bluuebunny/crossref_metadata_2025 huggingface dataset:
The photomorphogenic repressors BBX28 and BBX29 integrate light and brassinosteroid signaling to inhibit seedling development in Arabidopsis
Authors: Cao Jing , Liang Yuxia , Yan Tingting , Wang Xuncheng , Zhou Hua , Chen Chen , Zhang Yingli , Zhang Beihong , Zhang Shuhao , Liao Juncheng , Cheng Shujing , Chu Jinfang , Huang Xi , Xu Dongqing , Li Jia , Deng Xing Wang , Lin Fang
Published: March 2022

B-box containing proteins (BBXs) integrate light and various hormonal signals to regulate plant growth and development. Here, we demonstrate that the photomorphogenic repressors BBX28 and BBX29 positively regulate brassinosteroid (BR) signaling in Arabidopsis thaliana seedlings. Treatment with the BR brassinolide stabilized BBX28 and BBX29, which partially depended on BR INSENSITIVE1 (BRI1) and BIN2. bbx28 bbx29 seedlings exhibited larger cotyledon aperture than the wild-type when treated with brassinazole in the dark, which partially suppressed the closed cotyledons of brassinazole resistant 1-1D (bzr1-1D). Consistently, overexpressing BBX28 and BBX29 partially rescued the short hypocotyls of bri1-5 and bin2-1 in both the dark and light, while the loss-of-function of BBX28 and BBX29 partially suppressed the long hypocotyls of bzr1-1D in the light. BBX28 and BBX29 physically interacted with BR-ENHANCED EXPRESSION1 (BEE1), BEE2, and BEE3 and enhanced their binding to and activation of their target genes. Moreover, BBX28 and BBX29 as well as BEE1, BEE2, and BEE3 increased BZR1 accumulation to promote the BR signaling pathway. Therefore, both BBX28 and BBX29 interact with BEE1, BEE2, and BEE3 to orchestrate light and BR signaling by facilitating the transcriptional activity of BEE target genes. Our study provides insights into the pivotal roles of BBX28 and BBX29 as signal integrators in ensuring normal seedling development.
EAR APICAL DEGENERATION1 regulates maize ear development by maintaining malate supply for apical inflorescence
Authors: Pei Yuanrong , Deng Yanan , Zhang Huairen , Zhang Zhaogui , Liu Jie , Chen Zhibin , Cai Darun , Li Kai , Du Yimo , Zang Jie , Xin Peiyong , Chu Jinfang , Chen Yuhang , Zhao Li , Liu Juan , Chen Huabang
Published: March 2022

Ear length (EL) is a key trait that contributes greatly to grain yield in maize (Zea mays). While numerous quantitative trait loci for EL have been identified, few causal genes have been studied in detail. Here we report the characterization of ear apical degeneration1 (ead1) exhibiting strikingly shorter ears and the map-based cloning of the casual gene EAD1. EAD1 is preferentially expressed in the xylem of immature ears and encodes an aluminum-activated malate transporter localizing to the plasma membrane. We show that EAD1 is a malate efflux transporter and loss of EAD1 leads to lower malate contents in the apical part of developing inflorescences. Exogenous injections of malate rescued the shortened ears of ead1. These results demonstrate that EAD1 plays essential roles in regulating maize ear development by delivering malate through xylem vessels to the apical part of the immature ear. Overexpression of EAD1 led to greater EL and kernel number per row and the EAD1 genotype showed a positive association with EL in two different genetic segregating populations. Our work elucidates the critical role of EAD1 in malate-mediated female inflorescence development and provides a promising genetic resource for enhancing maize grain yield.
Sucrose nonfermenting-1-related protein kinase 1 regulates sheath-to-panicle transport of nonstructural carbohydrates during rice grain filling
Authors: Hu Yuxiang , Liu Jiajun , Lin Yan , Xu Xuemei , Xia Yongqing , Bai Jiaqi , Yu Yongchao , Xiao Feng , Ding Yanfeng , Ding Chengqiang , Chen Lin
Published: March 2022

The remobilization of nonstructural carbohydrates (NSCs) reserved in rice (Oryza sativa) sheaths is essential for grain filling. This assimilate distribution between plant tissues and organs is determined by sucrose non-fermenting-1-related protein kinase 1 (SnRK1). However, the SnRK1-mediated mechanism regulating the sheath-to-panicle transport of NSCs in rice remains unknown. In this study, leaf cutting treatment was used to accelerate NSC transport in the rice sheaths. Accelerated NSC transport was accompanied by increased levels of OsSnRK1a mRNA expression, SnRK1a protein expression, catalytic subunit phosphorylation of SnRK1, and SnRK1 activity, indicating that SnRK1 activity plays an important role in sheath NSC transport. We also discovered that trehalose-6-phosphate, a signal of sucrose availability, slightly reduced SnRK1 activity in vitro. Since SnRK1 activity is mostly regulated by OsSnRK1a transcription in response to low sucrose content, we constructed an snrk1a mutant to verify the function of SnRK1 in NSC transport. NSCs accumulated in the sheaths of snrk1a mutant plants and resulted in a low seed setting rate and grain weight, verifying that SnRK1 activity is essential for NSC remobilization. Using phosphoproteomics and parallel reaction monitoring, we identified 20 SnRK1-dependent phosphosites that are involved in NSC transport. In addition, the SnRK1-mediated phosphorylation of the phosphosites directly affected starch degradation, sucrose metabolism, phloem transport, sugar transport across the tonoplast, and glycolysis in rice sheaths to promote NSC transport. Therefore, our findings reveal the importance, function, and possible regulatory mechanism of SnRK1 in the sheath-to-panicle transport of NSCs in rice.
Experts and climate change politicisation. A case study of the Environmental Protection Agency (1983–2015)
Authors: Loy Loredana
Published: March 2022

How did governmental experts respond publicly to the politicisation of climate change in the policy domain? Did they remain neutral to this process, resisted these efforts, or enabled them? Using longitudinal data derived from a content analysis of congressional testimonies provided by the Environmental Protection Agency (EPA) between 1983 and 2015, I find that the proportion of climate-related advocacy statements increased over time, yet their prevalence varied with the political context. As the agency’s position-taking on the issue intensified over time, this intensity was conditional on the political context. Most importantly, the EPA experts never denied the scientific basis of climate change, not even under presidential administrations that did, and instead advocated for climate action. These findings complicate traditional conceptualisations of experts as either independent from or subservient to politics, suggesting a more complex relationship where experts attempt to respond to contentious politics while maintaining continuity in their mission.
Pathologising ‘Refusal’: Prison, Health and Conscientious Objectors during the First World War
Authors: Hodgson Max
Published: March 2022

This article examines the extent to which the refusals of British conscientious objectors (COs) to fight during the First World War were pathologised through the lens of physical and mental health, and the ways in which such a pathology impacted their treatment in penal establishments. It argues that the government compromised the physical as well as the mental health of absolutist COs. The article also analyses the effects of the state’s pathologising efforts upon objectors, and the methods through which the physical bodies of COs were utilised against, or annexed by, the authorities. Drawing on Cabinet Minutes, Prison Commissioner Reports, and COs’ personal letters and memoir materials, it suggests that the case of COs offers an interesting comparison with the complex ways in which the phenomenon of ‘shell-shock’ was beginning to be understood in both somatic and psychological terms.
Rational deuteration of dronedarone attenuates its toxicity in human hepatic HepG2 cells
Authors: Tang Lloyd Wei Tat , Lim Royden Yu Ren , Venkatesan Gopalakrishnan , Chan Eric Chun Yong
Published: March 2022

Deuteration is a chemical modification strategy that has recently gained traction in drug development. The replacement of one or more hydrogen atom(s) in a drug molecule with its heavier stable isotope deuterium can enhance its metabolic stability and pharmacokinetic properties. However, it remains uninterrogated if rational deuteration at bioactivation “hot-spots” could attenuate its associated toxicological consequences. Here, our preliminary screening with benzofuran antiarrhythmic agents first revealed that dronedarone and its major metabolite N-desbutyldronedarone elicited a greater loss of viability and cytotoxicity in human hepatoma G2 (HepG2) cells as compared with amiodarone and its corresponding metabolite N-desethylamiodarone. A comparison of dronedarone and its in-house synthesized deuterated analogue (termed poyendarone) demonstrated that deuteration could attenuate its in vitro toxicity in HepG2 cells by modulating the extent of mitochondrial dysfunction, reducing the dissipation of mitochondrial membrane potential, and evoking a distinct apoptotic kinetic signature. Furthermore, although pretreatment with the CYP3A inducer rifampicin or the substitution of glucose with galactose in the growth media significantly augmented the loss of cell viability elicited by dronedarone and poyendarone, a lower loss of cell viability was consistently observed in poyendarone across all concentrations. Taken together, our preliminary investigations suggested that the rational deuteration of dronedarone at its benzofuran ring reduces aberrant cytochrome P450 3A4/5-mediated bioactivation, which attenuated its mitochondrial toxicity in human hepatic HepG2 cells.
Genome-wide circular RNA profiling and competing endogenous RNA regulatory network analysis provide new insights into the molecular mechanisms underlying early somatic embryogenesis in Dimocarpus longan Lour.
Authors: Chen Xiaohui , Xu Xiaoping , Zhang Shuting , Munir Nigarish , Zhu Chen , Zhang Zihao , Chen Yukun , Xuhan Xu , Lin Yuling , Lai Zhongxiong
Published: March 2022

Circular RNAs (circRNAs) are widely involved in plant growth and development. However, the function of circRNAs in plant somatic embryogenesis (SE) remains elusive. Here, by using high-throughput sequencing, a total of 5029 circRNAs were identified in the three stages of longan (Dimocarpus longan Lour.) early SE. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that differentially expressed (DE) circRNA host genes were enriched in the ‘non-homologous end-joining’ (NHEJ) and ‘butanoate metabolism’ pathways. In addition, the reactive oxygen species (ROS) content during longan early SE was determined. The results indicated that ROS-induced DNA double-strand breaks may not depend on the NHEJ repair pathway. Correlation analyses of the levels of related metabolites (glutamate, γ-aminobutyrate and pyruvate) and the expression levels of circRNAs and their host genes involved in butanoate metabolism were performed. The results suggested that circRNAs may act as regulators of the expression of cognate mRNAs, thereby affecting the accumulation of related compounds. A competing endogenous RNA (ceRNA) network of DE circRNAs, DE mRNAs, DE long noncoding RNAs (lncRNAs) and DE microRNAs (miRNAs) was constructed. The results showed that the putative targets of the noncoding RNA (ncRNAs) were significantly enriched in the KEGG pathways ‘mitogen-activated protein kinase signaling’ and ‘nitrogen metabolism’. Furthermore, the expression patterns of the candidate circRNAs, lncRNAs, miRNAs and mRNAs confirmed the negative correlation between miRNAs and ceRNAs. In addition, two circRNA overexpression vectors were constructed to further verify the ceRNA network correlations in longan early SE. Our study revealed the potential role of circRNAs in longan early SE, providing new insights into the intricate regulatory mechanism underlying plant SE.
Peer Support Specialists: An Underutilized Resource in the Criminal Justice System for Opioid Use Disorder Management?
Authors: Hamilton Jonah , Ti Lianping , Korchinski Mo , Nolan Seonaid
Published: March 2022

In the wake of North America's worsening overdose crisis, the overrepresentation of individuals incarcerated with an opioid use disorder (OUD) constitutes a population at an incredibly high risk for adverse health outcomes, including death. In response, a number of important initiatives such as the provision of opioid agonist therapy to individuals with opioid addiction while incarcerated have been implemented. Although improving access to evidence-based treatment for OUD is an obvious urgent need, equally important is the need to implement novel interventions to help reduce morbidity and mortality among this high-risk group. Peer support specialists (ie, individuals with lived or shared experience) have previously been demonstrated to effectively help clients navigate the healthcare system, reintegrate within their community, and successfully adhere to their individual treatment and recovery goals. Given the known association between individuals with an OUD and exposure to the criminal justice system, routine inclusion of peer support specialists as part of the addiction interdisciplinary care team in these settings may be an effective opportunity to improve health outcomes and prevent death among incarcerated individuals with an OUD.
Effects of Exercise Interventions on Aerobic Capacity in Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction: Systematic Review and Network Meta-Analysis
Authors: Gomes-Neto Mansueto , Rodrigues Durães André , Roever Leonador , Magalhães Silva Cassio , Gonzalez Nogueira Alves Iura , Bernardone Saquetto Micheli , Ellingsen Øyvind , Oliveira Carvalho Vitor
Published: March 2022

Exercise is an important component of rehabilitation care for patients with heart failure with preserved ejection fraction (HFpEF). However, it is unclear which type of physical rehabilitation exercise is most effective. Thus, the aim of this study was to determine the relative effects of different types of exercise interventions on aerobic capacity measured by peak oxygen consumption (VO2 peak; in mL/kg·min) in patients with HFpEF. We searched different electronic databases until December 2020 for randomized controlled trials that evaluated the effects of different types of exercise interventions on VO2 peak of patients with HFpEF. Mean difference, standardized mean difference (SMD), and 95% confidence intervals (CIs) were calculated. Fixed and random-effects Bayesian network meta-analysis was used to compare the relative effectiveness of the different exercise interventions. Nineteen studies met the study criteria, including 720 patients. Comparing the physical rehabilitation interventions with usual care (control group), inspiratory muscle training was the highest ranked exercise intervention with an SMD of 3.6 mL/kg·min (95% CI, 2.3–4.8), followed by the group undergoing high-intensity interval training with a significant pooled improvement in VO2 peak 3.5 (95% CI, 2.6–4.4) and combined aerobic and resistance exercise with an SMD of 3.2 (95% CI, 1.4–5.0). The inspiratory muscle training, high-intensity interval training, and combined aerobic and resistance exercise were the highest ranked physical rehabilitation intervention to improve VO2 peak. These interventions should be considered as a component in the care of patients with HFpEF. Registration: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021256442.
The T Category of Distal Extrahepatic Bile Duct Carcinoma
Authors: Jun Sun-Young , Shin Jae Hoon , Chun Jihyun , Kang Hyo Jeong , Hong Seung-Mo
Published: March 2022

The T category of distal extrahepatic bile duct carcinoma (DBDC) is based on invasion depth from the basal lamina to the deepest infiltrating tumor cells. Recently, invasive tumor thickness (ITT) was proposed, defined as maximal vertical distance of invasive tumor components regardless of the basal lamina. We compared the predictive value of T category, and ITT grading in 424 surgically resected DBDCs. DBDCs were categorized as 6 Tis (1.4%), 134 T1 (<5 mm; 31.6%), 204 T2 (5 to 12 mm; 48.1%), and 80 T3 (>12 mm; 18.9%). With ITT, there were 6 G0 (no invasion; 1.4%), 3 G1 (<1 mm; 0.7%), 90 G2 (≥1 and <5 mm; 21.2%), 188 G3 (≥5 and <10 mm; 44.4%), and 137 G4 (≥10 mm; 32.3%). The 5-year survival rates of T1, T2, and T3 were 58.9%, 44.2%, and 18.2%, and those of ITT G1, G2, G3, and G4 were 33.3%, 54.1%, 51.6%, and 26.7%, respectively. The T category discriminated patient survival by overall (P<0.001) and pairwise (T1 vs. T2, P=0.007; T2 vs. T3, P<0.001) comparisons. ITT grading distinguished survival by overall and between G3-G4 (both P<0.001), with no survival differences observed between G1-G2 and G2-G3 comparisons. The T category more accurately discriminated patient survival than ITT grading. To determine the T category for DBDCs, (1) longitudinal sectioning on gross examination, especially for DBDCs with large papillary or nodular growth patterns; (2) evaluation of serial sections or alternative hematoxylin and eosin slides; (3) use of a straight or curved baseline depending on the shape of the peritumoral normal bile duct wall and/or the basal lamina of the peritumoral normal biliary epithelia/biliary intraepithelial neoplasias are recommended.
Cranioplasty With Customized Craniofacial Implants and Intraoperative Resizing for Single-Stage Reconstruction Following Oncologic Resection of Skull Neoplasms
Authors: Ben-Shalom Netanel , Asemota Anthony O. , Belzberg Micah , Harnof Sagi , Huang Judy , Lim Michael , Brem Henry , Gordon Chad
Published: March 2022

Background:

Craniectomies requiring skull reconstruction are indicated following oncological resection of masses involving the underlying brain and/or skull. Immediate cranioplasties have previously been performed using suboptimal hand-bending or molding techniques using “off – the – shelf” products. Today with computer – aided design, customized craniofacial implants have become widely available for personalized reconstruction of resected bone and soft tissue. We present here the largest series to date of single stage reconstruction using alloplastic biomaterials in consecutive patient series with oversized customized implants.

Methods:

A single-surgeon, retrospective, 8-year study was conducted on all consecutive patients undergoing single stage cranioplasty with prefabricated implants using a myriad of biomaterials. All outcomes were analyzed in detail and compared with previous studies utilizing similar alloplastic implants.

Results:

In total, 56 patients underwent resection of skull neoplasms and subsequent cranioplasty reconstruction using customized implants. The most common neoplasms were meningiomas (39%). The most common complications seen among patients were dehiscence – (7%), and extrusion of implant – (3.5%). There was no significant difference in the incidence of postoperative complications between patients who had postoperative chemotherapy/radiotherapy versus those that did not (22.2% versus 13.1%, P = 0.39). One-year follow-up revealed acceptable cranial contour and symmetry in all 56 cases.

Conclusions:

This is a consecutive case series of prefabricated single-stage cranioplasty, following resection of brain tumors with bone extension or skull bone neoplasm, demonstrating excellent results with regards to safety and patient satisfaction. There are several advantages such as comprehensive resection and reconstruction plan using 3D models, shorter operative time, and better restoration of complex anatomy.
Preoperative Arterial Coil Embolization for Temporomandibular Joint (TMJ) Surgery in Children with TMJ Ankylosis
Authors: Worede Fikadu , Alsaikhan Naif , Chang Corissa P. , Granquist Eric J. , Cahill Anne Marie
Published: March 2022

Temporomandibular joint (TMJ) ankylosis in children can alter facial development and affect oral hygiene and function. Surgical release of the ankylosis is the mainstay of treatment. The authors hypothesize that preoperative arterial coil embolization is safe and effective in preventing major blood loss during TMJ surgery (loss prompting blood transfusion or hemodynamic instability requiring vasoactive medication administration) in children with TMJ ankylosis. Patients < 16 years who were diagnosed with TMJ ankylosis (<15 maximal interincisal opening) and had embolization before surgery in the last 5 years were included. Out of 9 initial search results, 3 patients were excluded (age > 16). Information gathered were patient demographics, diagnostic imaging, procedural details, complications, and clinical outcomes. Six patients, mean age 11.14 years (range 7–15 years) year and a mean weight of 40.8 ± 19 kg were included. Underlying etiologies for TMJ ankylosis: Pierre Robin Syndrome (n = 2), juvenile rheumatoid arthritis (n = 1), Goldenhar's syndrome (n = 1), trauma (n = 1), and micrognathia (n = 1). Neck computed tomography angiogram before embolization demonstrated an intimate approximation between the internal maxillary artery (IMAX) and/or external carotid artery and ankylotic mass in all patients. Eight successful embolizations were performed without procedural complication. In 1 patient with angiographic evidence of surgical internal maxillary artery ligation, embolization was performed via collaterals. Surgery was performed within 48 hours of embolization. Airway access during surgery was via nasal intubation (n = 4), oral intubation (n = 3). The estimated blood loss (EBL) during surgery was 78.33 ± 47.08 ml. Three patients had subsequent TMJ surgery with a mean estimated blood loss of 73.33 ± 46.18 ml. After a mean follow-up of 17 ± 15 months, patients showed a 13.8mm mean increment of maximal interincisal opening with 95% CI (5.74−21.9), P < 0.007.
Healthy Lifestyle Behaviors and Viewpoints Among Members of an Alzheimer Prevention Registry
Authors: Reynolds Gretchen O. , Tremont Geoffrey , Santorelli Gennarina D. , Denby Charles , Margolis Seth A. , Ott Brian R.
Published: March 2022

Background:

Research on Alzheimer disease and related dementias is increasingly focused on preventative strategies to target modifiable risk factors (eg, exercise, diet, cognitive stimulation) to reduce risk of cognitive decline, though it remains difficult for adults to adopt and maintain these behaviors on their own.

Methods/Participants:

In this survey study, we examined knowledge about modifiable risk factors for dementia, engagement in healthy lifestyle behaviors, and associated barriers/facilitators in an Alzheimer disease prevention registry of at-risk, cognitively normal adults (n=135: 77% female; 96% Caucasian and non-Hispanic; mean age=66.1; 79% with family history of dementia; 46% with subjective memory decline).

Results:

Participants reported high levels of engagement in exercise (mean 3.4 d/wk), a healthy diet (60% with a healthy/balanced diet), and cognitive stimulation (52% engaging in cognitive stimulation 3 to 7 d/wk), and most (56% to 57%) reported moderate to high knowledge about dementia and modifiable risk factors. Family history of dementia was associated with greater knowledge of risk factors for dementia (P=0.017), but not with knowledge of lifestyle recommendations to reduce risk (P=0.85). Most participants (63%) reported a preference for walking/running over other types of aerobic exercise. On average, participants reported that they would be willing to increase healthy lifestyle behaviors to achieve “moderate” risk reduction for dementia (∼21% to 23%, on a scale from 0% to 40%, reflecting mildly to substantially reduced risk).

Conclusion:

Results broaden our understanding of current habits and willingness to engage in healthy lifestyle behaviors, which may inform individualized lifestyle interventions and/or design of prevention trials, particularly among at-risk adults with subjective or mild cognitive concerns, who may be especially motivated and able to engage in lifestyle interventions, to optimize brain health and reduce risk of cognitive decline.
STOmicsDB: a database of Spatial Transcriptomic data
Authors: Xu Zhicheng , Wang Weiwen , Yang Tao , Chen Jing , Huang Yan , Gould Joshua , Du Wensi , Yang Fan , Li Ling , Lai Tingting , Hua Cong , Hu Shoujie , Cai Jia , Li Honge , You Lijin , Zeng Wenjun , Wang Bo , Liu Longqi , Xu Xun , Chen Fengzhen , Wei Xiaofeng
Published: March 2022

Recent technological development in spatial transcriptomics allows researchers to measure gene expression of cells and their spatial locations at the almost single-cell level, which generates detailed biological insight into biological processes. However, specialized spatial transcriptomics databases are rare. Here, we present the Spatial TranscriptOmics DataBase (STOmicsDB), a user-friendly database with multifunctions including search of relevant publications and tools, public dataset visualization, customized specialized databases, new data archive, and online analysis. The current version of STOmicsDB consists of 141 curated spatial transcript datasets covering 12 species, and includes 5,618 spatial multi-omics publications and 674 tools. STOmicsDB is freely accessible at https://db.cngb.org/stomics/.
Astrocyte mitochondria produce nitric oxide from nitrite to modulate cerebral blood flow during brain hypoxia
Authors: Christie Isabel N , Theparambil Shefeeq M , Doronin Maxim , Hosford Patrick S , Brazhe Alexey , Hobbs Adrian , Semyanov Alexey , Abramov Andrey Y , Angelova Plamena , Gourine Alexander V
Published: March 2022

In low oxygen conditions, increases in cerebral blood flow maintain brain oxygen delivery but the mechanisms underlying hypoxia-induced dilations of cerebral vasculature are incompletely understood. Here we show that astrocytes accumulate nitrite and in response to hypoxia produce nitric oxide via mitochondrial reduction of nitrite by a molybdenum-containing enzyme sulfite oxidase. These data suggest that astrocytes can modulate cerebral blood flow in accord with brain tissue oxygenation via mitochondrial production of nitric oxide.
Dynamic and selective engrams emerge with memory consolidation
Authors: Tomé Douglas Feitosa , Zhang Ying , Aida Tomomi , Sadeh Sadra , Roy Dheeraj S. , Clopath Claudia
Published: March 2022

Episodic memories are encoded by sparse populations of neurons activated during an experience.1 These neural ensembles constitute memory engrams that are both necessary and sufficient for inducing recall even long after memory acquisition.2 This suggests that following encoding, engrams are stabilized to reliably support memory retrieval. However, little is known about the temporal evolution of engrams over the course of memory consolidation or how it impacts mnemonic properties. Here we employed computational and experimental approaches to examine how the composition and selectivity of engrams change with memory consolidation. We modeled engram cells using a spiking recurrent neural network that yielded three testable predictions: memories transition from unselective to selective as neurons are removed from and added to the engram, inhibitory activity during recall is essential for memory selectivity, and inhibitory synaptic plasticity during memory consolidation is critical for engrams to become selective. Using the Cal-Light system to tag activated neurons in vivo with high spatiotemporal precision3 as well as optogenetic and chemogenetic techniques, we conducted contextual fear conditioning experiments that supported each of our model’s predictions. Our results reveal that engrams are dynamic even within hours of memory consolidation and that changes in engram composition mediated by inhibitory synaptic plasticity are crucial for the emergence of memory selectivity. These findings challenge classical theories of stable memory traces and point to a close link between engram state and memory expression.
Peritoneal M2 macrophage-derived extracellular vesicles as natural multi-target nanotherapeutics to attenuate cytokine storm after severe infections
Authors: Wang Yizhuo , Liu Shuyun , Li Lan , Li Ling , Zhou Xueli , Wan Meihua , Lou Peng , Zhao Meng , Lv Ke , Yuan Yujia , Chen Younan , Lu Yanrong , Cheng Jingqiu , Liu Jingping
Published: March 2022

Cytokine storm is a primary cause for multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophages-derived extracellular vesicles (M2-EVs) are multi-target nanotherapeutics to resolve cytokine storm. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines. Systemically administrated M2-EVs entered major organs and were taken up by phagocytes (e.g., macrophages). M2-EVs treatment effectively reduced excessive cytokine (e.g., TNF-α and IL-6) releasein vitroandin vivo, thereby attenuated oxidative stress and multiple organ (lung, liver, spleen and kidney) damage in endotoxin-induced cytokine storm. Moreover, M2-EVs simultaneously inhibited multiple key proinflammatory pathways (e.g., NF-κB, JAK-STAT and p38 MAPK) by regulating complex miRNA-gene and gene-gene networks, and this effect was collectively mediated by many functional cargos (miRNAs and proteins) in EVs. In addition to the direct anti-inflammatory role, human peritoneal M2-EVs expressed angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2 spike protein, and thus could serve as nanodecoys to prevent SARS-CoV-2 pseudovirus infectionin vitro. As cell-derived nanomaterials, the therapeutic index of M2-EVs can be further improved by genetic/chemical modification or loading with specific drugs. This study highlights that peritoneal M2-EVs are promising multifunctional nanotherapeutics to attenuate infectious diseases-related cytokine storm.
Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis
Authors: Zhang Weidao , Tang Min , Wang Lin , Zhou Hu , Gao Jing , Chen Zhongliang , Zhao Bo , Zheng Ping
Published: March 2022

Replication stress is a major source of endogenous DNA damage. Despite that numerous proteins have been identified on replication forks to modulate fork or replication machinery activities, it remains unexplored whether non-coding RNAs can localize on stalled forks and play critical regulatory roles. Here we identify an uncharacterized lncRNA NONMMUT028956 (Lnc956 for short) predominantly expressed in mouse embryonic stem cells. Lnc956 is recruited to stalled replication forks to prevent fork collapse and preserve genomic stability, and is essential for mouse embryogenesis. Mechanistically, it drives assembly of the Lnc956-TRIM28-HSP90B1 ribonucleoprotein (RNP) complex on stalled forks in an inter-dependent manner downstream of ATR signaling. This RNP complex physically associates with MCM2-7 hexamer via TRIM28 and directly regulates the CMG helicase retention on chromatin. The regulation of RNP on CMG retention is mediated by HSP90B1’s chaperoning function. These findings reveal a novel pathway which actively regulates replisome retention to prevent fork collapse.
Independent effect and joint effect of polygenic liabilities for schizophrenia and bipolar disorder on cognitive aging and education attainment
Authors: Wu Chi-Shin , Hsu Chia-Lin , Lin Mei-Chen , Su Mei-Hsin , Lin Yen-Feng , Chen Chia-Yen , Hsiao Po-Chang , Pan Yi-Jiun , Chen Pei-Chun , Huang Yen-Tsung , Wang Shi-Heng
Published: March 2022

To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD) to better understand their nosology, this study explored the independent and joint effects of polygenic liabilities for SCZ and BPD on cognitive aging and educational attainment among a collection of 80318 unrelated community participants from the Taiwan Biobank. Using the Psychiatric Genomics Consortium meta-analysis as a discovery sample, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific, differentiated from BPD, PRS (PRSSCZvsBPD). Based on the sign concordance of the susceptibility variants with SCZ and BPD, PRSSCZ was split into PRSSCZ_concordant and PRSSCZ_discordant and PRSBPD was split into PRSBPD_concordant and PRSBPD_discordant. Linear regression models were used to estimate the association with cognitive aging as measured by the Mini-Mental State Examination (MMSE) in individuals aged ≥ 60 years. Ordinal logistic regression models were used to estimate the association with educational attainment. PRSSCZ was negatively associated with MMSE (beta=-0.063, p<0.001), while PRSBPD was positively associated with MMSE (beta=0.04, p=0.01). A larger difference between PRSSCZ and PRSBPD was associated with lower MMSE scores (beta=-0.052, p<0.001). Both PRSSCZ_concordant and PRSSCZ_discordant were negatively associated with MMSE scores, without a synergistic effect. There was a complex interaction between PRSBPD_concordant and PRSBPD_discordant on the MMSE scores. PRSSCZ+BPD (beta=-0.09, p=0.01) and PRSSCZvsBPD (beta=-0.13, p<0.001) predicted a decrease in MMSE scores during the follow-up. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvs BPD was negatively associated with educational attainment. This study provides evidence for the contrasting effect of polygenic liabilities for SCZ and BPD on cognitive aging and partially supports the hypothesis that the heterogeneity of SCZ and the positive association of polygenic liability for SCZ with education might be attributed to the shared part with BPD.
Obesity, hypertension and tobacco use associated with left ventricular remodelling and hypertrophy in South African Women: Birth to Twenty Plus Cohort
Authors: Kolkenbeck-Ruh Andrea , Soepnel Larske M. , Crouch Simone H. , Naidoo Sanushka , Smith Wayne , Norris Shane A. , Davies Justine , Ware Lisa J.
Published: March 2022

Background

Left ventricular hypertrophy (LVH) is a known marker of increased risk in developing future life-threating CVD, though it is unclear how health risk factors, such as obesity, blood pressure and tobacco use, associate with left ventricular (LV) remodelling and LVH across generations of urban African populations.

Methods

Black female adults (n=123; age: 29-68 years) and their children (n=64; age: 4-10; 55% female) were recruited from the Birth to Twenty Plus Cohort in Soweto, South Africa. Tobacco and alcohol use, physical activity, presence of diabetes mellitus, heart disease and medication were self-reported. Height, weight, and blood pressure were measured in triplicate. Echocardiography was used to assess LV mass at end-diastole, perpendicular to the long axis of the LV and indexed to body surface area to determine LVH.

Results

Hypertension and obesity prevalence were 35.8% and 59.3% for adults and 45.3% and 6.3% for children. Self-reported tobacco use in adults was 22.8%. LVH prevalence was 35.8% (n=44) in adults (75% eccentric; 25% concentric), and 6.3% (n=4) in children (all eccentric). Prevalence of concentric remodelling was 15.4% (n=19) in adults and observed in one child. In adults, obesity (OR: 2.54 (1.07-6.02; p=0.02) and hypertension (3.39 (1.08-10.62; p=0.04) significantly increased the odds of LVH, specifically eccentric LVH, while concentric LVH was associated with self-reported tobacco use (OR: 4.58 (1.18-17.73; p=0.03; n=11). Although no logistic regression was run within children, of the four children LVH, three had elevated blood pressure and the child with normal blood pressure was overweight.

Conclusions

The association between obesity, hypertension, tobacco use and LVH in adults, and the 6% prevalence of LVH in children, calls for stronger public health efforts to control risk factors and monitor children at who are risk.
Single-exposure X-ray phase imaging microscopy with a grating interferometer
Authors: Wolf Andreas , Akstaller Bernhard , Cipiccia Silvia , Flenner Silja , Hagemann Johannes , Ludwig Veronika , Meyer Pascal , Schropp Andreas , Schuster Max , Seifert Maria , Weule Mareike , Michel Thilo , Anton Gisela , Funk Stefan
Published: March 2022

The advent of hard X-ray free-electron lasers enables nanoscopic X-ray imaging with sub-picosecond temporal resolution. X-ray grating interferometry offers a phase-sensitive full-field imaging technique where the phase retrieval can be carried out from a single exposure alone. Thus, the method is attractive for imaging applications at X-ray free-electron lasers where intrinsic pulse-to-pulse fluctuations pose a major challenge. In this work, the single-exposure phase imaging capabilities of grating interferometry are characterized by an implementation at the I13-1 beamline of Diamond Light Source (Oxfordshire, UK). For comparison purposes, propagation-based phase contrast imaging was also performed at the same instrument. The characterization is carried out in terms of the quantitativeness and the contrast-to-noise ratio of the phase reconstructions as well as via the achievable spatial resolution. By using a statistical image reconstruction scheme, previous limitations of grating interferometry regarding the spatial resolution can be mitigated as well as the experimental applicability of the technique.
In situphase formation during high-temperature synthesis in clad mechanocomposites based on the Ti–Al system
Authors: Loginova Marina , Sobachkin Alexey , Sitnikov Alexander , Yakovlev Vladimir , Myasnikov Andrey , Sharafutdinov Marat , Tolochko Boris , Golovina Tatiana
Published: March 2022

Anin situsynchrotron experimental study of phase formation dynamics in clad mechanocomposites of Ti–Al systems during high-temperature synthesis was performed. Cladding of the obtained mechanocomposites was carried out with an SiO2target, with a deposition time of 40 min. The high-temperature synthesis was performed using the thermal explosion method based on a microwave induction heater in thein situmode on an experimental setup adapted to synchrotron radiation time-resolved diffractometry. The influence of the cladding on the macrokinetic parameters of synthesisin situwas investigated experimentally. It was found that for an ignition temperatureTig= 650 ± 10°C, the maximum synthesis temperatures were in the rangeTmax= 1380–1465°C. The characteristic heating speed was 525 K min−1. The sequence and temperature–time interval of phase formation are determined. The formation of the TiAl, TiAl3and Ti3Al compounds begins atT= 661°C. AtTmax= 1465.6°C, the synthesis product is multiphase, the structures of the formed TiAl3(content about 70%) and TiAl (content about 25%) have a nonequilibrium state. At the stage of system annealing withT= 1384.9°C, the reaction of the components occurs with the formation of almost monophase TiAl (content of more than 90%); Ti occupies the rest.
Compressibility of structural modulation waves in the chain compounds BaCoX
2O7 (X = As, P): a powder study
Authors: Das Ranjana R. , Leclercq Bastien , Bouvier Pierre , Arévalo-López Angel M. , Goujon Céline , Itié Jean-Paul , Polian Alain , Mentré Olivier , Colin Claire V.
Published: March 2022

BaCoX
2O7 (X = As, P) are built on magnetic 1D units in which strong aperiodic undulations originate from incommensurate structural modulations with large atomic displacive amplitudes perpendicular to the chain directions, resulting in very unique multiferroic properties. High-pressure structural and vibrational properties of both compounds have been investigated by synchrotron X-ray powder diffraction and Raman spectroscopy at room temperature and combined with density functional calculations. A structural phase transition is observed at 1.8 GPa and 6.8 GPa in BaCoAs2O7 and BaCoP2O7, respectively. Sharp jumps are observed in their unit-cell volumes and in Raman mode frequencies, thus confirming the first-order nature of their phase transition. These transitions involve the disappearance of the modulation from the ambient-pressure polymorph with clear spectroscopic fingerprints, such as reduction of the number of Raman modes and change of shape on some peaks. The relation between the evolution of the Raman modes along with the structure are presented and supported by density functional theory structural relaxations.
Plasma monopole antenna array
Authors: Papadimopoulos Athanasios , Di Iorio Alessio
Published: March 2022

Purpose

This study aims to investigate different configurations of plasma antenna arrays and multiple combinations based on whether the plasma dischargers are set ON or OFF, to assess the coupling, interference and overall performance of these plasma antenna arrays.

Design/methodology/approach

In this paper, the authors investigate the operation and performance of the combined use of sets of antennas and plasma antenna elements in plasma monopole antenna arrays.

Findings

The authors find that there can be significant modifications of the plasma antenna arrays’ gain and pattern in multiple ways, merely by switching different combinations of plasma columns ON and OFF.

Originality/value

High-density plasma antenna arrays have been examined in this paper and it has been shown that they are capable of reaching high antenna gain. Moreover, the overall antenna array’s gain and pattern can be considerably transformed in multiple ways by turning ON and OFF different combinations of plasma antenna elements. Finally, the electromagnetic coupling and interference coming from these plasma antennas can be greatly reduced.
A viable MBA for BoP students: PiMS in rural Kasaragod, Kerala
Authors: John Kishore Thomas , Kamala Raghavan Ajith Kumar
Published: March 2022

Learning outcomes

Participants will learn to analyze the basis of consumer segmentation in management education. It will specifically highlight the importance of positioning in influencing the marketing strategy of a firm and discuss the importance of a differentiated-low cost strategy to gain competitive advantage. The case will familiarize students with the business environment of rural India, and the applicability of the 4A’s and the 5D’s framework. Finally, the case will help participants understand the difference between a rural market and a Bottom-of-Pyramid (BoP) market.

Case overview/synopsis

A rural MBA institute for BoP students is grappling with the problem of low admissions, leading to an existential crisis. Two divergent options are presented to the protagonist. The first is to close down the B-school and use the infrastructure and facilities for a well-funded government skill development program which is vocational and intended for creating blue-collar workers. The second is to find ways to bolster the B-school to ensure that it gets adequate student enrollment, thereby leading to profitability.

Complexity academic level

This case is suitable for an undergraduate or MBA course in marketing management, rural marketing in India, South-Asian marketing or strategic marketing.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or e-mail support@emeraldinsight.com to request teaching notes. There is an accompanying spreadsheet with the case for studying the market. It contains relevant market data that would support analysis of the case. Comments are added for easy understanding. Instructors can access the separate spreadsheet that works out the break-even calculations for the fee structure of the institute. Instructions on calculations as well as comments are added for easy understanding.

Subject code

CSS 8: Marketing.
A deeper understanding of student preferences for in-class video use: a segmentation analyses of needs, group differences and preference clusters
Authors: Salehudin Imam , Alpert Frank
Published: March 2022

Purpose

This study analyzed segment differences of student preference for video use in lecture classes and university use of video lecture classes. The authors then conducted novel gap analyses to identify gaps between student segments' preferences for videos versus their level of exposure to in-class videos. Multivariate analysis of variance (MANOVA) was used to identify significant factors that explain the gaps.

Design/methodology/approach

Segment differences of student preference for video use in lecture classes and university use of video lecture classes were analyzed. Novel gap analyses were then conducted to identify gaps between student segments' preferences for videos versus their level of exposure to in-class videos. MANOVA was used to identify significant factors that explain the gaps.

Findings

Gap analysis of video preference relative to video exposure showed a bimodal distribution, with an approximately even split between students with an overall deficit (44.5%) and surplus (47%) of in-class videos. Deficit means students preferred to see more videos than what the lecturer showed them. Surplus means the lecturer showed students more videos than they preferred to see. Further analyses break down the deficits and surpluses based on the type of videos shown.

Practical implications

Results are useful as an effective diagnostic tool for education managers because they are not at the individual student level but rather by course level. One implication for educational managers is that a one-size-fits-all approach for all courses will benefit some students and annoy others.

Originality/value

This paper extends Alpert and Hodkinson’s (2019) findings by identifying preference clusters and performing segmentation analyses based on finer-grained disaggregated data analysis.
Enhancing the quality of project management through action research
Authors: Coghlan David , Shani Abraham B. (Rami) , Coughlan Paul
Published: March 2022

Purpose

The article brings the quality characteristics of action research to project management and explores how these quality characteristics of well-designed and executed action research can inform and enhance the practice of project management.

Design/methodology/approach

A reflective paper.

Findings

The article identifies five imperatives in bringing together action research and project management. The authors argue that project management may be conducted in a manner that is rigorous, reflective and relevant.

Research limitations/implications

The integration of project management and action research is not empirically described. Therefore, researchers are encouraged to test and further develop the model in relation to the design and management of projects.

Practical implications

Practical questions are posed for implementation.

Social implications

The integration of action research and project management is a collaborative venture and the engagement imperative emphasizes that collaboration.

Originality/value

By bringing together action research and project management the article integrates five imperatives: design, engagement, improvement, action and research and quality characteristics of action research to enhance project management as rigorous, reflective and relevant.