum indicates myocardial injury. Case reports suggested that serum levels of cTnT, but not cTnI are chronically elevated in ALS and other neuromuscular disorders.

Using standard clinical laboratory methodologies we studied serum troponin levels in a multicentric cross-sectional cohort of 75 ALS patients and sixty controls (DESCRIBE-ALS cohort) and in a real-world cohort of 179 consecutive patients from our ALS clinic at the University Hospital Bonn.

We found that serum cTnT, is elevated in >60% of ALS patients while cTnI is always normal. Serum cTnT levels increase over time and correlate with disease severity as measured with the revised ALS FRS score. There was no correlation with the phosphorylated neurofilament heavy chain (pNfH) levels in the cerebrospinal fluid. We propose that cTnT elevations in ALS are of non-cardiac origin and may serve as a proxy of lower motor neuron or skeletal muscle involvement. They potentially help to stratify patients according to lower motoneuron involvement. Further research will determine the biological origin of the cTnT elevation and its validity as a diagnostic and/or prognostic marker. Our finding also serves as a reminder to interpret cTnT with caution elevations in patients with neuromuscular diseases.
Detection of a biolistic delivery of fluorescent markers and CRISPR/Cas9 to the pollen tube
Authors: Nagahara Shiori , Higashiyama Tetsuya , Mizuta Yoko
Published: February 2021

In recent years, genome-editing techniques, such as the CRISPR/Cas9 system, have been highlighted as a new approach to plant breeding.Agrobacterium-mediated transformation has been widely utilized to generate transgenic plants by introducing plasmid DNA containing CRISPR/Cas9 into plant cells. However, this method is generally applicable to a limited range of plants, such as model species. To overcome this limitation, we developed a method to genetically modify male germ cells without the need forAgrobacterium-mediated transfection and tissue culture, by using tobacco as a model. In this study, plasmid DNA containing sequences of Cas9, guide RNA, and fluorescent reporter was introduced into pollen using a biolistic delivery system. Based on the transient expression of fluorescent reporters, theArabidopsis UBQ10promoter was found to be the most suitable for driving expression of the delivered gene in pollen tubes. We also evaluated delivery efficiency in male germ cells in the pollen by expression of the introduced fluorescent marker. Mutations were detected in the target gene in the genomic DNA extracted from CRISPR/Cas9 introduced pollen tubes but were not detected in the negative control. Bombarded pollen germinated pollen tubes on the stigma and produced two sperm cells within the pistil. We also observed ovules showing fluorescence derived from bombarded pollen. The findings of this study provide important insights into the editing of pollen tube genomes and the delivery of genome-modified male germ cells for seed production.
Perception of invisible masked objects in early infancy
Authors: Nakashima Yusuke , Kanazawa So , Yamaguchi Masami K.
Published: February 2021

Recurrent loops in the visual cortex play a critical role in visual perception, which is likely not mediated by purely feedforward pathways. However, the development of recurrent loops is poorly understood. The role of recurrent processing has been studied using visual backward masking, a perceptual phenomenon in which a visual stimulus is rendered invisible by a following mask, possibly because of the disruption of recurrent processing. Anatomical studies have reported that recurrent pathways are immature in early infancy. This raises the possibility that younger infants process visual information mainly in a feedforward manner, and thus, they might be able to perceive visual stimuli that adults cannot see because of backward masking. Here, we show that infants under 7 months of age are immune to visual backward masking and that masked stimuli remain visible to younger infants while older infants cannot perceive them. These results suggest that recurrent processing is immature in infants under 7 months and that they are able to perceive objects even without recurrent processing. Our findings indicate that the algorithm for visual perception drastically changes in the second half of the first year of life.
Single-Domain SARS-CoV-2 S1 and RBD Antibodies Isolated from Immunized Llama Effectively Bind Targets of the Wuhan, UK, and South African Strains in vitro
Authors: Yemane Divora , Lu Ivan , Tiahjono Winson , Rubidoux Lauren , Hussain Abbas , Cancilla John C. , Duggan Erika , Shaner Nathan C. , Nakanishi Nobuki , Wang Jiwu
Published: February 2021

The spreading of SARS-CoV-2 variants has become a major challenge of the current fight against the pandemic. Of particular concerns are the strains that have arisen from the United Kingdom (UK) and South Africa. The UK variant spreads rapidly and is projected to overtake the original strain in the US as early as in March 2021, while the South African variant appears to evade some effects of the current vaccines. Potential false-negative diagnosis using currently available antigen kits that may not recognize these variants could cause another wave of community infection. Therefore, it is imperative that antibodies used in the detection kits are validated for binding against these variants. Here we report that the nanoantibodies (nAbs in our terminology, also referred to as VHH fragments, single domain antibodies, nanobodies™) that we have developed for rapid antigen detection test bind the receptor binding domain (RBD) of the S1 protein from the original COVID-SARS-2 virus as well as those from the UK and South African variants. This finding validates our antibodies used in our assay for the detection of these major variant strains.
Reexamination of N-terminal domains of Syntaxin-1 in vesicle fusion from central murine synapses
Authors: Vardar Gülçin , Salazar-Lázaro Andrea , Brockmann Marisa , Weber-Boyvat Marion , Zobel Sina , Kumbol Victor Wumbor-Apin , Trimbuch Thorsten , Rosenmund Christian
Published: February 2021

Syntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight binary complex through two major binding modes: one through STX1’s N-peptide, the other through STX1’s closed conformation driven by its Habc-domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1’s N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1’s N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1’s open conformation governs the vesicle fusogenicity. Strikingly, we also show that neurotransmitter release still proceeds when both the interaction modes between STX1 and Munc18-1 are presumably intervened together, necessitating a refinement of the conceptualization of STX1–Munc18-1 interaction.
Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases
Authors: Deakin Claire T. , Cornish Georgina H. , Ng Kevin W. , Faulkner Nikhil , Bolland William , Panova Veera , Hope Joshua , Rosa Annachiara , Harvey Ruth , Hussain Saira , Earl Christopher , Jebson Bethany R. , Wilkinson Meredyth G.Ll. , Marshall Lucy R. , O’Brien Kathryn , Rosser Elizabeth C. , Radziszewska Anna , Peckham Hannah , Heaney Judith , Rickman Hannah , Paraskevopoulou Stavroula , Houlihan Catherine F. , Spyer Moira J. , Gamblin Steve J. , McCauley John , Nastouli Eleni , Cherepanov Peter , Ciurtin Coziana , Wedderburn Lucy R. , Kassiotis George
Published: February 2021

Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies.
Corollary discharge prevents signal distortion and enhances sensing during locomotion
Authors: Skandalis Dimitri A. , Lunsford Elias T. , Liao James C.
Published: February 2021

Sensory feedback during movement entails sensing a mix of externally- and self-generated stimuli (respectively, exafference and reafference). In many peripheral sensory systems, a parallel copy of the motor command, a corollary discharge, is thought to eliminate sensory feedback during behaviors. However, reafference has important roles in motor control, because it provides real-time feedback on the animal’s motions through the environment. In this case, the corollary discharge must be calibrated to enable feedback while avoiding negative consequences like sensor fatigue. The undulatory motions of fishes’ bodies generate induced flows that are sensed by the lateral line sensory organ, and prior work has shown these reafferent signals contribute to the regulation of swimming kinematics. Corollary discharge to the lateral line reduces the gain for reafference, but cannot eliminate it altogether. We develop a data-driven model integrating swimming biomechanics, hair cell physiology, and corollary discharge to understand how sensory modulation is calibrated during locomotion in larval zebrafish. In the absence of corollary discharge, lateral line afferent units exhibit the highly heterogeneous habituation rates characteristic of hair cell systems, typified by decaying sensitivity and phase distortions with respect to an input stimulus. Activation of the corollary discharge prevents habituation, reduces response heterogeneity, and regulates response phases in a narrow interval around the time of the peak stimulus. This suggests a synergistic interaction between the corollary discharge and the polarization of lateral line sensors, which sharpens sensitivity along their preferred axes. Our integrative model reveals a vital role of corollary discharge for ensuring precise feedback, including proprioception, during undulatory locomotion.
Cerebellar tDCS alters the perception of optic flow
Authors: Nankoo Jean-François , Madan Christopher R , Medina Omar , Makepeace Tyler , Striemer Christopher L.
Published: February 2021

Studies have shown that the cerebellar vermis is involved in the perception of motion. However, it is unclear how the cerebellum influences motion perception. tDCS is a non-invasive brain stimulation technique that can reduce (through cathodal stimulation) or increase neuronal excitability (through anodal stimulation). To explore the nature of the cerebellar involvement on large-field global motion perception (i.e., optic flow-like motion), we applied tDCS on the cerebellar midline while participants performed an optic flow motion discrimination task. Our results show that anodal tDCS improves discrimination threshold for optic flow perception, but only for left-right motion in contrast to up-down motion discrimination. This result was evident within the first 10 minutes of stimulation and was also found post-stimulation. Cathodal stimulation did not have any significant effects on performance in any direction. The results show that discrimination of planar optic flow can be improved with tDCS of the cerebellar midline and provide further support for the role of the human midline cerebellum in the perception of optic flow.
Fibrin Polymer on the Surface of Biomaterial Implants Drives the Foreign Body Reaction
Authors: Balabiyev Arnat , Podolnikova Nataly P. , Kilbourne Jacquelyn A. , Baluch D. Page , Lowry David , Zare Azadeh , Ros Robert , Flick Matthew J. , Ugarova Tatiana P.
Published: February 2021

ABSTRACT

Implantation of biomaterials and medical devices in the body triggers the foreign body reaction (FBR) which is characterized by macrophage fusion at the implant surface leading to the formation of foreign body giant cells and the development of the fibrous capsule enveloping the implant. While adhesion of macrophages to the surface is an essential step in macrophage fusion and implanted biomaterials are known to rapidly acquire a layer of host proteins, a biological substrate that is responsible for this processin vivois unknown. Here we show that mice with genetically-imposed fibrinogen deficiency display a dramatic reduction of macrophage fusion on implanted biomaterials and are protected from the formation of fibrin-containing granulation tissue, a precursor of the fibrous capsule. Furthermore, macrophage fusion on biomaterials implanted in FibAEKmice that express a mutated form of fibrinogen incapable of thrombin-mediated polymerization was strongly reduced. Surprisingly, despite the lack of fibrin, the capsule was formed in FibAEKmice, although it had a different composition and distinct mechanical properties than that in wild-type mice. Specifically, while mononuclear α-SMA-expressing macrophages embedded in the capsule of both strains of mice secreted collagen, the amount of collagen and its density in the tissue of FibAEKmice was reduced. These data identify fibrin polymer as a key biological substrate driving the development of the FBR.
The Host Interactome of Spike Expands the Tropism of SARS-CoV-2
Authors: Bamberger Casimir , Pankow Sandra , Martínez-Bartolomé Salvador , Diedrich Jolene , Park Robin , Yates John
Published: February 2021

The SARS-CoV-2 virus causes severe acute respiratory syndrome (COVID-19) and has rapidly created a global pandemic. Patients that survive may face a slow recovery with long lasting side effects that can afflict different organs. SARS-CoV-2 primarily infects epithelial airway cells that express the host entry receptor Angiotensin Converting Enzyme 2 (ACE2) which binds to spike protein trimers on the surface of SARS-CoV-2 virions. However, SARS-CoV-2 can spread to other tissues even though they are negative for ACE2. To gain insight into the molecular constituents that might influence SARS-CoV-2 tropism, we determined which additional host factors engage with the viral spike protein in disease-relevant human bronchial epithelial cells (16HBEo−). We found that spike recruited the extracellular proteins laminin and thrombospondin and was retained in the endoplasmatic reticulum (ER) by the proteins DJB11 and FBX2 which support re-folding or degradation of nascent proteins in the ER. Because emerging mutations of the spike protein potentially impact the virus tropism, we compared the interactome of D614 spike with that of the rapidly spreading G614 mutated spike. More D614 than G614 spike associated with the proteins UGGT1, calnexin, HSP7A and GRP78/BiP which ensure glycosylation and folding of proteins in the ER. In contrast to G614 spike, D614 spike was endoproteolytically cleaved, and the N-terminal S1 domain was degraded in the ER even though C-terminal ‘S2 only’ proteoforms remained present. D614 spike also bound more laminin than G614 spike, which suggested that extracellular laminins may function as co-factor for an alternative, ‘S2 only’ dependent virus entry. Because the host interactome determines whether an infection is productive, we developed a novel proteome-based cell type set enrichment analysis (pCtSEA). With pCtSEA we determined that the host interactome of the spike protein may extend the tropism of SARS-CoV-2 beyond mucous epithelia to several different cell types, including macrophages and epithelial cells in the nephron. An ‘S2 only’ dependent, alternative infection of additional cell types with SARS-CoV-2 may impact vaccination strategies and may provide a molecular explanation for a severe or prolonged progression of disease in select COVID-19 patients.
Reporter gene assay for membrane fusion of extracellular vesicles
Authors: Somiya Masaharu , Kuroda Shun’ichi
Published: February 2021

Extracellular vesicles (EVs) secreted by living cells are expected to deliver biological cargo molecules, including RNA and proteins, to the cytoplasm of recipient cells. There is an increasing need to understand the mechanism of intercellular cargo delivery by EVs. However, the lack of a feasible bioassay has hampered our understanding of the biological processes of EV uptake, membrane fusion, and cargo delivery to recipient cells. Here, we describe a reporter gene assay that can measure the membrane fusion efficiency of EVs during cargo delivery to recipient cells. When EVs containing tetracycline transactivator (tTA)-fused tetraspanins are internalized by recipient cells and fuse with cell membranes, the tTA domain is exposed to the cytoplasm and cleaved by protease to induce tetracycline responsive element (TRE)-mediated reporter gene expression in recipient cells. This assay (designated asEV-mediatedtetraspanin-tTAdelivery assay, ETTD assay), enabled us to assess the cytoplasmic cargo delivery efficiency of EVs in recipient cells. With the help of a vesicular stomatitis virus-derived membrane fusion protein, the ETTD assay could detect significant enhancement of cargo delivery efficiency of EVs. Furthermore, the ETTD assay could evaluate the effect of potential cargo delivery enhancers/inhibitors. Thus, the ETTD assay may contribute to a better understanding of the underlying mechanism of the cytoplasmic cargo delivery by EVs.
A systems-level analysis of dynamic total-body PET data reveals complex skeletal energy metabolism networksin vivo
Authors: Suchacki Karla J. , Alcaide-Corral Carlos J. , Nimale Samah , Macaskill Mark G. , Stimson Roland H. , Farquharson Colin , Freeman Tom C. , Tavares Adriana A. S.
Published: February 2021

Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary, limiting our ability to assess systemic mechanisms underlying diseases and develop novel therapeutics.In vitromolecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactionsin vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactionsin vivousing total-body positron emission tomography (PET) network analysis of murine18F-FDG scans, as a biomarker of glucose metabolism signature in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network. These data could have important therapeutic implications in the management of the metabolic syndrome and skeletal disease. The application of our approach to clinical and preclinical total-body PET studies promises to reveal further physiological and pathological tissue interactions, which simplistic PET standard uptake values analysis fail to interrogate, extending beyond skeletal metabolism, due to the diversity of PET radiotracers available and under development as well as the advent of clinical total-body PET systems.

One Sentence Summary

Bones form a complex metabolic network.
Transcriptome sequence reveals candidate genes involving in the post-harvest hardening of trifoliate yamDioscorea dumetorum
Authors: Siadjeu Christian , Mayland-Quellhorst Eike , Laubinger Sascha , Albach Dirk C.
Published: February 2021

Storage ability ofD. dumetorumis restricted by a severe phenomenon of post-harvest hardening which starts 72h after harvest and renders tubers inedible. Previous work has only focused on the biochemistry changes affecting the PHH onD. dumetorum. To the best of our knowledge nobody has identified candidate genes responsible for hardness onD. dumetorum. Here, transcriptome analysis ofD. dumetorumtubers was performed, 4 months after emergence (4MAE), after harvest (AH), 3 days AH (3DAH) and 14 days AH (14DAH) on four accessions using RNA-Seq. In total between AH and 3DAH, 165, 199,128 and 61 differentially expressed genes (DEGs) were detected in Bayangam 2, Fonkouankem 1, Bangou 1 and Ibo sweet 3 respectively. Functional analysis of DEGs revealed that genes encoding for cellulose synthase A, xylan O-acetyltransferase chlorophyll a/b binding protein 1,2,3,4 and transcription factor MYBP were found predominantly and significantly up-regulated 3DAH, implying that genes were potentially involved in the post-harvest hardening. A hypothetical mechanism of this phenomenon and its regulation has been proposed. These findings provide the first comprehensive insights into genes expression in yam tubers after harvest and valuable information for molecular breeding against the post-harvest hardening. A hypothetical mechanism of this phenomenon and its regulation has been proposed. These findings provide the first comprehensive insights into genes expression in yam tubers after harvest and valuable information for molecular breeding against the post-harvest hardening.
Anthracyclins increase free PUFAs and etherPEs with PUFAs as potential hallmarks of lipid peroxidation and ferroptosis
Authors: Balgoma David , Kullenberg Fredrik , Calitz Carlemi , Kopsida Maria , Heindryckx Femke , Lennernäs Hans , Hedeland Mikael
Published: February 2021

Metabolic and personalized interventions in cancer treatment require a better under-standing of the relationship between the induction of cell death and metabolism. Consequently, we treated three primary liver cancer cell lines with two anthracyclins (doxorubicin and idarubin) and studied the changes of the lipidome. We found that both anthracyclins in the three cell lines increased the levels of polyunsaturated fatty acids (PUFAs) and alkylacylglycerophosphoethano-lamines (etherPEs) with PUFAs. As PUFAs and alkylacylglycerophospholipids with PUFAs are fundamental in lipid peroxidation during ferroptotic cell death, our results suggests supplementa-tion with PUFAs and/or etherPEs with PUFAs as a potential general adjuvant of anthracyclins. In contrast, neither the markers of de novo lipogenesis nor cholesterol lipids presented the same trend in all cell lines and treatments. In agreement with previous research, this suggests that modulation of the metabolism of cholesterol could be considered a specific adjuvant of anthracyclins depend-ing on the type of tumor and the individual. Finally, we discuss the changes in the lipidome in re-lation to the endoplasmic reticulum stress and the sensitivity to anthracyclins of the different cells. In conclusion, our results suggest that the modulation of different lipid metabolic pathways may be considered for generalized and personalized metabochemotherapies.
Disentangling the relative importance of spatio-temporal parameters and host selectivity in shaping AMF communities in temperate forests
Authors: Grünfeld Leonie , Mola Magkdi , Wulf Monika , Hempel Stefan , Veresoglou Stavros D
Published: February 2021

Many woody and herbaceous plants in temperate forests cannot establish and survive in the absence of mycorrhizal associations. Here, we address and hierarchize how Glomeromycota, a group of soil-borne fungi, forming a ubiquitous type of mycorrhiza, varied in a temperate forest patch in Germany with time, space, plant hosts but also the proximity to Glomeromycota-associating woody species. The communities of Glomeromycota in our study were non-random. We observed that space had a greater impact on fungal community structure than either time or proximity to Glomeromycota-associating trees but unlike host identity did not alter Glomeromycotan richness. The set of parameters which we addressed has rarely been studied together and we believe that the resulting ranking could ease prioritizing some of them to include in future surveys. Glomeromycota are crucial for the establishment of understory plants in temperate forests making it desirable to further explore how they vary in time and space.
Laminar dynamics of beta bursts in human motor cortex
Authors: Bonaiuto James J , Little Simon , Neymotin Samuel A , Jones Stephanie R , Barnes Gareth R , Bestmann Sven
Published: February 2021

Modulation of motor cortical activity in the beta frequency range is one of the strongest and most studied movement-related neural signals. At the single trial level, beta band activity is often characterized by transient bursting events rather than slowly modulating oscillations, suggesting a more rapid, information-encoding functional role than previously believed. Insight into how beta bursts are generated in sensorimotor circuits can provide important constraints to theories about their functional role for movement control. To this end, we leverage and extend recent developments in high precision MEG for temporally resolved laminar analysis of burst activity, combined with a neocortical circuit model that simulates the biophysical generators of the electrical currents which drive beta bursts. This approach pinpoints the generation of beta bursts in human motor cortex to distinct excitatory synaptic inputs to deep and superficial cortical layers, which drive current flow in opposite directions. These laminar dynamics of beta bursts in motor cortex align with prior invasive animal recordings within the somatosensory cortex, and suggest a conserved mechanism for somatosensory and motor cortical beta bursts. More generally, we demonstrate the ability for uncovering the laminar dynamics of event-related neural signals in human non-invasive recordings.
A dynamic view of histone tails interaction with clustered abasic sites in a nucleosome core particle
Authors: Bignon Emmanuelle , Gillet Natacha , Jiang Tao , Morell Christophe , Dumont Elise
Published: February 2021

Apurinic/apyrimidinic sites are the most common DNA damage under physiological conditions. Yet, their structural and dynamical behavior within nucleosome core particles has just begun to be investigated, and show dramatic differences with the one of abasic sites in B-DNA. Clusters of two or more abasic sites are repaired even less efficiently and hence constitute hotspots of high mutagenicity notably due to enhanced double-strand breaks formation. Based on a X-ray structure of a 146-bp DNA wrapped onto a histone core, we investigate the structural behavior of two bistranded abasic sites positioned at mutational hotspots along microsecond-range molecular dynamics simulations. Our simulations allow us to probe histone tails interactions at clustered abasic sites locations, with a definitive assignment of the key residues in-volved in the NCP-catalyzed formation of DNA–protein cross-linking in line with recent experimental findings, and pave the way towards a systematic assessment of histone tails response to DNA lesions.
Constitutive G protein coupling profiles of understudied orphan GPCRs
Authors: Lu Sumin , Jang Wonjo , Inoue Asuka , Lambert Nevin A.
Published: February 2021

A large number of GPCRs are potentially valuable drug targets but remain understudied. Many of these lack well-validated activating ligands and are considered “orphan” receptors, and G protein coupling profiles have not been defined for many orphan GPCRs. Here we asked if constitutive receptor activity can be used to determine G protein coupling profiles of orphan GPCRs. We monitored nucleotide-sensitive interactions between 48 understudied orphan GPCRs and five G proteins (240 combinations) using bioluminescence resonance energy transfer (BRET). No receptor ligands were used, but GDP was used as a common G protein ligand to disrupt receptor-G protein complexes. Constitutive BRET between the same receptors and β-arrestins was also measured. We found sufficient GDP-sensitive BRET to generate G protein coupling profiles for 22 of the 48 receptors we studied. Altogether we identified 48 coupled receptor-G protein pairs, many of which have not been described previously. We conclude that receptor-G protein complexes that form spontaneously in the absence of guanine nucleotides can be used to profile G protein coupling of constitutively active GPCRs. This approach may prove useful for studying G protein coupling of other GPCRs for which activating ligands are not available.
Frequent origins of traumatic insemination involve convergent shifts in sperm and genital morphology
Authors: Brand Jeremias N. , Harmon Luke J. , Schärer Lukas
Published: February 2021

Traumatic insemination is a mating behaviour during which the (sperm) donor uses a traumatic intromittent organ to inject an ejaculate through the epidermis of the (sperm) recipient, thereby frequently circumventing the female genitalia. Traumatic insemination occurs widely across animals, but the frequency of its evolution, the intermediate stages via which it originates, and the morphological changes that such shifts involve remain poorly understood. Based on observations in 145 species of the free-living flatworm genusMacrostomum, we identify at least nine independent evolutionary origins of traumatic insemination from reciprocal copulation, but no clear indication of reversals. These origins involve convergent shifts in multivariate morphospace of male and female reproductive traits, suggesting that traumatic insemination has a canalising effect on morphology. Signatures of male-female coevolution across the genus indicate that sexual selection and sexual conflict drive the evolution of traumatic insemination, because it allows donors to bypass postcopulatory control mechanisms of recipients.
Input–Output Slope Curve Estimation in Neural Stimulation Based on Optimal Sampling Principles
Authors: Mahdi Alavi Seyed Mohammad , Goetz Stefan M. , Saif Mehrdad
Published: February 2021

This paper discusses some of the practical limitations and issues, which exist for the input–output (IO) slope curve estimation (SCE) in neural, brain and spinal, stimulation techniques. The drawbacks of the SCE techniques by using existing uniform sampling and Fisher-information-based optimal IO curve estimation (FO-IOCE) methods are elaborated. A novel IO SCE technique is proposed with a modified sampling strategy and stopping rule which improve the SCE performance compared to these methods. The effectiveness of the proposed IO SCE is tested on 1000 simulation runs in transcranial magnetic stimulation (TMS), with a realistic model of motor evoked potentials (MEPs). The results show that the proposed IO SCE method successfully satisfies the stopping rule, before reaching the maximum number of TMS pulses in 79.5% of runs, while the estimation based on the uniform sampling technique never converges and satisfies the stopping rule. At the time of successful termination, the proposed IO SCE method decreases the 95th percentile (mean value in the parentheses) of the absolute relative estimation errors (AREs) of the slope curve parameters up to 7.45% (2.2%), with only 18 additional pulses on average compared to that of the FO-IOCE technique. It also decreases the 95th percentile (mean value in the parentheses) of the AREs of the IO slope curve parameters up to 59.33% (16.71%), compared to that of the uniform sampling method. The proposed IO SCE also identifies the peak slope with higher accuracy, with the 95th percentile (mean value in the parentheses) of AREs reduced by up to 9.96% (2.01%) compared to that of the FO-IOCE method, and by up to 46.29% (13.13%) compared to that of the uniform sampling method.
PAMP-triggered Genetic Reprogramming Involves Widespread Alternative Transcription Initiation and an Immediate Transcription Factor Wave
Authors: Thieffry Axel , Bornholdt Jette , Barghetti Andrea , Sandelin Albin , Brodersen Peter
Published: February 2021

Immune responses triggered by pathogen-associated molecular patterns (PAMPs) are key to pathogen defense, but drivers of the genetic reprogramming required to reach the immune state remain incompletely understood in plants. Here, we report a time-course study of the establishment of PAMP-triggered immunity (PTI) using cap analysis of gene expression (CAGE). Our results show that as much as 15% of all PAMP response genes display alternative transcription initiation. In several cases, use of alternative TSSs may be regulatory as it determines inclusion of target peptides or protein domains, or occurrence of upstream open reading frames (uORFs) in mRNA leader sequences. We also find that 60% of PAMP-response genes respond much earlier than previously thought. In particular, a previously unnoticed cluster of rapidly and transiently PAMP-induced genes is enriched in transcription factors whose functions, previously associated with biological processes as diverse as abiotic stress adaptation and stem cell activity, appear to converge on growth restriction. Furthermore, some examples of known potentiators of PTI, in one case under direct MAP kinase control, support the notion that the rapidly induced transcription factors could constitute direct links to PTI signaling pathways and drive gene expression changes underlying establishment of the immune state.
AGL16 negatively modulates stress response to balance with growth
Authors: Zhao Ping-Xia , Zhang Jing , Chen Si-Yan , Wu Jie , Xia Jing-Qiu , Sun Liang-Qi , Ma Shi-Song , Xiang Cheng-Bin
Published: February 2021

Sensile plants constantly experience environmental stresses in nature. They must have evolved effective mechanisms to balance growth with stress response. Here we report the MADS-box transcription factor AGL16 acting as a negative regulator in stress response. Loss-of-AGL16confers resistance to salt stress in seed germination, root elongation, and soil-grown plants, while elevatedAGL16expression confers the opposite phenotypes compared with wild type. However, the sensitivity to ABA in seed germination is inversely correlated withAGL16expression level. Transcriptomic comparison revealed that the improved salt resistance ofagl16mutant was largely attributed to enhanced expression of stress responsive transcriptional factors and genes involved in ABA signaling and ion homeostasis. We further demonstrated that AGL16 directly binds to the CArG motifs in the promoter ofHKT1;1,HsfA6a,andMYB102and represses their expression. Genetic analyses with double mutants also support thatHsfA6aandMYB102are target genes of AGL16. Taken together, our results show that AGL16 acts as negative regulator transcriptionally suppressing key components in stress response and may play a critical role in balancing stress response with growth.
Plant trait heterosis is quantitatively associated with expression heterosis of the plastid ribosomal proteins
Authors: Birdseye Devon , de Boer Laura A. , Bai Hua , Zhou Peng , Shen Zhouxin , Schmelz Eric A. , Springer Nathan M. , Briggs Steven P.
Published: February 2021

The use of hybrids is widespread in agriculture, yet the molecular basis for hybrid vigor (heterosis) remains obscure. To identify molecular components that may contribute to the known higher photosynthetic capacity of maize hybrids, we analyzed proteomic and transcriptomic data from seedling leaf tissues of the hybrid, B73×Mo17, and its inbred parents. Subunits of complexes required for protein synthesis in the chloroplast and for the light reactions of photosynthesis were expressed above mid-parent and high-parent levels, respectively. Nuclear and plastid-encoded subunits were expressed similarly and in a dominant pattern with B73 as the high-parent for most proteins. The reciprocal hybrid displayed the same pattern with B73 still the dominant parent. Protein expression patterns were mostly the same in the adult leaf blade. To rank the relevance of expression differences to trait heterosis, we compared seedling leaf protein levels to adult plant heights of 15 hybrids. Expression heterosis (hybrid/mid-parent expression levels) was most positively correlated with plant height heterosis (hybrid/mid-parent plant height) for the plastid-encoded and nuclear-encoded chloroplast ribosomal proteins; the cytosolic ribosomal proteins were slightly less correlated. Ethylene biosynthetic enzymes were expressed below mid-parent levels in the hybrids, and the ethylene biosynthesis mutant,acs2/acs6, largely phenocopied the hybrid proteome, indicating that a reduction in ethylene biosynthesis may mediate the differences between inbreds and their hybrids. Levels of jasmonic acid biosynthetic enzymes were reduced in bothacs2/acs6and the hybrid, and expression heterosis levels of these proteins were the most negatively correlated with plant height heterosis.

Significance Statement

Heterosis (hybrid vigor) boosts the productivity and resilience of crops and livestock above the levels of both parents, yet its underlying mechanisms remain unknown. We analyzed expression patterns of proteins in maize hybrids and their inbred parents. Differences in several molecular machines and biochemical pathways were found and quantitatively assessed using a panel of 15 hybrids. Seedling leaf chloroplast ribosomal proteins were able to quantitatively infer levels of adult plant heterosis. Expression levels of biosynthetic enzymes for the stress hormone, ethylene, were reduced in hybrids as was previously reported for the dicot Arabidopsis. Mutation of these genes in a maize inbred caused the proteome to resemble a hybrid. Repression of ethylene biosynthesis may be a conserved component of heterosis physiology.