bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural insights into the activation of human calcium-sensing receptor
Authors: Chen Xiaochen , Wang Lu , Ding Zhanyu , Cui Qianqian , Han Li , Kou Yongjun , Zhang Wenqing , Wang Haonan , Jia Xiaomin , Dai Mei , Shi Zhenzhong , Li Yuying , Li Xiyang , Geng Yong
Published: March 2021

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that maintains Ca2+homeostasis in serum. Here, we present the cryo-electron microscopy structures of the CaSR in the inactive and active states. Complemented with previously reported crystal structures of CaSR extracellular domains, it suggests that there are three distinct conformations: inactive, intermediate and active state during the activation. We used a negative allosteric nanobody to stabilize the CaSR in the fully inactive state and found a new binding site for Ca2+ion that acts as a composite agonist with L-amino acid to stabilize the closure of active Venus flytraps. Our data shows that the agonist binding leads to the compaction of the dimer, the proximity of the cysteine-rich domains, the large-scale transitions of 7-transmembrane domains, and the inter-and intrasubunit conformational changes of 7-transmembrane domains to accommodate the downstream transducers. Our results reveal the structural basis for activation mechanisms of the CaSR.
Acclimation ofChlamydomonas reinhardtiito Nitric Oxide Stress Related to Respiratory Burst Oxidase-Like 2
Authors: Kuo Eva YuHua , Lee Tse-Min
Published: March 2021

The acclimation mechanism ofChlamydomonas reinhardtiito nitric oxide (NO) was studied by exposure toS-nitroso-N-acetylpenicillamine (SNAP), a NO donor. Treatment with 0.1 or 0.3 mM SNAP transiently inhibited photosynthesis within 1 h, followed by a recovery without growth impairment, while 1.0 mM SNAP treatment caused irreversible photosynthesis inhibition and mortality. The SNAP effects are avoided in the presence of the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide (cPTIO). RNA-seq, qPCR, and biochemical analyses were conducted to decode the metabolic shifts under sub-lethal NO stress by exposure to 0.3 mM SNAP in the presence or absence of 0.4 mM cPTIO. These findings revealed that the acclimation to NO stress comprises a temporally orchestrated implementation of metabolic processes: 1. trigger of NO scavenging elements to reduce NO level; 2. prevention of photo-oxidative risk through photosynthesis inhibition and antioxidant defense system induction; 3. acclimation to nitrogen and sulfur shortage; 4. degradation of damaged proteins through protein trafficking machinery (ubiquitin, SNARE, and autophagy) and molecular chaperone system for dynamic regulation of protein homeostasis. NO increased NADPH oxidase activity and respiratory burst oxidase-like 2 (RBOL2) transcript abundance, which were not observed in therbol2insertion mutant. Changes in gene expression in therbol2mutant and increased mortality under NO stress demonstrate that NADPH oxidase (RBOL2) is involved in the modulation of some acclimation processes (NO scavenging, antioxidant defense system, autophagy, and heat shock proteins) forChlamydomonasto cope with NO stress. Our findings provide insight into the molecular events underlying acclimation mechanisms inChlamydomonasto sub-lethal NO stress.

One-sentence Summary

Acclimation machinery is triggered inChlamydomonas reinhardtiicells against sub-lethal nitric oxide stress.
Supramolecular cylinders target bulge structures in the 5’ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication
Authors: Melidis Lazaros , Hill Harriet J. , Coltman Nicholas J. , Davies Scott P. , Winczura Kinga , Chauhan Tasha , Craig James S. , Garai Aditya , Hooper Catherine A..J. , Egan Ross T. , McKeating Jane A. , Hodges Nikolas J. , Stamataki Zania , Grzechnik Pawel , Hannon Michael J.
Published: March 2021

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with Molecular Dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5’ UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in the stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel antiviral agents.
Structural characterization of the antimicrobial peptides myxinidin and WMR in bacterial membrane mimetic micelles and bicelles
Authors: Cherniavskyi Yevhen K. , Oliva Rosario , Stellato Marco , Vecchio Pompea Del , Galdiero Stefania , Falanga Annarita , Dames Sonja A. , Tieleman D. Peter
Published: March 2021

Antimicrobial peptides are a promising class of alternative antibiotics that interact selectively with negatively charged lipid bilayers. This paper presents the structural characterization of the antimicrobial peptides myxinidin and WMR associated with bacterial membrane mimetic micelles and bicelles by NMR, CD spectroscopy, and Molecular Dynamics simulations. Both peptides adopt a different conformation in the lipidic environment than in aqueous solution. The location of peptides in micelles and bicelles has been studied by paramagnetic relaxation enhancement experiments with paramagnetic tagged 5- and 16-doxyl stearic acid (5-/16-SASL). Multi-microsecond long molecular dynamics simulations of multiple copies of the peptides were used to gain an atomic level of detail on membrane-peptide and peptide-peptide interactions. Our results highlight an essential role of the negatively charged membrane mimetic in the structural stability of both myxinidin and WMR. The peptides localize predominantly in the membrane’s headgroup region and have a noticeable membrane thinning effect on the overall bilayer structure. Myxinidin and WMR show different tendency to selfaggregate, which is also influenced by the membrane composition (DOPE/DOPG versus DOPE/DOPG/CL) and can be related to the previously observed difference in the ability of the peptides to disrupt different types of model membranes.
A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection
Authors: Zhou Panpan , Yuan Meng , Song Ge , Beutler Nathan , Shaabani Namir , Huang Deli , He Wan-ting , Zhu Xueyong , Callaghan Sean , Yong Peter , Anzanello Fabio , Peng Linghang , Ricketts James , Parren Mara , Garcia Elijah , Rawlings Stephen A. , Smith Davey M. , Nemazee David , Teijaro John R. , Rogers Thomas F. , Wilson Ian A. , Burton Dennis R. , Andrabi Raiees
Published: March 2021

Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and, importantly, as templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from a coronavirus disease 2019 (COVID-19)-convalescent donor that exhibits broad reactivity with human beta-coronaviruses (β-CoVs). Here, we showed that CC40.8 targets the conserved S2 stem-helix region of the coronavirus spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem-peptide at 1.6 Å resolution and found that the peptide adopted a mainly helical structure. Conserved residues in β-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. Furthermore, we noted CC40.8-like bnAbs are relatively rare in human COVID-19 infection and therefore their elicitation may require rational structure-based vaccine design strategies. Overall, our study describes a target on β-CoV spike proteins for protective antibodies that may facilitate the development of pan-β-CoV vaccines.

A human mAb isolated from a COVID-19 donor defines a protective cross-neutralizing epitope for pan-β-CoV vaccine design strategies
Cellular variability of nonsense-mediated mRNA decay
Authors: Sato Hanae , Singer Robert H.
Published: March 2021

Nonsense-mediated mRNA decay (NMD) is an mRNA degradation pathway that eliminates transcripts containing premature termination codons (PTCs). Half-lives of the mRNAs containing PTCs demonstrate that a small percent escape surveillance and do not degrade. It is not known whether this escape represents variable mRNA degradation within cells or, alternatively cells within the population are resistant. Here we demonstrate a single-cell approach with a bi-directional reporter, which expresses two β-globin genes with or without a PTC in the same cell, to characterize the efficiency of NMD in individual cells. We found a broad range of NMD efficiency in the population; some cells degraded essentially all of the mRNAs, while others escaped NMD almost completely. Characterization of NMD efficiency together with NMD regulators in single cells showed cell-to-cell variability of NMD reflects the differential level of surveillance factors, SMG1 and phosphorylated UPF1. A single-cell fluorescent reporter system that enabled detection of NMD using flow cytometry revealed that this escape occurred either by translational readthrough at the PTC or by a failure of mRNA degradation after successful translation termination at the PTC.
Memory specific to temporal features of sound is formed by cue-selective enhancements in temporal coding enabled by inhibition of an epigenetic regulator
Authors: Rotondo Elena K. , Bieszczad Kasia M.
Published: March 2021

Recent investigation of memory-related functions in the auditory system have capitalized on the use of memory-modulating molecules to probe the relationship between memory and its substrates in auditory system coding. For example, epigenetic mechanisms, which regulate gene expression necessary for memory consolidation, are powerful modulators of learning-induced neuroplasticity and long-term memory formation (LTM). Inhibition of the epigenetic regulator histone deacetylase 3 (HDAC3) promotes LTM that is highly specific forspectralfeatures of sound. The present work demonstrates for the first time that HDAC3 inhibition also enables memory fortemporalfeatures of sound. Rats trained in an amplitude modulation (AM) rate discrimination task and treated with a selective inhibitor of HDAC3 formed memory that was unusually specific to the AM rate paired with reward. Unusually sound-specific memory revealed behaviorally was associated with a signal-specific enhancement in temporal coding in the auditory system: stronger phase-locking that was specific to the rewarded AM rate was revealed in both the surface-recorded frequency following response (FFR) and auditory cortical multiunit activity in rats treated with the HDAC3-inhibitor. Furthermore, HDAC3inhibition increased trial-to-trial cortical response consistency (relative to naïve and trained vehicle-treated rats) that generalized across different AM rates. Stronger signal-specific phase-locking correlated with individual behavioral differences in memory specificity for the AM signal. Together, these findings support that epigenetic mechanisms regulate activity-dependent processes that enhance discriminability of sensory cues encoded into LTM in both spectral and temporal domains, which may be important for remembering spectrotemporal features of sounds, e.g., as in human voices and speech.

SIGNIFICANCE STATEMENT

Epigenetic mechanisms have recently been implicated in memory and information processing. Here, we use a pharmacological inhibitor of histone deacetylase 3 (HDAC3) in a sensory model of learning to reveal, for the first time, its ability to enable unusually precise memory for amplitude modulated sound cues. In so doing, we uncover neural substrates for memory’s “specificity” for temporal sound cues. Memory specificity was supported by auditory cortical changes in temporal coding, including greater response consistency and stronger phase-locking. HDAC3 appears to regulate effects across domains that determine specific cue saliency for behavior. Thus, epigenetic players may gate how sensory information is stored in long-term memory and can be leveraged to reveal the neural substrates of sensory details stored in memory.
A flash-based thermal simulation of scanning paths in LPBF additive manufacturing
Authors: Ettaieb Kamel , Lavernhe Sylvain , Tournier Christophe
Published: March 2021

Purpose

This paper aims to propose an analytical thermal three-dimensional model that allows an efficient evaluation of the thermal effect of the laser-scanning path. During manufacturing by laser powder bed fusion (LPBF), the laser-scanning path influences the thermo-mechanical behavior of parts. Therefore, it is necessary to validate the path generation considering the thermal behavior induced by this process to improve the quality of parts.

Design/methodology/approach

The proposed model, based on the effect of successive thermal flashes along the scanning path, is calibrated and validated by comparison with thermal results obtained by FEM software and experimental measurements. A numerical investigation is performed to compare different scanning path strategies on the Ti6Al4V material with different stimulation parameters.

Findings

The simulation results confirm the effectiveness of the approach to simulate the thermal field to validate the scanning strategy. It suggests a change in the scale of simulation thanks to high-performance computing resources.

Originality/value

The flash-based approach is designed to ensure the quality of the simulated thermal field while minimizing the computational cost.
Amazonian mammal monitoring using aquatic environmental DNA
Authors: Coutant Opale , Richard‐Hansen Cécile , de Thoisy Benoit , Decotte Jean‐Baptiste , Valentini Alice , Dejean Tony , Vigouroux Régis , Murienne Jérôme , Brosse Sébastien
Published: March 2021

Environmental DNA (eDNA) metabarcoding has emerged as one of the most efficient methods to assess aquatic species presence. While the method can in theory be used to investigate nonaquatic fauna, its development for inventorying semi‐aquatic and terrestrial fauna is still at an early stage. Here we investigated the potential of aquatic eDNA metabarcoding for inventorying mammals in Neotropical environments, be they aquatic, semi‐aquatic or terrestrial. We collected aquatic eDNA in 96 sites distributed along three Guianese watersheds and compared our inventories to expected species distributions and field observations derived from line transects located throughout French Guiana. Species occurrences and emblematic mammalian fauna richness patterns were consistent with the expected distribution of fauna and our results revealed that aquatic eDNA metabarcoding brings additional data to line transect samples for diurnal nonaquatic (terrestrial and arboreal) species. Aquatic eDNA also provided data on species not detectable in line transect surveys such as semi‐aquatic, aquatic and nocturnal terrestrial and arboreal species. Although the application of eDNA to inventory mammals still needs some developments to optimize sampling efficiency, it can now be used as a complement to traditional surveys.
“Protein aggregates” contain RNA and DNA, entrapped by misfolded proteins but largely rescued by slowing translational elongation
Authors: Shmookler Reis Robert J. , Atluri Ramani , Balasubramaniam Meenakshisundaram , Johnson Jay , Ganne Akshatha , Ayyadevara Srinivas
Published: March 2021

All neurodegenerative diseases feature aggregates, which usually contain disease‐specific diagnostic proteins; non‐protein constituents, however, have rarely been explored. Aggregates from SY5Y‐APPSw neuroblastoma, a cell model of familial Alzheimer's disease, were crosslinked and sequences of linked peptides identified. We constructed a normalized “contactome” comprising 11 subnetworks, centered on 24 high‐connectivity hubs. Remarkably, all 24 are nucleic acid‐binding proteins. This led us to isolate and sequence RNA and DNA from Alzheimer's and control aggregates. RNA fragments were mapped to the human genome by RNA‐seq and DNA by ChIP‐seq. Nearly all aggregate RNA sequences mapped to specific genes, whereas DNA fragments were predominantly intergenic. These nucleic acid mappings are all significantly nonrandom, making an artifactual origin extremely unlikely. RNA (mostly cytoplasmic) exceeded DNA (chiefly nuclear) by twofold to fivefold. RNA fragments recovered from AD tissue were ~1.5‐to 2.5‐fold more abundant than those recovered from control tissue, similar to the increase in protein. Aggregate abundances of specific RNA sequences were strikingly differential between cultured SY5Y‐APPSw glioblastoma cells expressing APOE3 vs. APOE4, consistent with APOE4 competition for E‐box/CLEAR motifs. We identified many G‐quadruplex and viral sequences within RNA and DNA of aggregates, suggesting that sequestration of viral genomes may have driven the evolution of disordered nucleic acid‐binding proteins. After RNA‐interference knockdown of the translational‐procession factor EEF2 to suppress translation in SY5Y‐APPSw cells, the RNA content of aggregates declined by >90%, while reducing protein content by only 30% and altering DNA content by ≤10%. This implies that cotranslational misfolding of nascent proteins may ensnare polysomes into aggregates, accounting for most of their RNA content.
The correlates and extent of prescribing of medications for alcohol relapse prevention in England
Authors: Donoghue Kim
Published: March 2021

Aims

To determine the pattern and extent of prescribing of medications for alcohol relapse prevention (ARP) in England.

Design

Cross‐sectional.

Setting

Specialist drug and alcohol treatment providers in England reporting to the National Drug Treatment Monitoring System.

Participants

Service users aged 18+, with alcohol the primary substance of dependence, completing a treatment journey between April 2013 and March 2016 (n = 188 152).

Measurements

Prescription of medications for ARP during a treatment journey. Data on service users’ demographics, treatment and clinical characteristics were extracted.

Findings

The rate of prescribing medications for ARP was 2.1% in 2013/14, 6.8% in 2014/15 and 7.8% in 2015/16. A greater likelihood of prescription was associated with treatment journey year [2014/15; adjusted odds ratio (aOR) = 3.269, 95% confidence intervals (CI) = 3.044–3.510, 2015/16; aOR = 3.823, CI = 3.560–4.106], age (25–34; aOR = 1.622, CI = 1.380–1.907, 35–54; aOR = 1.901, CI = 1.628–2.220 or 55+; aOR = 1.700, CI = 1.446–1.999), female gender (aOR = 1.129, CI = 1.077–1.184), white ethnicity (aOR = 1.219, CI = 1.077–1.380), regional prevalence of alcohol dependence (middle rate; aOR = 1.121, CI = 1.024–1.228), severity of alcohol dependence (moderate dependence without complex needs; aOR = 1.329, CI = 1.244–1.419, severe dependence without complex needs; aOR = 1.308, CI = 1.188–1.441, moderate/severe dependence with complex needs; aOR = 1.131, CI = 1.020–1.255), treatment setting (inpatient; aOR = 10.512, CI = 9.950–11.104, primary care; aOR = 2.264, CI = 2.050–2.500, residential; aOR = 3.216, CI = 2.807–3.685), prior treatment for alcohol dependence (aOR = 1.242, CI = 1.183–1.304), longer treatment journey (aOR = 1.002, CI = 1.002–1.002), more drinking days in the prior 28 days (aOR = 1.021, CI = 1.018–1.024) and drinking a higher number of alcohol units in the prior 28 days (aOR = 1.002 CI = 1.001–1.004). Living in a region of England with the lowest alcohol prevalence was associated with a lower likelihood of prescription of medication for aRP (AOR = 0.491, CI = 0.436–0.552).

Conclusions

In England, medications for alcohol relapse prevention are rarely prescribed (e.g. 7.8% in 2015/16) and those prescriptions appear to be associated with specific service user demographics, treatment and clinical characteristics.
What do older people want from integrated care? Experiences from a South Australian co‐design case study
Authors: Marshall Amy , Rawlings Kirsty , Zaluski Sharmilla , Gonzalez Pablo , Harvey Gill
Published: March 2021

Objectives

The challenges of improving the integration of care for older people with complex care needs are well recognised. Evidence suggests that solutions should be co‐designed with older people to ensure they are contextually relevant and person‐centred.

Methods

As a first step in a co‐design project to improve integrated care for older people, seven interviews and three workshops were held with older people and service providers. Data collected via recordings, notes and journey maps were inductively analysed.

Results

Five themes were identified: relationships and roles, patient capacity and safety, information and systems, multiway communication, and transitions and flow. This created a more holistic and person‐centred picture of integrated care than typically derived from published literature.

Conclusions

Older people perceive integrated care from relational, organisational, informational and individual viewpoints. This reinforces the central importance of adopting a person‐centred, as opposed to health system‐focused, approach to designing and implementing integrated care solutions.
A Shared‐Cost‐Profit Model of Teaching Materials for Higher Education
Authors: Banfield Melanie
Published: March 2021

In this article, I assess the cost‐value crisis facing institutions of higher education; as the cost of higher education grows, students grow increasingly skeptical of the value of their degrees. The COVID‐19 pandemic has accelerated this crisis as institutions across the country have been forced to move to a fully or partially online model of instruction. In an effort to reduce costs, institutions have increased the number of low‐paid, part‐time adjunct faculty teaching introductory courses and have promoted the use of free and open online educational resources (OER). Both solutions lack sustainability and do little to solve the “value” question of higher education. I demonstrate how a shared‐cost‐profit model could address both issues of sustainability and value.
Dynamic interplay between cell membrane tension and clathrin‐mediated endocytosis
Authors: Djakbarova Umidahan , Madraki Yasaman , Chan Emily T. , Kural Cömert
Published: March 2021

Deformability of the plasma membrane, the outermost surface of metazoan cells, allows cells to be dynamic, mobile and flexible. Factors that affect this deformability, such as tension on the membrane, can regulate a myriad of cellular functions, including membrane resealing, cell motility, polarisation, shape maintenance, membrane area control and endocytic vesicle trafficking. This review focuses on mechanoregulation of clathrin‐mediated endocytosis (CME). We first delineate the origins of cell membrane tension and the factors that yield to its spatial and temporal fluctuations within cells. We then review the recent literature demonstrating that tension on the membrane is a fast‐acting and reversible regulator of CME. Finally, we discuss tension‐based regulation of endocytic clathrin coat formation during physiological processes.
In vitro safety “clinical trial” of the cardiac liability of drug polytherapy
Authors: Charrez Bérénice , Charwat Verena , Siemons Brian , Finsberg Henrik , Miller Evan W. , Edwards Andrew G. , Healy Kevin E.
Published: March 2021

Only a handful of US Food and Drug Administration (FDA) Emergency Use Authorizations exist for drug and biologic therapeutics that treat severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. Potential therapeutics include repurposed drugs, some with cardiac liabilities. We report on a chronic preclinical drug screening platform, a cardiac microphysiological system (MPS), to assess cardiotoxicity associated with repurposed hydroxychloroquine (HCQ) and azithromycin (AZM) polytherapy in a mock phase I safety clinical trial. The MPS contained human heart muscle derived from induced pluripotent stem cells. The effect of drug response was measured using outputs that correlate with clinical measurements, such as QT interval (action potential duration) and drug‐biomarker pairing. Chronic exposure (10 days) of heart muscle to HCQ alone elicited early afterdepolarizations and increased QT interval past 5 days. AZM alone elicited an increase in QT interval from day 7 onward, and arrhythmias were observed at days 8 and 10. Monotherapy results mimicked clinical trial outcomes. Upon chronic exposure to HCQ and AZM polytherapy, we observed an increase in QT interval on days 4–8. Interestingly, a decrease in arrhythmias and instabilities was observed in polytherapy relative to monotherapy, in concordance with published clinical trials. Biomarkers, most of them measurable in patients’ serum, were identified for negative effects of monotherapy or polytherapy on tissue contractile function, morphology, and antioxidant protection. The cardiac MPS correctly predicted clinical arrhythmias associated with QT prolongation and rhythm instabilities. This high content system can help clinicians design their trials, rapidly project cardiac outcomes, and define new monitoring biomarkers to accelerate access of patients to safe coronavirus disease 2019 (COVID‐19) therapeutics.
Role of triggering receptor expressed on myeloid cells 2 (TREM2) in neurodegenerative dementias
Authors: Shafi Sadat , Singh Archu , Ibrahim Abdallah Mohammad , Alhajri Noora , Abu Izneid Tareq , Pottoo Faheem Hyder
Published: March 2021

Neurodegeneration is a debilitating condition that causes nerve cell degeneration or death. Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and Lewy body dementia (LBD) are posing a larger population burden of dementia worldwide. Neurodegenerative dementia is one of the main challenges in public health with its main characteristics being permanent loss of memory, impairment in cognition, and impaired daily functions. The published literature about genetic studies of these disorders suggests genetic underpinning in the pathogenesis of neurodegenerative dementia. In the process of underlining the pathogenesis of NDD, growing evidence has related genetic variations in the triggering receptor expressed on myeloid cells 2 (TREM2). This review paper aims to provide a detailed information regarding the association of TREM2 and NDDs leading to dementia. A central consideration is AD that accounts for almost 50%–70% of all late‐life dementias alone or in combination with other neurological disorders. Other prevalent neurodegenerative conditions that lead to dementia are also discussed. Such studies are important as they can give a comprehensive knowledge of TREM2's role in various NDDs, in order to maximize the potential for developing new therapeutic approaches.
Anxiety‐related defensive behavioral responses in mice selectively bred for High and Low Activity
Authors: Booher Winona C. , Hall Lucy A. , Thomas Aimee L. , Merhroff Erika A. , Reyes Martínez Guillermo J. , Scanlon Katharine E. , Lowry Christopher A. , Ehringer Marissa A.
Published: March 2021

High and Low Activity strains of mice (displaying low and high anxiety‐like behavior, respectively) with 7.8–20 fold differences in open‐field activity were selected and subsequently inbred to use as a genetic model for studying anxiety‐like behavior in mice (DeFries et al., 1978, Behavior Genetics, 8:3‐13). These strains exhibited differences in other anxiety‐related behaviors as assessed using the light–dark box, elevated plus‐maze, mirror chamber, and elevated square‐maze tests (Henderson et al., 2004, Behavior Genetics, 34: 267‐293). The purpose of these experiments was three‐fold. First, we repeated a 6‐day behavioral battery using updated equipment and software to confirm the extreme differences in anxiety‐like behaviors. Second, we tested novel object exploration, a measure of anxiety‐like behavior that does not rely heavily on locomotion. Third, we conducted a home cage wheel running experiment to determine whether these strains differ in locomotor activity in a familiar, home cage environment. Our behavioral test battery confirmed extreme differences in multiple measures of anxiety‐like behaviors. Furthermore, the novel object test demonstrated that the High Activity mice exhibited decreased anxiety‐like behaviors (increased nose pokes) compared to Low Activity mice. Finally, male Low Activity mice ran nearly twice as far each day on running wheels compared to High Activity mice, while female High and Low Activity mice did not differ in wheel running. These results support the idea that the behavioral differences between High and Low Activity mice are likely to be due to anxiety‐related factors and not simply generalized differences in locomotor activity.
Documentation by citizen scientists/naturalists of the ‘Cambrian explosion’ in Pennsylvania
Authors: Thomas Roger D. K.
Published: March 2021

For more than 125 years, teachers and amateur naturalists have sought early Cambrian fossils, emerging from scattered, unimpressive outcrops of shale in southeastern Pennsylvania. Prizing their finds, they have regularly made their most scientifically significant specimens available to professionals for study and incorporation into museum collections. This activity has played a key part in establishing the fauna of the Kinzers Formation as an important record of the early Cambrian diversification of marine life. Today, a new generation of collectors is building on this tradition, continuing to discover new and evolutionarily significant fossils.
A review on biological interactions and management of the cotton bollworm,Helicoverpa armigera(Lepidoptera: Noctuidae)
Authors: Riaz Shahzab , Johnson Joel B. , Ahmad Munir , Fitt Gary P. , Naiker Mani
Published: March 2021

Helicoverpa armigeraHübner (Lepidoptera: Noctuidae) is one of the most damaging insect pests globally, causing estimated global economic losses of over 3 billion US dollars annually. Crops most affected include cotton, tomato, soybean, grain crops such as corn and sorghum, chickpea and other pulses. Adults of this species possess strong migratory abilities (>2000 km), high fecundity and rapid reproductive rates; completing 4–6 generations per year in most cropping regions. Furthermore, the larvae are polyphagous, with a wide and diverse host range and possess the ability to enter diapause in order to survive adverse climatic conditions. At present, it is distributed across most of Oceania, Asia, Africa and southern Europe and has recently spread to South America. Various control measures have been trialled or proposed for the treatment of this pest, including synthetic insecticides, phytopesticides, microbial pesticides, macro‐biocontrol agents (both parasitoids and predators) and the development of genetically modified crops (e.g.Btcotton). Successful control necessitates the use of an integrated pest management (IPM) approach, wherein biological, chemical and physical control measures are combined for the greatest control efficacy.
Predicting sun protection measures against skin diseases using machine learning approaches
Authors: Sultana Nahid
Published: March 2021

Background

The substantial growth rate of skin cancer has necessitated adequate protection from solar radiation. Consequently, analyzing sun protection practices is an imperative research area in dermatology and pharmacology.

Aims

This paper aims to analyze public sun‐protection manners in the Arabian Peninsula regions.

Methods

A simple random survey was conducted to assess public sun protection manners. Artificial neural network (ANN) and support vector machine (SVM) were selected from several machine learning algorithms to create the models for predicting public sun protection measures based on the prediction accuracy. Model performances were evaluated based on several performance indicators depending on the confusion matrices and receiver operating characteristic curves.

Results

51% of the respondents have a low level, and 49% have a high level of sun protection practices. The results showed that the SVM performed considerably amended than the ANN for predicting the response. The relative importance of the predictors for the best predictive SVM model was also analyzed. The predictors are ranked as: the number of times having sunburnt >gender > use seat belt while driving/riding a vehicle >considers the UV index for personal sun exposure >income based on the expenses >sports/exercise activities >consciousness of the chance for having sunburnt on extended exposure to the sun >age > having any skin problem >nationality > skin type.

Conclusion

These identified significant predictors might be considered for developing an effective policy to increase public consciousness using proper protection from solar radiation's detrimental effect to rule out skin diseases.
Self‐Perceptions, Normative Beliefs, and Substance Use Associated With High School Girls Comparing Themselves to Peers
Authors: Merianos Ashley L. , Mahabee‐Gittens E. Melinda , Jacobs Wura , Oloruntoba Oluyomi , Barry Adam E. , Smith Matthew Lee
Published: March 2021

BACKGROUND

We assessed whether self‐descriptions, self‐perceptions, perceived substance use of friends, and actual substance use were associated with high school girls' frequency of making social comparisons to peers.

METHODS

We analyzed data from the Adolescent Health Risk Behavior Survey data for 357 high school girls using multinomial logistic regression.

RESULTS

Compared to those who “never/rarely” made social comparisons, participants who self‐described as fearing something constantly (p = .014) and forced to imitate the people they like (p = .009) were more likely to “usually” compare themselves to peers. Participants who described themselves as feeling forced to imitate the people they like (p = .022), were not the person they would like to be (p = .005), and did not remain calm under pressure (p = .010), were more likely to “often/always” make social comparisons. Participants who perceived themselves as unattractive (p = .034) and self‐centered (p = .016) were more likely to “often/always” make social comparisons. Participants who perceived a larger proportion of friends use illicit drugs were less likely to “usually” make social comparisons (p = .027). Participants who perceived a larger proportion of friends drink alcohol were more likely to “often/always” make social comparisons (p = .018).

CONCLUSIONS

Girls who perceive and describe themselves more negatively are at increased odds of making social comparisons to peers.
The MSP‐RON pathway regulates liver fibrosis through transforming growth factor beta‐dependent epithelial–mesenchymal transition
Authors: Weng Tianhao , Yan Dong , Shi Danrong , Zhu Miaojin , Liu Yizhi , Wu Zhigang , Tang Taoming , Zhu Linwei , Zhang Hong , Yao Hangping , Li Lanjuan
Published: March 2021

Background

Liver fibrosis is pathologically important in the liver cirrhosis progression. The epithelial–mesenchymal transition (EMT) is crucial for organ fibrosis. Macrophage‐stimulating protein (MSP) and its receptor tyrosine kinase, RON, promote cellular EMT. However, their role in liver fibrosis is unclear. Here, we clarify the biological profile, potential mechanisms and therapeutic targets of the MSP‐RON pathway in liver fibrosis.

Materials and methods

Macrophage‐stimulating protein expression and its correlation with clinicopathological characteristics of cirrhosis were evaluated in 57 clinical cases and a control group. The effect of MSP‐RON pathway in liver fibrosis was determined in vitro and in vivo. The therapeutic effects of MSP or RON inhibition on liver fibrosis were evaluated in a mouse liver fibrosis model.

Results

Macrophage‐stimulating protein is upregulated in liver cirrhosis, which was associated with poor patient prognosis. The MSP‐RON pathway promoted hepatocytes EMT. MSP‐RON‐induced EMT depends on the transforming growth factor beta (TGF‐β) pathway and is regulated by TGF‐β inhibitors. In animal models, an MSP blocking antibody and a small molecule inhibitor of RON, BMS‐777607, both inhibited liver fibrosis progression.

Conclusion

Our study revealed that MSP is an important biomarker in liver cirrhosis progression and can be used to prognose patients. The MSP‐RON pathway promotes the EMT of hepatocytes and the progress of fibrosis via a TGF‐β related pathway. Consequently, we identified a new treatment strategy for liver cirrhosis through targeted inhibition of MSP/RON. This research increases the understanding of EMT‐modulated liver fibrosis and provides new insights into biomarkers and therapeutic targets of liver fibrosis.
The virus–host interface: Molecular interactions of Alphacoronavirus‐1 variants from wild and domestic hosts with mammalian aminopeptidase N
Authors: Olarte‐Castillo Ximena A. , dos Remédios Joana F. , Heeger Felix , Hofer Heribert , Karl Stephan , Greenwood Alex D. , East Marion L.
Published: March 2021

The Alphacoronavirus‐1 species include viruses that infect numerous mammalian species. To better understand the wide host range of these viruses, better knowledge on the molecular determinants of virus–host cell entry mechanisms in wildlife hosts is essential. We investigated Alphacoronavirus‐1 infection in carnivores using long‐term data on Serengeti spotted hyenas (Crocuta crocuta) and molecular analyses guided by the tertiary structure of the viral spike (S) attachment protein's interface with the host receptor aminopeptidase N (APN). We sequenced the complete 3′‐end region of the genome of nine variants from wild African carnivores, plus the APN gene of 15 wild carnivore species. Our results revealed two outbreaks of Alphacoronavirus‐1 infection in spotted hyenas associated with genetically distinct canine coronavirus type II (CCoVII) variants. Within the receptor binding domain (RBD) of the S gene the residues that directly bind to the APN receptor were conserved in all variants studied, even those infecting phylogenetically diverse host taxa. We identified a variable region within RBD located next to a region that directly interacts with the APN receptor. Two residues within this variable region were under positive selection in hyena variants, indicating that both sites were associated with adaptation of CCoVII to spotted hyena APN. Analysis of APN sequences revealed that most residues that interact with the S protein are conserved in wild carnivores, whereas some adjacent residues are highly variable. Of the variable residues, four that are critical for virus–host binding were under positive selection and may modulate the efficiency of virus attachment to carnivore APN.
CoNPR1 and CoNPR3.1 are involved in SA‐ and MeSA‐ mediated growth of the pollen tube in Camellia oleifera
Authors: Lu Mengqi , Zhou Junqin , Liu Yiyao , Yang Jin , Tan Xiaofeng
Published: March 2021

Salicylic acid (SA) is a plant hormone involved in a series of growth, development, and stress responses in plants. Nonexpressor of pathogenesis‐related genes 1 (NPR1) is the core regulatory gene in the process of SA‐mediated systemic acquired resistance (SAR). Whether NPR1 is involved in pollen tube growth mediated by SA and its derivative MeSA (methyl salicylate) remains to be explored. Here, we found that the contents of endogenous SA and MeSA in self‐ or cross‐pollinated pistils changed significantly, and exogenous SA and MeSA significantly promoted pollen germination and pollen tube elongation of Camellia oleifera at lower concentrations. CoNPR1, CoNPR3.1, CoNPR3.2, and CoNPR5 were identified, and they were all located in the nucleus. A high level of consistency was observed across the phylogenetic relationships, gene structures, and functional domains, indicating a clear division of function, as observed in other species. The expression levels of CoNPR1, CoNPR3.1, CoNPR3.2, and CoNPR5 in self‐ and cross‐pollinated pistils had certain regularity. Furthermore, they exhibited tissue‐specific expression pattern. CoNPR1 and CoNPR3.1 were expressed in pollen tubes, whose expression was regulated by SA or MeSA, and their expression patterns were basically consistent with the trend of pollen germination. These results indicate that SA and MeSA are involved in the pollen tube growth of C. oleifera, and CoNPRs may play an important role therein.
Acknowledging the historical contributions of Black Youth's civic engagement in society
Authors: Webster Nicole
Published: March 2021

Historical contributions of Black youth voices and actions are overlooked from many of the narratives of youth civic engagement (YCE) literature. Specifically, the histories and stories of African American youth in the United States and Black Caribbean youth in the Anglophone Caribbean. The shared socio and political obstacles these particular groups have encountered throughout history shaped similar paths for their involvement in civic society to address many of these social and racial injustices. The article's premise centers on the need for the YCE literature to acknowledge the historical civic contributions African American and Black Caribbean youth have made throughout history. Fundamental historical civic movements that were designed, developed, and supported by Black youth set the tone of Black youth's civic engagement throughout history. These were shaped and contextualized by three specific macrosystem influences (political suppression, institutional racism, and cultural oppression). When YCE scholars begin to make greater meaning of the foundations and critical work developed by Black youth civic activists, a more comprehensive field emerges. With the acknowledgment and inclusion of civic contributions created and implemented during historical eras, more profound meaning is gained of civic engagement among communities and people who have generally been disenfranchised. Coming to terms with their civic legacies developed from racial injustices provides a more comprehensive depiction of civic engagement as a field and body of literature.
Prediction of future wrinkles for middle‐aged women: A 7‐year longitudinal study on the progression of wrinkles in Japanese women
Authors: Nakamura Rie , Uehara Shizuka , Suematsu Ken , Ishitsuka Yukiko , Noma Hisashi
Published: March 2021

Background

It is commonly believed that there is serious heterogeneity in the rate of wrinkle progression among individuals. Although several skin characteristics have been shown to influence wrinkle progression, the ability to predict which individuals with skin characteristics are likely to develop wrinkles is still limited.

Objectives

The purpose of this study is to develop and validate an effective prediction model for longitudinal changes in wrinkles.

Methods

We collected annual wrinkle scores and multiple skin physiological characteristics in 48 Japanese women over a period of 7 years. We developed a multivariable prediction model for predicting future wrinkle status based on the various skin physiological characteristics using a linear mixed‐effects model.

Results

After variable selection by backwards, the final wrinkle prediction model included age, sebum volume, redness of skin color, lightness of skin color, and an interaction term between sebum volume and redness of skin color. The developed prediction model showed favorable prediction accuracy (R2 = 87.92%, 95% confidence interval 84.27%‐90.68%).

Conclusions

The developed model accurately predicted levels of wrinkles in Japanese women aged 22‐60 years. The prediction model is based on age and three practical skin characteristics, which might implicate an essential insight to prevent wrinkle progression in individuals.
A β‐lactamase gene of Fusarium oxysporum alters the rhizosphere microbiota of soybean
Authors: Chang Hao‐Xun , Noel Zachary A. , Chilvers Martin I.
Published: March 2021

The rhizosphere is a multitrophic environment, and for soilborne pathogens such as Fusarium oxysporum, microbial competition in the rhizosphere is inevitable before reaching and infecting roots. This study established a tritrophic interaction among the plant growth‐promoting rhizobacterium Burkholderia ambifaria, F. oxysporum and Glycine max (soybean) to study the effects of F. oxysporum genes on shaping the soybean microbiota. Although B. ambifaria inhibited mycelial growth and increased bacterial propagation in the presence of F. oxysporum, F. oxysporum still managed to infect soybean in the presence of B. ambifaria. RNA‐Seq identified a putative F. oxysporum secretory β‐lactamase‐coding gene, FOXG_18438 (abbreviated as Fo18438), that is upregulated during soybean infection in the presence of B. ambifaria. The ∆Fo18438 mutants displayed reduced mycelial growth towards B. ambifaria, and the complementation of full Fo18438 and the Fo18438 β‐lactamase domain restored mycelial growth. Using the F. oxysporum wild type, ∆Fo18438 mutants and complemented strains with full Fo18438, Fo18438 β‐lactamase domain or Fo18438 RTA1‐like domain for soil inoculation, 16S rRNA amplicon sequencing revealed that the abundance of a Burkholderia operational taxonomic unit (OTU) was increased in the rhizosphere microbiota infested by the strains with Fo18438 β‐lactamase domain. Non‐metric multidimensional scaling and PICRUSt2 functional analysis revealed differential abundance for the bacterial β‐lactam‐related functions when contrasting the genotypes of F. oxysporum. These results indicated that the Fo18438 β‐lactamase domain provides F. oxysporum with the advantage of growing into the soybean rhizosphere, where β‐lactam antibiosis is involved in microbial competition. Accordingly, this study highlights the capability of an F. oxysporum gene for altering the soybean rhizosphere and taproot microbiota.
A LysR Family Transcriptional Regulator Modulates Burkholderia cenocepacia Biofilm Formation and Protease Production
Authors: Wang Kai , Li Xia , Yang Chunxi , Song Shihao , Cui Chaoyu , Zhou Xiaofan , Deng Yinyue
Published: March 2021

Burkholderia cenocepaciais an important opportunistic pathogen in humans that utilizes the BDSF and AHL quorum-sensing (QS) systems to regulate biological functions and virulence. We demonstrated here that a new downstream regulator, Bcal3178 of the QS signaling network, controls biofilm formation and protease production.
Complete Genome Sequence of Shigella sonnei Strain SE6-1, Capable of Selenate Reduction
Authors: Nogrado Kathyleen , Cho Ahyeon , Han Dukki , Ho Cuong Tu , Fredrickson James K. , Lee Ji-Hoon
Published: March 2021

We report the complete genome sequence of selenate [Se(VI)]-reducing
Shigella sonnei
SE6-1, which was isolated from stream sediment from an industrial complex in Jeonju, South Korea. The genome sequence is 4,762,774 bp long, with a G+C content of 50.7% and 4,548 genes, including 4,440 coding sequences, 22 rRNA genes, and 86 tRNA genes.
Additional Feeding Reveals Differences in Immune Recognition and Growth of
Plasmodium
Parasites in the Mosquito Host
Authors: Kwon Hyeogsun , Simões Maria L. , Reynolds Rebekah A. , Dimopoulos George , Smith Ryan C.
Published: March 2021

Mosquitoes must blood feed multiple times to acquire and transmit malaria. However, the impact of an additional mosquito blood meal following malaria parasite infection has not been closely examined.
Supplemental Material: Annually resolved sediments in the classic Clarkia lacustrine deposits (Idaho, USA) during the middle Miocene Climate Optimum
Authors: Höfig Daianne , Zhang Yi Ge , al. et
Published: March 2021

Detailed methodology, supplemental figures, and separate data files containing raw U-Pb zircon data, μ-XRF elemental ratios, and color intensity variation.
Supplemental Material: Eruption risks from covert silicic magma bodies
Authors: Rooyakkers Shane , al. et
Published: March 2021

Details of methods, an outline of the geology of Krafla, supplemental details of the drilling encounters with magma, supplemental figures, and a spreadsheet containing all compositional data collected from Víti pumice samples.
Supplemental Material: New statistical quantification of the impact of active deformation on the distribution of submarine channels
Authors: Pizzi Marco , Whittaker A.C. , al. et
Published: March 2021

Additional details of the study area, methods, seismic imaging of the channels, and statistical analysis.