bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of 3D volume growth rate for drug activity evaluation in meningioma clinical trials: the example of the CEVOREM study
Authors: Graillon Thomas , Ferrer Loic , Siffre Jason , Sanson Marc , Peyre Matthieu , Peyrière Hadrien , Mougel Grégory , Autran Didier , Tabouret Emeline , Figarella-Branger Dominique , Barlier Anne , Kalamarides Michel , Dufour Henry , Colin Thierry , Chinot Olivier
Published: February 2021

Background

We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome.

Methods

We performed a post hoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR undertreatment.

Results

Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR = 6.13%/month; mean undertreatment 3DVGR = −18.7%/month within 3 first months and −0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume undertreatment (65.5%) (mean pretreatment 3DVGR = 6.09%/month; undertreatment 3DVGR = −0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR = 46.9%/month; mean undertreatment 3DVGR = 19.2%/month within the first 3 months). Patients with class 3 lesions had a significantly worse progression-free survival (PFS) rate than class 1 and 2 ones.

Conclusions

Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or nonactivity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.
Sport-Related Structural Brain Injury and Return to Play: Systematic Review and Expert Insight
Authors: Zuckerman Scott L , Yengo-Kahn Aaron M , Tang Alan R , Bailes Julian E , Beauchamp Kathryn , Berger Mitchel S , Bonfield Christopher M , Camarata Paul J , Cantu Robert C , Davis Gavin A , Ellenbogen Richard G , Ellis Michael J , Feuer Hank , Guazzo Eric , Harris Odette A , Heppner Peter , Honeybul Stephen , Manley Geoff , Maroon Joseph C , Miele Vincent J , Nahed Brian V , Okonkwo David O , Oppenlander Mark E , Petty Jerry , Sabin H Ian , Samadani Uzma , Sherburn Eric W , Sheridan Mark , Tator Charles H , Theodore Nicholas , Timmons Shelly D , Woodworth Graeme F , Solomon Gary S , Sills Allen K
Published: February 2021

BACKGROUND

Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI.

OBJECTIVE

To provide key insight for operative management and RTP following SRSBI using a (1) focused systematic review and (2) survey of expert opinions.

METHODS

A systematic literature review of SRSBI from 2012 to present in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a cross-sectional survey of RTP in SRSBI by 31 international neurosurgeons was conducted.

RESULTS

Of 27 included articles out of 241 systematically reviewed, 9 (33.0%) case reports provided RTP information for 12 athletes. To assess expert opinion, 31 of 32 neurosurgeons (96.9%) provided survey responses. For acute, asymptomatic SRSBI, 12 (38.7%) would not operate. Of the 19 (61.3%) who would operate, midline shift (63.2%) and hemorrhage size > 10 mm (52.6%) were the most common indications. Following SRSBI with resolved hemorrhage, with or without burr holes, the majority of experts (>75%) allowed RTP to high-contact/collision sports at 6 to 12 mo. Approximately 80% of experts did not endorse RTP to high-contact/collision sports for athletes with persistent hemorrhage. Following craniotomy for SRSBI, 40% to 50% of experts considered RTP at 6 to 12 mo. Linear regression revealed that experts allowed earlier RTP at higher levels of play (β = –0.58, 95% CI –0.111, –0.005, P = .033).

CONCLUSION

RTP decisions following structural brain injury in athletes are markedly heterogeneous. While individualized RTP decisions are critical, aggregated expert opinions from 31 international sports neurosurgeons provide key insight. Level of play was found to be an important consideration in RTP determinations.
Percutaneous Trigeminal Nerve Stimulation Induces Cerebral Vasodilation in a Dose-Dependent Manner
Authors: Li Chunyan , White Timothy G , Shah Kevin A , Chaung Wayne , Powell Keren , Wang Ping , Woo Henry H , Narayan Raj K
Published: February 2021

BACKGROUND

The trigeminal nerve directly innervates key vascular structures both centrally and peripherally. Centrally, it is known to innervate the brainstem and cavernous sinus, whereas peripherally the trigemino-cerebrovascular network innervates the majority of the cerebral vasculature. Upon stimulation, it permits direct modulation of cerebral blood flow (CBF), making the trigeminal nerve a promising target for the management of cerebral vasospasm. However, trigeminally mediated cerebral vasodilation has not been applied to the treatment of vasospasm.

OBJECTIVE

To determine the effect of percutaneous electrical stimulation of the infraorbital branch of the trigeminal nerve (pTNS) on the cerebral vasculature.

METHODS

In order to determine the stimulus-response function of pTNS on cerebral vasodilation, CBF, arterial blood pressure, cerebrovascular resistance, intracranial pressure, cerebral perfusion pressure, cerebrospinal fluid calcitonin gene-related peptide (CGRP) concentrations, and the diameter of cerebral vessels were measured in healthy and subarachnoid hemorrhage (SAH) rats.

RESULTS

The present study demonstrates, for the first time, that pTNS increases brain CGRP concentrations in a dose-dependent manner, thereby producing controllable cerebral vasodilation. This vasodilatory response appears to be independent of the pressor response induced by pTNS, as it is maintained even after transection of the spinal cord at the C5-C6 level and shown to be confined to the infraorbital nerve by administration of lidocaine or destroying it. Furthermore, such pTNS-induced vasodilatory response of cerebral vessels is retained after SAH-induced vasospasm.

CONCLUSION

Our study demonstrates that pTNS is a promising vasodilator and increases CBF, cerebral perfusion, and CGRP concentration both in normal and vasoconstrictive conditions.
Soybean Yellow Stripe-like 7 is a symbiosome membrane peptide transporter important for nitrogen fixation
Authors: Gavrin Aleksandr , Loughlin Patrick C , Brear Ella , Griffith Oliver W , Bedon Frank , Suter Grotemeyer Marianne , Escudero Viviana , Reguera Maria , Qu Yihan , Mohd-Noor Siti N , Chen Chi , Osorio Marina Borges , Rentsch Doris , González-Guerrero Manuel , Day David A , Smith Penelope Mary Collina
Published: February 2021

Legumes form a symbiosis with rhizobia that convert atmospheric nitrogen (N2) to ammonia and provide it to the plant in return for a carbon and nutrient supply. Nodules, developed as part of the symbiosis, harbor rhizobia that are enclosed in a plant-derived symbiosome membrane (SM) to form an organelle-like structure called the symbiosome. In mature nodules exchanges between the symbionts occur across the SM. Here we characterize Yellow Stripe-like 7 (GmYSL7), a Yellow stripe-like family member localized on the SM in soybean (Glycine max) nodules. It is expressed specifically in infected cells with expression peaking soon after nitrogenase becomes active. Unlike most YSL family members, GmYSL7 does not transport metals complexed with phytosiderophores. Rather, it transports oligopeptides of between four and 12 amino acids. Silencing GmYSL7 reduces nitrogenase activity and blocks infected cell development so that symbiosomes contain only a single bacteroid. This indicates the substrate of YSL7 is required for proper nodule development, either by promoting symbiosome development directly or by preventing inhibition of development by the plant. RNAseq of nodules where GmYSL7 was silenced suggests that the plant initiates a defense response against rhizobia with genes encoding proteins involved in amino acid export downregulated and some transcripts associated with metal homeostasis altered. These changes may result from the decrease in nitrogen fixation upon GmYSL7 silencing and suggest that the peptide(s) transported by GmYSL7 monitor the functional state of the bacteroids and regulate nodule metabolism and transport processes accordingly. Further work to identify the physiological substrate for GmYSL7 will allow clarification of this role.
Genome-wide analysis in response to nitrogen and carbon identifies regulators for root AtNRT2 transporters
Authors: Ruffel Sandrine , Chaput Valentin , Przybyla-Toscano Jonathan , Fayos Ian , Ibarra Catalina , Moyano Tomas , Fizames Cécile , Tillard Pascal , O’Brien Jose Antonio , Gutiérrez Rodrigo A , Gojon Alain , Lejay Laurence
Published: February 2021

In Arabidopsis (Arabidopsis thaliana), the High-Affinity Transport System (HATS) for root nitrate (NO3−) uptake depends mainly on four NRT2 NO3− transporters, namely NRT2.1, NRT2.2, NRT2.4, and NRT2.5. The HATS is the target of many regulations to coordinate nitrogen (N) acquisition with the N status of the plant and with carbon (C) assimilation through photosynthesis. At the molecular level, C and N signaling pathways control gene expression of the NRT2 transporters. Although several regulators of these transporters have been identified in response to either N or C signals, the response of NRT2 gene expression to the interaction of these signals has never been specifically investigated, and the underlying molecular mechanisms remain largely unknown. To address this question we used an original systems biology approach to model a regulatory gene network targeting NRT2.1, NRT2.2, NRT2.4, and NRT2.5 in response to N/C signals. Our systems analysis of the data identified three transcription factors, TGA3, MYC1, and bHLH093. Functional analysis of mutants combined with yeast one-hybrid experiments confirmed that all three transcription factors are regulators of NRT2.4 or NRT2.5 in response to N or C signals. These results reveal a role for TGA3, MYC1, and bHLH093 in controlling the expression of root NRT2 transporter genes.
Transcription-associated metabolomic adjustments in maize occur during combined drought and cold stress
Authors: Guo Qianqian , Li Xia , Niu Li , Jameson Paula E , Zhou Wenbin
Published: February 2021

Although simultaneous drought and cold stress occurs, especially in northwestern and eastern regions of China, and is an important factor limiting agricultural productivity, there are few studies focusing on plant responses to a combination of drought and cold stress. Here, by partially overlapping drought and cold stresses, we characterized the acclimation of maize (Zea mays B73) to these two stresses using physiological measurements, as well as comparative transcriptomics combined with metabolomics and hormonal analyses during the stress treatments and recovery stages. The combined drought and cold stress and drought stress alone were accompanied by a decline in photosynthetic capacity and enhanced transcriptional response, and subsequent recovery of these following removal from stress, whereas cold stress alone was accompanied by irreversible damage to photosynthetic capacity and chloroplast structure. The stress combination induced transcription-associated metabolomic alterations, in which raffinose, trehalose-6-phosphate, and proline accumulated, and monosaccharide abundance increased. Concomitantly, the increased abscisic acid (ABA) content and upregulated ABA signaling pathway may have provided the transcriptional regulation for the metabolic changes. In a parallel experiment, ABA treatments prior to exposure of the plants to cold stress primed the plants to survive the cold stress, thus confirming a key role for the endogenous ABA activated by the drought pretreatment in acclimation of the plants to cold. We present a model showing that the plant response to the combined stress is multi-faceted and reveal an ABA-dependent maize acclimation mechanism to the stress combination.
Non-SUSY heterotic string vacua of Gepner models with vanishing cosmological constant
Authors: Aoyama Koji , Sugawara Yuji
Published: February 2021

We study a natural generalization of the results given in K. Aoyama and Y. Sugawara, Prog. Theor. Exp. Phys. 2020, 103B01 (2020) to heterotic strings. Namely, starting from the generic Gepner models for Calabi –Yau three-folds, we construct non-SUSY heterotic string vacua with vanishing cosmological constant at the one-loop level. We especially focus on asymmetric orbifolding based on some discrete subgroup of the chiral $U(1)$ action which acts on both the Gepner model and the $SO(32)$ or $E_8\times E_8$ sector. We present a classification of the relevant orbifold models leading to the string vacua with the properties mentioned above. In some cases, the desired vacua can be constructed in a manner quite similar to those given in the previous paper for the type II string, in which the orbifold groups contain two generators with discrete torsions. On the other hand, we also have simpler models that are just realized as asymmetric orbifolds of cyclic groups with only one generator.
A Theory of Collateral for the Lender of Last Resort*
Authors: Choi Dong Beom , Santos João A C , Yorulmazer Tanju
Published: February 2021

We consider a macroprudential approach to analyze the optimal lending policy for the central bank, focusing on spillover effects that policy exerts on money markets. Lending against high-quality collateral protects central banks against losses, but can adversely affect liquidity creation in markets since high-quality collateral gets locked up with the central bank rather than circulating in markets. Lending against low-quality collateral creates counterparty risk but can improve liquidity in markets. We illustrate the optimal policy incorporating these trade-offs. Contrary to what is generally accepted, lending against high-quality collateral can have negative effects, whereas it may be optimal to lend against low-quality collateral.
Surface energy and separation mechanics of droplet interface phospholipid bilayers
Authors: Huang Y. , Chandran Suja V. , Tajuelo J. , Fuller G. G.
Published: February 2021

Droplet interface bilayers are a convenient model system to study the physio-chemical properties of phospholipid bilayers, the major component of the cell membrane. The mechanical response of these bilayers to various external mechanical stimuli is an active area of research because of its implications for cellular viability and the development of artificial cells. In this article, we characterize the separation mechanics of droplet interface bilayers under step strain using a combination of experiments and numerical modelling. Initially, we show that the bilayer surface energy can be obtained using principles of energy conservation. Subsequently, we subject the system to a step strain by separating the drops in a step-wise manner, and track the evolution of the bilayer contact angle and radius. The relaxation time of the bilayer contact angle and radius along with the decay magnitude of the bilayer radius were observed to increase with each separation step. By analysing the forces acting on the bilayer and the rate of separation, we show that the bilayer separates primarily through the peeling process with the dominant resistance to separation coming from viscous dissipation associated with corner flows. Finally, we explain the intrinsic features of the observed bilayer separation by means of a mathematical model comprising the Young–Laplace equation and an evolution equation. We believe that the reported experimental and numerical results extend the scientific understanding of lipid bilayer mechanics, and that the developed experimental and numerical tools offer a convenient platform to study the mechanics of other types of bilayers.
Comparative genome analysis of three Group A Streptococcus dysgalactiae subsp. equisimilis strains isolated in Japan
Authors: Ishihara Haruka , Ogura Kohei , Nguyen Van An , Miyohi-Akiyama Tohru , Okamoto Shigefumi , Takemoto Norihiko
Published: February 2021

Introduction

. Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a β-hemolytic streptococcus that causes severe invasive streptococcal infections, especially in the elderly and people with underlying diseases. SDSE strains are primarily characterized by Lancefield group G or C antigens.

Hypothesis/Gap Statement. We have previously reported the prevalence of Lancefield group A SDSE (GA-SDSE) strains in Japan and have analysed the draft genome sequences of these strains. As GA-SDSE is a rare type of SDSE, only one complete genome has been sequenced to date.

Aim. The present study is focused on genetic characteristics of GA-SDSE strains. In order to examine molecular characteristics, we also tested growth inhibition of other streptococci by GA-SDSE.

Methodology. We determined the complete genome sequences of three GA-SDSE strains by two new generation sequencing systems (short-read and long-read sequencing data). Using the sequences, we also conducted a comparative analysis of GA-SDSE and group C/G SDSE strains. In addition, we tested multiplex and quantitative PCRs targeting the GA-SDSE, group G SDSE, and

S. pyogenes

.

Results. We found a group-specific conserved region in GA-SDSE strains that is composed of genes encoding predicted anti-bacteriocin and streptococcal lantibiotic (Sal) proteins. Multiplex and quantitative PCRs targeting the GA-SDSE-specific region were able to distinguish between GA-SDSE, other SDSE, and

S. pyogenes

strains. The growth of GA-SDSE was suppressed in the presence of group G SDSE, indicating a possible explanation for the low frequency of isolation of GA-SDSE.

Conclusion. The comparative genome analysis shows that the genome of GA-SDSE has a distinct arrangement, enabling the differentiation between

S. pyogenes

, GA-SDSE, and other SDSE strains using our PCR methods.
Targeting fronto-limbic dysfunctions via intermittent theta burst stimulation as a novel treatment for Functional Movement Disorders
Authors: Spagnolo Primavera A , Parker Jacob , Horovitz Silvina , Hallett Mark
Published: February 2021

Background

Neuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD), although there is no direct causal evidence of this relationship. Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, in this proof-of-concept study, we investigated safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD.

Methods

Six subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day, for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. FMD symptom severity was assessed at baseline, during treatment and 24 hours after receiving the last iTBS session.

Results

Multiples doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and also influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a significant decrease in negative valence and an increase in positive valence levels following iTBS. Furthermore, we also observed a marked reduction in FMD symptom severity post stimulation.

Conclusions

Corticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research.
Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines
Authors: Huang Baoying , Dai Lianpan , Wang Hui , Hu Zhongyu , Yang Xiaoming , Tan Wenjie , Gao George F.
Published: February 2021

Recently, the emerged and rapidly spreading SARS-CoV-2 variant of concern (VOC) 501Y.V2 with 10 amino acids in spike protein were found to escape host immunity induced by infection or vaccination. Global concerns have been raised for its potential to affect vaccine efficacy. Here, we evaluated the neutralization activities of two vaccines developed in China against 501Y.V2. One is licensed inactivated vaccine BBIBP-CorV and the other one is recombinant dimeric receptor-binding domain (RBD) vaccine ZF2001. Encouragingly, both vaccines largely preserved neutralizing titres, with slightly reduction, against 501Y.V2 authentic virus compare to their titres against both original SARS-CoV-2 and the currently circulating D614G virus. These data indicated that 501Y.V2 variant will not escape the immunity induced by vaccines targeting whole virus or RBD.
Basal-to-classical phenotypic switch of pancreatic cancer cells upon integration into the duodenal epithelium
Authors: Bozóky Benedek , Fernández Moro Carlos , Strell Carina , Ernberg Ingemar , Szekely Laszlo , Gerling Marco , Bozóky Béla
Published: February 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes can be defined that differ in prognosis. Single-cell sequencing has recently revealed that these subtypes coexist in individual tumors. However, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall. Using multiplex immunohistochemistry, we show that PDAC cells revert to non-destructive growth and undergo differentiation towards the classical subtype upon integration into the duodenal epithelium. Our results tightly link microenvironmental cues to the PDAC molecular subtype and open the door to a systematic investigation of microenvironmental control in human pancreatic cancer.
Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats
Authors: Fouyssac Maxime , Peña-Oliver Yolanda , Puaud Mickaёl , Lim Nicole , Giuliano Chiara , Everitt Barry J , Belin David
Published: February 2021

The inflexible pursuit of drug-seeking and great tendency to relapse that characterize addiction has been associated with the recruitment of the dorsolateral striatum-dependent habit system. However, the mechanisms by which maladaptive drug-seeking habits influence subsequent relapse are obscure. Here, we show that rats with a long history of cocaine-seeking, controlled by drug-paired cues and mediated by the habit system, show highly exacerbated drug-seeking at relapse that is not mediated by cocaine withdrawal. This heightened tendency to relapse is underpinned by transient engagement of the dorsomedial striatum goal-directed system and reflects emergent negative urgency resulting from the prevention of enacting the seeking habit during abstinence. These results reveal a novel mechanism underlying the pressure to relapse and indicate a target for preventing it.

One Sentence Summary

Instrumental deprivation triggers flexibility in the well-established cue-controlled cocaine-seeking behaviour.
Distinct neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex
Authors: Hill Paul F. , Seger Sarah E. , Yoo Hye Bin , King Danielle R. , Lega Bradley C. , Rugg Michael D.
Published: February 2021

Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood-oxygen-level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modelling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70-150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30-70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex.

Significance Statement

The blood-oxygen-level-dependent (BOLD) signal forms the basis of fMRI but provides only an indirect measure of neural activity. Task-related modulation of BOLD signals are typically equated with changes in gamma-band activity; however, relevant empirical evidence comes largely from the neocortex. We examined neurophysiological correlates of the BOLD signal in the hippocampus, where the differing neural architecture might result in a different relationship between the respective signals. We identified a positive relationship between encoding-related changes in BOLD and gamma-band activity in frontal, temporal, and parietal cortex. This effect was reversed in the hippocampus, where BOLD and gamma-band effects negatively covaried. These results suggest regional variability in the transfer function between neural activity and the BOLD signal in the hippocampus and neocortex.
Spray-induced gene silencing for disease control is dependent on the efficiency of pathogen RNA uptake
Authors: Qiao Lulu , Lan Chi , Capriotti Luca , Ah-Fong Audrey , Sanchez Jonatan Nino , Hamby Rachael , Heller Jens , Zhao Hongwei , Glass N. Louise , Judelson Howard S. , Mezzetti Bruno , Niu Dongdong , Jin Hailing
Published: February 2021

Recent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the development ofSpray-InducedGeneSilencing (SIGS) for plant disease management. In this study, we aimed to determine the efficacy of SIGS across a variety of eukaryotic microbes. We first examined the efficiency of RNA uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen. We observed efficient double-stranded RNA (dsRNA) uptake in the fungal plant pathogensBotrytis cinerea,Sclerotinia sclerotiorum,Rhizoctonia solani,Aspergillus niger, andVerticillium dahliae, but no uptake inColletotrichum gloeosporioides, and weak uptake in a beneficial fungus,Trichoderma virens. For the oomycete plant pathogen,Phytophthora infestans, RNA uptake was limited, and varied across different cell types and developmental stages. Topical application of dsRNA targeting virulence-related genes in the pathogens with high RNA uptake efficiency significantly inhibited plant disease symptoms, whereas the application of dsRNA in pathogens with low RNA uptake efficiency did not suppress infection. Our results have revealed that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types. The success of SIGS for plant disease management can largely be determined by the pathogen RNA uptake efficiency.
Investigating the validity of the Strengths and Difficulties Questionnaire to assess ADHD in young adulthood
Authors: Riglin Lucy , Agha Sharifah Shameem , Eyre Olga , Jones Rhys Bevan , Wootton Robyn E , Thapar Ajay K , Collishaw Stephan , Stergiakouli Evie , Langley Kate , Thapar Anita
Published: February 2021

Attention Deficit Hyperactivity Disorder (ADHD) symptoms typically onset early in development and persist into adulthood for many. Robust investigation of symptom continuity and discontinuity requires repeated assessments using the same measure, but research is lacking into whether measures used to assess ADHD symptoms in childhood are also valid in adulthood. The Strengths and Difficulties Questionnaire (SDQ) has been widely used to measure ADHD symptoms in children, but little is known about its utility to measure ADHD in adulthood. We used Receiver Operating Characteristic (ROC) curve analyses to examine the validity of the SDQ hyperactivity/ADHD subscale to distinguish between cases and non-cases of DSM-5 ADHD classified using the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) at age 25 years in a UK population cohort (N=4121). Analyses suggested that the SDQ ADHD subscale had high accuracy in distinguishing ADHD cases from non-cases in young adulthood (area under the curve=0.90, 95% CI=0.87-0.93) and indicated a lower cut-point for identifying those who may have an ADHD diagnosis in this age group compared to that currently recommended for younger ages.Our findings suggest that the SDQ is suitable for ADHD research across different developmental periods, which will aid the robust investigation of ADHD from childhood to young adulthood.

Highlights

The SDQ is widely used to measure ADHD symptoms in children

We investigated the validity of the SDQ to assess ADHD at age 25 years

The SDQ ADHD subscale had high accuracy in distinguishing DSM-5 ADHD cases from non-cases

A lower cut-point is needed to identify ADHD diagnosis in young adulthood compared to younger ages

The SDQ is appropriate for ADHD research across different development periods
Adult vaccination in Brazil: a cross-sectional survey on physicians’ prescription habits
Authors: Serra Fernando B , Ribeiro Diogo , Batista Paula M , Moreira Thais N F
Published: February 2021

OBJECTIVE

To characterize adult and older adult vaccination practices of physicians from various medical specialties in Brazil, identify the barriers influencing prescription of vaccines to these populations, and evaluate the physicians’ knowledge on routinely prescribed vaccines.

METHODS

Cross-sectional survey conducted in Brazil between June-August 2018. Eligible physicians included those from general practice/family medicine, geriatrics, cardiology, gynecology, endocrinology, infectious disease and pulmonology. The survey’s questions addressed the physicians’ prescription habits, sociodemographic and clinical practice characteristics, barriers to vaccines’ prescription to adult and older adult patients, and physicians’ knowledge regarding routinely prescribed vaccines. The study focused on the vaccines recommended by the Brazilian Society of Immunization (SBIm) for adults and older adults. Study sample was stratified according to the number of physicians per specialty and Brazilian region.

RESULTS

A total of 1068 surveys were completed. The vaccines prescribed by the highest proportions of physicians were Influenza (>90% of physicians for adults and older adults), Hepatitis B (adults: 87%; older adults: 59%) and Yellow Fever (adults: 77.7%; older adults: 58.5%). Underprescription was reported by less than 20% of prescribing physicians for all adult and older adult recommended vaccines. The most common barriers to vaccination were the high vaccine cost, lack of time during appointments and lack of patient interest. Knowledge on target populations, dosage schedule and availability in the Unified Public Health System (SUS) was generally low.

CONCLUSIONS

The results showed a considerable variability of prescribing habits across recommended vaccines and medical specialties. Although most prescribing physicians seem to be aware of the importance of adult and older adults vaccination, knowledge deficits on vaccines’ target populations, dosage schedule and availability in the SUS may hamper their ability to prescribe vaccines to all patients with an indication.
Microglia drive pockets of neuroinflammation in middle age
Authors: Moca Eric N. , Lecca Daniela , Hope Keenan T. , Tweedie David , Sidhu Shanaya , Masukawa Lindsay , Sitoy Hannah , Mathew Rose , Saban Daniel R. , Greig Nigel H. , De Biase Lindsay M.
Published: February 2021

During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to insults, positioning these cells to have profound impact on the functional integrity of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions and CNS insults in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored. Here, we analyze and manipulate microglial aging within the basal ganglia, brain circuits that exhibit prominent regional microglial heterogeneity and where neurons are vulnerable to functional decline and neurodegenerative disease. We demonstrate that microglia in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) exhibit unique and premature responses to aging, compared to microglia elsewhere. This is associated with ‘pockets’ of VTA/SNc neuroinflammation that are likely to compromise local synaptic function as early as middle age. Surprisingly, these early aging responses of VTA and SNc microglia do not appear to be driven by systemic inflammation, local neuron death, or early responses of astrocytes to aging. Finally, CX3CR1 receptor knockout can exacerbate and microglial ablation/repopulation can suppress early VTA microglial aging; these manipulations have been shown to affect brain-wide microglial aging, and our data demonstrate that their impact is not uniform throughout the CNS. Our findings reveal a previously unappreciated regional variation in the onset and magnitude of microglial aging responses and suggest that there may be important links between local microglial aging and vulnerability of nearby neurons to functional decline and disease.
Validation and classification of RNA binding proteins identified by mRNA interactome capture
Authors: Vaishali  , Dimitrova-Paternoga Lyudmila , Haubrich Kevin , Sun Mai , Ephrussi Anne , Hennig Janosch
Published: February 2021

RNA binding proteins (RBPs) take part in all steps of the RNA life cycle and are often essential for cell viability. Most RBPs have a modular organization and comprise a set of canonical RNA binding domains. However, in recent years a number of high-throughput mRNA interactome studies on yeast, mammalian cell lines and whole organisms have uncovered a multitude of novel mRNA interacting proteins that lack classical RNA binding domains. Whereas a few have been confirmed to be direct and functionally relevant RNA binders, biochemical and functional validation of RNA binding of most others is lacking. In this study, we employed a combination of NMR spectroscopy and biochemical studies to test the RNA binding properties of six putative RNA binding proteins. Half of the analysed proteins showed no interaction, whereas the other half displayed weak chemical shift perturbations upon titration with RNA. One of the candidates we found to interact weakly with RNA in vitro is Drosophila melanogaster End binding protein 1 (EB1), a master regulator of microtubule plus-end dynamics. Further analysis showed that EB1’s RNA binding occurs on the same surface as that with which EB1 interacts with microtubules. RNA immunoprecipitation and colocalization experiments suggest that EB1 is a rather non-specific, opportunistic RNA binder. Our data suggest that care should be taken when embarking on an RNA binding study involving these unconventional, novel RBPs, and we recommend initial and simple in vitro RNA binding experiments.
Dynamic histone acetylation in floral volatile synthesis and emission in petunia flowers
Authors: Patrick Ryan M. , Huang Xing-Qi , Dudareva Natalia , Li Ying
Published: February 2021

Biosynthesis of secondary metabolites relies on primary metabolic pathways to provide precursors, energy, and cofactors, thus requiring coordinated regulation of primary and secondary metabolic networks. However, to date it remains largely unknown how this coordination is achieved. Using Petunia hybrida flowers, which emit high levels of phenylpropanoid/benzenoid volatile organic compounds (VOCs), we uncovered genome-wide dynamic deposition of histone H3 lysine 9 acetylation (H3K9ac) during anthesis as an underlying mechanism to coordinate primary and secondary metabolic networks. The observed epigenome reprogramming is accompanied by transcriptional activation, at gene loci involved in primary metabolic pathways that provide precursor phenylalanine, as well as secondary metabolic pathways to produce volatile compounds. We also observed transcriptional repression among genes involved in alternative phenylpropanoid branches that compete for metabolic precursors. We show that GNAT family histone acetyltransferase(s) (HATs) are required for the expression of genes involved in VOC biosynthesis and emission, by using chemical inhibitors of HATs, and by knocking down a specific HAT, ELP3, through transient RNAi. Together, our study supports that chromatin level regulatory mechanisms may play an essential role in activating primary and secondary metabolic pathways to regulate VOC synthesis in petunia flowers.

HIGHLIGHT

Our study shows that posttranslational modification of histones is essential for regulating the biosynthesis and emission of floral scent compounds, thus providing insights into chromatin level regulation of secondary metabolism.
Single calcium channel nanodomains drive presynaptic calcium entry at lamprey reticulospinal presynaptic terminals
Authors: Ramachandran S , Rodgriguez S , Potcoava M , Alford S
Published: February 2021

Synchronous neurotransmission is central to efficient information transfer in neural circuits, requiring precise coupling between action potentials, Ca2+entry and neurotransmitter release. However, determinations of Ca2+requirements for release, which may originate from entry through single voltage-gated Ca2+channels, remain largely unexplored in simple active zone synapses common in the nervous system. Understanding these requirements is key to addressing Ca2+channel and synaptic dysfunction underlying numerous neurological and neuropsychiatric disorders. Here, we present single channel analysis of evoked active zone Ca2+entry, using cell-attached patch clamp and lattice light sheet microscopy over active zones at single central lamprey reticulospinal presynaptic terminals. Our findings show a small pool (mean of 23) of Ca2+channels at each terminal, comprising subtypes N-type (CaV2.2), P/Q-type (CaV2.1) and R-type (CaV2.3), available to gate neurotransmitter release. Significantly, of this pool only 1-6 (mean of 4) channels open upon depolarization. High temporal fidelity lattice light sheet imaging reveals AP-evoked Ca2+transients exhibiting quantal amplitude variations between action potentials and stochastic variation of precise locations of Ca2+entry within the active zone. Further, Ca2+channel numbers at each active zone correlate to the number of presynaptic primed synaptic vesicles. Together, our findings indicate 1:1 association of Ca2+channels with primed vesicles, suggesting Ca2+entry via as few as one channel may trigger neurotransmitter release.
Co-linear Chaining with Overlaps and Gap Costs
Authors: Jain Chirag , Gibney Daniel , Thankachan Sharma V.
Published: February 2021

Co-linear chaining has proven to be a powerful heuristic for finding near-optimal alignments of long DNA sequences (e.g., long reads or a genome assembly) to a reference. It is used as an intermediate step in several alignment tools that employ a seed-chain-extend strategy. Despite this popularity, efficient subquadratic-time algorithms for the general case where chains support anchor overlaps and gap costs are not currently known. We present algorithms to solve the co-linear chaining problem with anchor overlaps and gap costs inÕ(n) time, wherendenotes the count of anchors. We also establish the first theoretical connection between co-linear chaining cost and edit distance. Specifically, we prove that for a fixed set of anchors under a carefully designed chaining cost function, the optimal ‘anchored’ edit distance equals the optimal co-linear chaining cost. Finally, we demonstrate experimentally that optimal co-linear chaining cost under the proposed cost function can be computed orders of magnitude faster than edit distance, and achieves correlation coefficient above 0.9 with edit distance for closely as well as distantly related sequences.
Frequent coexistence of closely related tree species on a small scale in temperate evergreen forests in Japan
Authors: Watanabe Shuntaro , Maesako Yuri
Published: February 2021

Understanding how biotic interaction affects species composition and distribution is a major challenge in community ecology. In plants, negative reproductive interaction among closely related species (i.e., reproductive interference) is known to hamper the coexistence of congenic species. Since the magnitude of reproductive interference in plants depends on pollen flow distance, we hypothesized that the coexistence of congeners on a small spatial scale would be less likely to occur by chance but that such coexistence would be likely to occur on a scale larger than pollen flow distance. In the present study, we tested this hypothesis using spatially explicit woody plant survey data. Contrary to our prediction, congenic tree species often coexisted at the finest spatial scale and significant exclusive distribution was not detected. Our results suggest that cooccurrence of congenic tree species is not structured by reproductive interference, and they indicate the need for further research to explore the factors that mitigate the effects of reproductive interference.
Leveraging competitiveness to develop optimal strategies: evidence from the restaurant industry
Authors: Chiu Chia-Ning
Published: February 2021

Purpose

Performance evaluation is a good way to improve competitiveness, and leveraging competitiveness is vital to developing optimal strategies and sustainable development for the growing restaurant industry in the USA and across the globe. This study can benefit from the methods to inform business strategies and decisions. Through the combination of two methods, this paper aims to provide novel perspectives to realize each restaurant company’s resource allocation and performance, to know their market position compared to with other competitors, and then to develop their own business strategies.

Design/methodology/approach

This study proposes an application of slack-based measure (SBM) to determine input excesses and output shortfalls of the restaurant industry. Subsequently, context-dependent data envelopment analysis (DEA) is used to identify the level of each restaurant company and compute the relative attractiveness and progress scores for each restaurant at each level, positioning each restaurant company’s stance in their markets.

Findings

The empirical results reveal that management teams need to pay more attention to human resources, asset management and food cost control because the analysis of SBM model shows an opportunity for restaurant companies to adjust their hiring numbers to reach the optimal amount of employees. In addition, restaurant companies are categorized by their efficient frontiers into four levels using context-dependent DEA. Furthermore, the findings provide the four quadrants that each restaurant company falls into. Each of those four quadrants can guide the types of strategies a restaurant should adopt.

Originality/value

This study can help the publicly traded restaurant companies to identify their market position with target benchmarks, and then to develop optimal strategies and future plans for growth.
Measuring regional competitiveness on the basis of entrepreneurship, technological readiness and quality of institutions
Authors: Moirangthem Nirmalkumar Singh , Nag Barnali
Published: February 2021

Purpose

Developing composite index-regional entrepreneurship, technological readiness and institution quality index (RETRIQ) of regional entrepreneurship, technology readiness and quality of institution to measure regional competitiveness. This study, also, aims to test econometrically the effectiveness of the index in capturing the economic performance of the sub-national regions.

Design/methodology/approach

The data of eight indicators used in the index are from sources available freely in the public domain. The causal relationship analysis is done using panel data of 10 years from 2008 to 2017 for 32 Indian states/union territories. The generalized method of moments (GMM) is used for this dynamic regression estimation.

Findings

Based on RETRIQ, 32 states and union territories of India have ranked. The estimation using GMM shows a significant association between the composite index and economic growth.

Research limitations/implications

The limitations of the study include the broad assumption that these sub-national regions belong to a uniform macro-economic and technology environment and data constraints as it is a longitudinal study. Then, the implication of the study is that the composite index-RETRIQ could capture differences in regional competitiveness explaining regional economic disparity.

Practical implications

The index will be useful for policy implications in the assessment of competitiveness disparity.

Originality/value

It is a composite index of regional entrepreneurship, technological readiness and quality of the institution. The panel data across states along 10 years series is novel.
Assessment of e-service quality performance of university libraries
Authors: Trivedi Dharmendra , Bhatt Atul , Trivedi Mayank , Patel Pankajray Vinodchandra
Published: February 2021

Purpose

This empirical study aims to measure the performance of electronic service quality and related infrastructure in a state university library and suggests the strategies for further improvement based on this study.

Design/methodology/approach

The data collection was done through a survey questionnaire based on the 22 attributes of four e-Service quality dimensions rated on five-point Likert scale. The sample population consisted of 239 respondents comprising of different categories of users of university library.

Findings

The results of this study indicated that all four dimensions rated by the users fell between mean score 3 to 4 (good), the highest score was received in dimension online public access catalogue (OPAC) and internet service with followed by Library website, Library electronic equipment’s and e-User education. Out of total 22 e-Service quality attributes, none of the attributes received score above 4 (excellent), which indicates that still university library need to improve the current performance of e-Service quality and to take remedial steps to enhance the existing e-services and infrastructure.

Practical implications

Findings from this study could assist university library authority to sustain and enhance performance of e-Services that could achieve the core journey of the modern university libraries.

Originality/value

This study was the first endeavour for measurement of the performance of e-Service quality and related infrastructure of federal university libraries in India.