bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-vaccination neutralization responses to Omicron sub-variants
Authors: Jacobsen Henning , Katzmarzyk Maeva , Higdon Melissa M , Jiménez Viviana Cobos , Sitaras Ioannis , Bar-Zeev Naor , Knoll Maria Deloria
Published: September 2022

Background

The emergence of the Omicron variant (B.1.1.529) which correlated with dramatic losses in cross-neutralization capacity of post-vaccination sera raised concerns about the effectiveness of COVID-19 vaccines against infection and disease. Clinically relevant sub-variants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, and BA.4/5) subsequently emerged rapidly.

Methods

We evaluated published and pre-print studies reporting sub-variant specific reductions in cross-neutralization compared to the prototype strain of SARS-CoV-2 and between sub-variants. Median fold-reduction across studies was calculated by sub-variant and vaccine platform.

Results

Among 153 studies with post-vaccination data, after primary vaccination the sub-variant specific fold-reduction in neutralization capacity compared to the prototype antigen varied widely, from median 4.2-fold for BA.3 to 21.9-fold for BA.4/5; in boosted participants fold-reduction was similar for all sub-variants (5.9-fold to 7.1-fold) except for BA.4/5 which was 12.7-fold. Relative to BA.1, the other Omicron sub-variants had similar neutralization capacity post-primary vaccination (range median 0.8-fold to 1.1-fold) and post-booster (0.9-fold to 1.2-fold) except for BA.4/5 which was higher (2.0-fold). Omicron sub-variant specific responder rates were low post-primary vaccination (range median 33.5% to 56.7%) compared to the prototype (median 96.0%), but improved post-booster (range median 85.4% to 92.6%).

Conclusion

Fold-reductions in neutralization titers among Omicron sub-variants compared to the prototype strain varied widely post-primary vaccination but were comparable post-booster, except for BA.4/5 which had higher fold-reduction (2-fold relative to BA.1). Considering large fold-decreases in neutralization titers to the parental strain for all Omicron sub-variants, vaccine effectiveness is very likely to be reduced against all Omicron sub-variants, and probably more so against Omicron BA.4/5.
The impact of income-support interventions on life course risk factors and health outcomes during childhood: a systematic review in high income countries
Authors: Boccia Delia , Maritano Silvia , Pizzi Costanza , Richiardi Matteo G , Lioret Sandrine , Richiardi Lorenzo
Published: September 2022

In high income countries one in five children still lives in poverty. This is known to adversely shape the life course health trajectory of these children; however, much less is understood on whether social and fiscal policies have the capacity to reverse this damage, which intervention is likely to be most effective and when these interventions should be delivered to maximise their impact. This systematic review attempts to address these questions by looking at the impact of income-support interventions delivered during the first 1,000 days of life on cardiovascular, metabolic, respiratory and mental health outcomes. The review was restricted to experimental or quasi experimental studies conducted in high income countries. Studies of interest were retrieved from multidisciplinary database as well as health, economic, social sciences-specific literature browsers. Evidence of interest were summarised via narrative synthesis approach. Robustness of findings was assessed by tabulating impact by health outcome, type of intervention and study design. Overall, 18 relevant papers were identified, including 16 independent studies, one meta-analysis of randomized control trials (RCTs) and one pooled analysis of RCTs. Income-support interventions included: unconditional/conditional cash transfers, income tax credit, welfare to work, and minimum wage salary policies. Most studies were conducted in North America. Overall, the evidence suggested a positive, albeit small, effect of most policies on birth weight outcomes, but limited effect on mental health indicators. Results seemed to be robust to the type of intervention, but not to the study design, with RCTs consistently less likely to detect an impact. Given the large number of people targeted by these programs, one could infer that – despite small – the observed effect may be still relevant at population level. Nonetheless, the limited generalisability of the evidence gathered hampers firm conclusions. For the future, the breath and scope of this literature need to be broadened to fully exploit the potential of these interventions and understand how their public health impact can be maximised.
Associations between trajectories of obesity prevalence in English primary school children and the UK soft drink industry levy: an interrupted time series analysis of surveillance data
Authors: Rogers Nina T. , Cummins Steven , Forde Hannah , Jones Catrin P. , Mytton Oliver , Rutter Harry , Sharp Stephen J. , Theis Dolly , White Martin , Adams Jean
Published: September 2022

Background

Sugar sweetened beverages (SSBs) are the primary source of dietary added sugars in children, with high consumption commonly observed in more deprived areas where obesity prevalence is also highest. Associations between SSB consumption and obesity in children have been widely reported. In March 2016, a two-tier soft drinks industry levy (SDIL) on drinks manufacturers to encourage reformulation of SSBs in the UK was announced, and then implemented in April 2018. We examined trajectories in the prevalence of obesity at ages 4-5 years and 10-11 years, 19 months after the implementation of SDIL, overall and by sex and deprivation.

Methods and Findings

Data were from the National Child Measurement Programme and included annual repeat cross-sectional measurement of over one million children aged 4-5 and 10-11 years in state-maintained primary schools. Interrupted time series analysis of monthly obesity prevalence data from September 2013 to November 2019 was used to estimate absolute and relative changes in obesity prevalence compared to a counterfactual (adjusted for temporal variations in obesity prevalence) estimated from the trend prior to SDIL announcement. Differences between observed and counterfactual estimates were examined in November 2019 by age (4-5 or 10-11 years) and additionally by sex and deprivation quintile. In 10-11 year old children there was an overall absolute reduction in obesity prevalence (defined as >95thcentile on the UK90 growth charts) of 0.8% (95%CI: 0.3, 1.3). In 10-11 year old girls the reduction was 1.6% (95%CI: 1.1, 2.1), with greatest reductions in the two most deprived quintiles (e.g. there was an absolute reduction of 2.4% (95%CI: 1.6, 3.2) in prevalence of obesity in the most deprived quintile). In 10-11 year old boys, there was no change in obesity prevalence, except in the least deprived quintile where there was a 1.6% (95%CI: 0.7,2.5) absolute increase. In 4-5 year old children, relative to the counterfactual, there were overall increases in obesity prevalence in both genders (combined) and all deprivation quintiles except the most deprived where there was no change.

Conclusions

Our results suggest the SDIL was associated with decreased prevalence of obesity in 10-11 year old girls, with the greatest effects in those living in the most deprived areas. Additional strategies beyond SSB taxation will be needed to reduce obesity prevalence overall, and particularly in older boys and younger children.

Trial registration

ISRCTN18042742
Observing the self and other in motion modulates the excitability of vestibulocollic reflexes
Authors: Nakul Estelle , Deroualle Diane , Montava Marion , Lavieille Jean-Pierre , Lopez Christophe
Published: September 2022

Vestibular inputs from the inner ear are at the basis of the vestibulo-spinal and vestibulocollic reflexes involved in balance control. Studies have focused on how attentional load and emotions influence balance, but low-level social cues, such as observing human bodies in motion, have been neglected. Yet, individuals observing another person in a challenging posture or in motion can experience imbalance, indicating that sensorimotor resonance between self and others is involved. The present study examines how the observation of videos depicting human bodies in motion modulates well-established neurophysiological signatures of vestibular information processing. The excitability of vestibulocollic reflexes was assessed by analyzing the waveform of vestibular-evoked myogenic potentials (VEMPs) over the sternocleidomastoid and trapezius muscles of 25 healthy participants (13 females, 12 males). Here we show that observing human bodies undergoing passive whole-body rotations reduced the VEMPs amplitude when compared to observing an object. Importantly, the modulation depended on the person depicted in the video as VEMPs were reduced when observing oneself, compared to someone else being moved. Direction-specific effects and electromyography recordings ruled out non-specific emotional and attentional effects. These results show that the vestibular system is sensitive to observing human bodies in motion, establishing new connections between social neuroscience and vestibular neurophysiology.

Significance Statement

Vestibulocollic reflexes are thought to be consistent and of short latency. Yet, previous results show that observing conspecifics influences balance. We combined approaches from social neuroscience and vestibular electrophysiology to describe how the observation of self and other bodies in motion influences vestibular information processing. The results show that observing human bodies in motion reduces the amplitude of vestibulocollic reflexes involved in the stabilization of the head and balance. These results establish new relations between the sense of balance and social cognition and challenge classical views in vestibular neuroscience.
Metabotropic glutamate group II receptor activation in the dorsal striatum suppresses the motivation for cocaine in rats
Authors: Khoo Shaun Yon-Seng , Samaha Anne-Noël
Published: September 2022

After a history of intermittent cocaine intake, rats develop patterns of drug use characteristic of addiction. The dorsal striatum is involved in the increased pursuit of cocaine after intermittent drug self-administration experience. Within the dorsal striatum, chronic cocaine use changes metabotropic glutamate type II receptor (mGlu2/3) density and function. We examined the extent to which activity at these receptors mediates responding for cocaine after intermittent cocaine use. In Experiment 1, male Wistar rats (n = 11) self-administered 0.25 mg/kg/infusion cocaine during 10 daily intermittent access (IntA) sessions (5 min ON/25 min OFF, for 5 h/session). We then examined the effects of intra-dorsal striatum infusions of the mGlu2/3 receptor agonist LY379268 (0, 1, and 3 μg/hemisphere) on cocaine self-administration under a progressive ratio schedule of reinforcement. We observed a non-significant tendency for LY379268 to reduce responding for cocaine. In Experiment 2, we used a larger sample of male (n = 11) and female (n = 10) rats. Across 10 IntA sessions, the sexes showed similar levels of cocaine intake. Across the sexes, locomotion significantly increased over sessions, suggesting that rats developed psychomotor sensitization to self-administered cocaine. After 10 IntA sessions, intra-dorsal striatum LY379268 significantly reduced breakpoints achieved for cocaine, active lever presses, and cocaine infusions earned under progressive ratio. LY379268 had no effects on locomotion or inactive lever presses, indicating no motor effects. These results suggest that mGlu2/3 receptor activation in the dorsal striatum suppresses incentive motivation for cocaine, and this holds promise for anti-addiction therapeutics.
Purification and biochemical analysis of native AMPA receptors from three different mammalian species
Authors: Rao Prashant , Gouaux Eric
Published: September 2022

The majority of fast, excitatory synaptic transmission in the central nervous system (CNS) is mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), which are glutamate-activated ion channels integral to synaptic plasticity, motor coordination, learning, and memory. AMPARs are multiprotein assemblies comprised of a tetrameric receptor core that co-assembles with a broad range of peripheral auxiliary proteins which shape subcellular localization and signaling properties of the resulting complexes. Structure determination of AMPARs has traditionally relied on recombinant expression systems; however, these methods are not well suited to elucidate the diverse array of AMPAR assemblies that are differentially expressed in mammalian brains. While recent studies of native receptor complexes have advanced our understanding of endogenous assemblies, receptors thus far have only been isolated from rodent brain tissue. Here, we employed an immunoaffinity purification strategy to isolate native AMPARs from the brains of three different mammals - pigs, sheep, and cows. Compared to rodents; pigs, sheep, and cows are from a unique clade of mammals - ungulates, that share a closer genomic identity with humans. We determined the molecular size, overall yield, and purity of native AMPARs isolated from these three mammals, thereby demonstrating that structural determination and biochemical analysis is possible from a clade of mammals evolutionarily distinct from rodents.
Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA
Authors: Gigante Crystal M. , Plumb Matthew , Ruprecht Ali , Zhao Hui , Wicker Vaughn , Wilkins Kimberly , Matheny Audrey , Khan Theodora , Davidson Whitni , Sheth Mili , Burgin Alex , Burroughs Mark , Padilla Jasmine , Lee Justin S. , Batra Dhwani , Hetrick Ethan E. , Howard Dakota T. , Garfin Jacob , Tate Lisa , Hubsmith Shan J. , Mendoza Rafael M. , Stanek Danielle , Gillani Sarah , Lee Michelle , Mangla Anil , Blythe David , SierraPatev Sean , Carpenter-Azevedo Kristin , Huard Richard C. , Gallagher Glen , Hall Joshua , Ash Stephanie , Kovar Lynsey , Seabolt Matthew H. , Weigand Michael R. , Damon Inger , Satheshkumar Panayampalli S. , McCollum Andrea M. , Hutson Christina L. , Wang Xiong , Li Yu
Published: September 2022

Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3’ terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance.
Global genomic analysis reveals the genetic origin and secondary invasion of fall armyworm in the Eastern hemisphere
Authors: Zhang Lei , Li Zaiyuan , Peng Yan , Liang Xinyue , Wilson Kenneth , Chipabika Gilson , Karangwa Patrick , Uzayisenga Bellancile , Mensah Benjamin A. , Kachigamba Donald L. , Xiao Yutao
Published: September 2022

The major plant pest fall armyworm (FAW),Spodoptera frugiperda, is native to the Americas and has colonized African and Asian countries in the Eastern hemisphere since 2016, causing severe damage to multiple agricultural crop species. However, the genetic origin of these invasive populations require more in-depth exploration. We analyzed genetic variation across FAW genomes of 153 newly sequenced individuals from Eastern hemisphere and 127 individuals mostly originating from the Americas. The global genetic structure of FAW shows that the FAW in American has experienced deep differentiation, largely consistent with the Z-chromosomalTpihaplotypes commonly used to differentiate “corn-strain” and “rice-strain” populations. Results indicate that the invasive Eastern hemisphere populations are different from the American ones and have relatively homogeneous population structure, consistent with the common origin and recent spreading from Africa to Asia. Our analyses suggest that north-and central American “corn-strain” FAW are the most likely sources of the invasion into the Eastern hemisphere. Furthermore, evidence based on genomic, transcriptomic and mitochondrial haplotype network analysis suggest that there has been an earlier independent introduction of FAW into Africa that introgressed into the recent invasive population.
On the origin ofR2orientation dependence angle offsets in white matter
Authors: Pang Yuxi
Published: September 2022

Purpose

to identify the origin of confounding angle offsetε0inR2orientation dependence and to propose a novel framework for better characterizing anisotropicR2in brain white matter (WM).

Methods

Anisotropic (ε) rather than principal diffusivity direction (Φ) was theorized along axon fiber, withεdetermined by all eigenvalues and eigenvectors from diffusion tensor. An extra parameterε0was introduced into generalized magic angle effect function to account for any offset inR2orientation dependence derived fromT2-weighted image (b=0). These dependences referenced byεwere compared to those referenced as usual by Φ atb-values of 1000 and 2000 (s/mm2) on both linear and planar tensor image voxels in WM, based on public domain ultrahigh-resolution (760µm3) Connectome DTI datasets of a healthy young adult brain. A Student’s t-test was used to assess the mean differences and the statistical significance was considered atP< 0.05.

Results

Fittedε0became zero if referenced byεor nonzero if referenced by Φ, signifying the origin ofε0. Nonzeroε0relied onb-values and tensor shapes so did other model parameters, e.g., the amplitude of anisotropicR2(1/s) significantly increased when using a higherb-value for the linear tensor image voxels, i.e., 3.3±0.1 vs. 1.8±0.1,P< 0.01.

Conclusion

The origin ofR2orientation dependence angle offsets has been identified and the combined anisotropic diffusion and transverse relaxation models have fully quantifiedR2orientational anisotropies, thus providing novel insights otherwise unattainable on microstructural alterations in WM.
Antiviral effect of thiazolides relies on mitochondrial mild uncoupling
Authors: Hammad Noureddine , Ransy Céline , Pinson Benoit , Talmasson Jeremy , Bréchot Christian , Bouillaud Frédéric , Rossignol Jean-François
Published: September 2022

Background

Viruses are dependent on cellular energy metabolism for their replication, the drug Nitazoxanide (Alinia) was shown to interfere with both. An effect of Alinia on cellular energy metabolism is the uncoupling of mitochondrial oxidative phosphorylation (OXPHOS). Our hypothesis was that uncoupling grounds the antiviral properties of Alinia.

Methods

Alinia or an unrelated uncoupler were applied to a viral releasing cell line to obtain the same increasing levels of uncoupling hence identical interference with OXPHOS.

Findings

Decrease in infectious viral particles release reflected the intensity of interference irrespective of the nature of the drug and was significant with modest deviation (≤25%) from normal.

Interpretations

A mild interference on cellular energy metabolism impacts significantly on viral replication cycle. This would explain Alinia’s antiviral properties in vitro moreover antiviral action of Alinia is supported by clinical trials.

Perspectives

Altogether this indicates that moderate interference with mitochondrial bioenergetics should be considered as a ground for a therapeutic effect. In addition, Alinia would constitute example for a safe therapeutical use of an uncoupler, which deserves consideration for a wider range of applications.
Pan-cancer genomic analysis shows hemizygousPTENloss tumors are associated with immune evasion and poor outcome
Authors: Vidotto T , Melo CM , Lautert-Dutra W , Chaves LP , Reis RB , Squire JA
Published: September 2022

In tumors, somatic mutations of thePTENsuppressor gene are associated with advanced disease, chemotherapy resistance, and poor survival.PTENloss of function may occur by inactivating mutation, by deletion, either affecting one copy (hemizygous loss) leading to reduced gene expression or loss of both copies (homozygous) with expression absent. Various murine models have shown that minor reductions in PTEN protein levels strongly influence tumorigenesis. MostPTENbiomarker assays dichotomize PTEN (i.e. presence vs. absence) ignoring the role of one copy loss. We performed aPTENcopy number analysis of 9,793 TCGA cases from 30 different tumor types. There were 419 (4.28%) homozygous and 2484 (25.37%) hemizygousPTENlosses. Hemizygous deletions led to reduced PTEN gene expression, accompanied by increased levels of instability and aneuploidy across tumor genomes. Outcome analysis of the pan-cancer cohort showed that losing one copy ofPTENreduced survival to comparable levels as complete loss, and was associated with transcriptomic changes controlling immune response and the tumor microenvironment. Immune cell abundances were significantly altered forPTENloss, with changes in head and neck, cervix, stomach, prostate, brain, and colon more evident in hemizygous loss tumors. These data suggest that reduced expression ofPTENin tumors with hemizygous loss leads to tumor progression and influences anticancer immune response pathways.
Interactions between time on diet, antibiotic treatment, and liver abscess development on the fecal microbiome of beef cattle
Authors: Plata German , Baxter Nielson T , Hawkins Troy B , Huntimer Lucas , Nagireddy Akshitha , Susanti Dwi , Reinbold James B
Published: September 2022

Liver abscesses caused by polymicrobial infections of the liver are a widespread problem in feedlot cattle production. There are currently no effective methods for the early detection of liver abscesses or to predict antibiotic efficacy. Although gene expression and microbiome differences have been reported in the rumen of abscessed and normal animals, liver abscess biomarkers using less invasive tools can facilitate managing of the disease in the field. Here we report the results of two studies measuring the fecal microbiome composition of steers that did or did not develop liver abscesses, with or without antibiotic treatment, along a 7-month feeding period on a high-concentrate diet. Our results indicate a limited impact of liver abscesses or tylosin on fecal microbiome composition, with time on diet explaining most variance in the fecal microbiome. Interestingly, in both studies, antibiotic treatment led to larger differences in both the composition and variance of the fecal microbiomes between abscessed and normal animals compared to controls. These differences were limited to specific sampling times in each of the two studies. Although multiple amplicon sequence variants with differential abundances according to liver abscess state were identified, there was no overlap between the two studies. Our results suggests that early fecal biomarkers of liver abscess susceptibility might be developed, especially for animals receiving preventative antibiotics, but the fecal abundance of individual microorganisms may not be a robust predictor across different sampling times or diet regimes.
Computational remodeling of an enzyme conformational landscape for altered substrate selectivity
Authors: St-Jacques Antony D. , Rodriguez Joshua M. , Eason Matthew G. , Foster Scott M. , Khan Safwat T. , Damry Adam M. , Goto Natalie K. , Thompson Michael C. , Chica Roberto A.
Published: September 2022

Structural plasticity of enzymes dictates their function. Yet, our ability to rationally remodel enzyme conformational landscapes to tailor catalytic properties remains limited. Here, we report a computational procedure for tuning conformational landscapes that is based on multistate design. Using this method, we redesigned the conformational landscape of a natural aminotransferase to preferentially stabilize a less populated but reactive conformation, and thereby increase catalytic efficiency with a non-native substrate to alter substrate selectivity. Steady-state kinetics of designed variants revealed selectivity switches of up to 1900-fold, and structural analyses by room-temperature X-ray crystallography and multitemperature nuclear magnetic resonance spectroscopy confirmed that conformational equilibria favoured the target conformation. Our computational approach opens the door to the fine-tuning of enzyme conformational landscapes to create designer biocatalysts with tailored functionality.
Influenza virus membrane fusion is promoted by the endosome-resident phospholipid bis(monoacylglycero)phosphate
Authors: Mannsverk Steinar , Villamil Giraldo Ana M. , Kasson Peter M.
Published: September 2022

The phospholipid bis(monoacylglycero)phosphate (BMP) is enriched in late endosomal and endo-lysosomal membranes and is believed to be involved in membrane deformation and generation of intralumenal vesicles within late endosomes. Previous studies have demonstrated that BMP promotes membrane fusion of several enveloped viruses, but a limited effect has been found on influenza virus. Here, we report the use of single-virus fusion assays to dissect BMP’s effect on influenza virus fusion in greater depth. In agreement with prior reports, we found that hemifusion kinetics and efficiency were unaffected by the addition of 10-20 mol % BMP to the target membrane. However, using an assay for fusion pore formation and genome exposure, we found full fusion efficiency to be substantially enhanced by the addition of 10-20 mol % BMP to the target membrane, while the kinetics remained unaffected. By comparing BMP to other negatively charged phospholipids, we found the effect on fusion efficiency mainly attributable to headgroup charge, although we also hypothesize a role for BMP’s unusual chemical structure. Our results suggest that BMP function as a permissive factor for a wider range of viruses than previously reported. We hypothesize that BMP may be a general co-factor for endosomal entry of enveloped viruses.
Antigenic characterisation of human monoclonal antibodies for therapeutic use against H7N9 avian influenza virus
Authors: Chang Pengxiang , Lukosaityte Deimante , Sealy Joshua E. , Rijal Pramila , Sadeyen Jean-Remy , Bhat Sushant , Crossley Sylvia , Daines Rebecca , Huang Kuan-Yin A. , Townsend Alain R. , Iqbal Munir
Published: September 2022

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1500 human deaths and millions of poultry culling. Despite large-scale poultry vaccination, H7N9 AIVs continue to circulate among poultry in China and pose a threat to human health. Previously, we isolated and generated four monoclonal antibodies (mAbs) derived from humans naturally infected with H7N9 AIV. Here, we investigated the haemagglutinin (HA) epitopes of H7N9 AIV targeted by these mAbs (L3A-44, K9B-122, L4A-14 and L4B-18) using immune escape studies. Our results revealed four key antigenic epitopes at HA amino acid positions 125, 133, 149, and 217. The mutant H7N9 viruses representing escape mutations containing Alanine to Threonine at residue 125 (A125T), Glycine to Glutamic acid at residue 133 (G133E), Asparagine to Aspartic acid at residue 149 (N149D), or Leucine to Glutamine at residue 217 (L217Q) showed reduced or completely abolished cross-reactivity with the mAbs, as measured by hemagglutination inhibition (HI) assay. We further assessed the potential risk of these mutants to humans should they emerge following mAb treatment by measuring the impact of these HA mutations on virus fitness and evasion of host adaptive immunity. Here we showed that the L4A-14 mAb had broad neutralizing capability, and its escape mutant N149D had reduced viral stability and human receptor binding and could be neutralized by both post-infection and antigen-induced sera. Therefore, L4A-14 mAb could be a therapeutic candidate for H7N9 AIV infection in humans and warrants further investigation for therapeutic application.

IMPORTANCE

Avian Influenza virus (AIV) H7N9 continues to circulate and evolve in birds, posing a credible threat to humans. Antiviral drugs have been proven useful for the treatment of severe influenza infections in humans, however, concerns have been raised as antiviral resistant mutants have emerged. Monoclonal antibodies (mAbs) have been studied for both prophylactic and therapeutic applications in infectious disease control and have demonstrated great potential. For example, mAb treatment has significantly reduced the risk of people developing severe disease with SARS-COV 2 infection. In addition to the protection efficiency, we should also consider the potential risk of the escape mutants generated by mAb treatment to public health by assessing their viral fitness and potential to compromise host adaptive immunity. Considering these parameters, we assessed four human mAbs derived from humans naturally infected with H7N9 AIV and showed that the mAb L4A-14 displayed potential as a therapeutic candidate.
Dorsolateral Prefrontal Cortex Metabolic Profiles in Autism Spectrum Disorder Correlate Atypically with Nonverbal IQ and Typically with Attention Switching
Authors: Weerasekera Akila , Ion-M□rgineanu Adrian , McGuiggan Nicole M. , Shetty Nandita , Joseph Robert M. , Ghosh Shantanu , Alshikho Mohamad , Herbert Martha R. , Kenet Tal , Ratai Eva-Maria
Published: September 2022

Background

The neurometabolic profile of associated with autism spectrum disorder (ASD) has been reported to be abnormal by some studies showing region specific metabolite levels in ASD, while others report no group differences. The neurometabolic profile of the left dorsolateral prefrontal cortex (DLPFC) is of particular interest due to the DLPFC relevance to cognitive and executive function, and to ASD.

Method

We used 1H-MRS to investigate neurometabolic profiles in the DLPFC of ASD and sex/IQ-matched typically developing (TD) children (ages 9-13). We focused on levels of Glutamate and Glutamine (Glx) due to many reported Glx abnormalities ASD, and of Choline (Cho) because of its relationship to intelligence quotient (IQ) and to attentional re-orienting difficulties.

Results

While no significant group differences were observed in absolute concentrations, metabolite levels were correlated with the behavioral phenotype of ASD children. In the ASD group but not the TD group, nonverbal IQ (NVIQ) was negatively associated with Cho (r=-0.59, p=0.026) and positively associated with Glx/Cr (r=0.66, p=0.011). Furthermore, attentional-switching scores in the ASD group correlated negatively with Cho (r=-0.69, p=0.009), and positively with Glx/Cr for both the ASD (r=0.73, p=0.004) and TD (r=0.54, p=0.040) groups.

Conclusions

Cho and Glx/Cr have different neurometabolic roles in modulating NVIQ in ASD compared to TD children, while their role in attentional switching seems preserved in ASD. Elucidating the apparently divergent role of neurometabolites in ASD in the absence of significant group differences in absolute levels is an important step towards understanding and mapping the neural correlates of ASD. These results are also relevant in the context of the significant cognitive function heterogeneity associated with the ASD phenotype, as they suggest possible underlying neural mechanisms that do not overlap which those expected from typical development.
Chaperonin activity of Plasmodium prefoldin complex is essential to guard proteotoxic stress response and presents a new target for drug discovery
Authors: Shoaib Rumaisha , Kumar Vikash , Garg Swati , Saini Monika , Kumari Jyoti , Maurya Preeti , Gupta Aashima , Gupta Nutan , Singh Harshita , Verma Pritee , Jain Ravi , Biswas Shreeja , Behl Ankita , Abid Mohammad , Singh Shailja
Published: September 2022

The intraerythrocytic growth of malaria parasite is challenged by the presence of proteotoxic stress and intrinsically unstructured proteins in the cytoplasm due to formation of toxic heme during haemoglobin digestion. To overcome the unavoidable stress and maintain the cellular protein homeostasis, parasite encodes for a number of chaperones and co-chaperones. Here, we functionally characterize the Plasmodium falciparum prefoldins (PfPFD1-6), a hexameric co-chaperone complex, for their role in protein homeostasis. We demonstrate that PfPFD1-6 localise to cytosol of the parasite and the subunits perform an orchestrated interaction (-PFD3-PFD2-PFD1-PFD5-PFD6-PFD4-) to form an active jelly-fish like complex. Biperiden, an N-propylpiperidine analogue identified by chemotype search from FDA, strongly binds and restricts the formation of prefoldin complex and inhibited its interaction with the substrates, PfMSP-1 and α-tubulin-I. Biperiden treatment potently inhibited the in vitro (IC50: 1μM) and in vivo growth of malaria parasite. Thus, this study provides novel virtues towards understanding the role of PfPFDs in regulating protein homeostasis and opens new avenues for drug discovery against malaria.
scRNA-Seq-based drug repurposing targeting idiopathic pulmonary fibrosis (IPF)
Authors: Liu Anika , Lee Joo-Hyeon , Han Namshik , Bender Andreas
Published: September 2022

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease, which affects around three million people worldwide and is characterized by impaired regeneration from recurrent injury to the alveolar epithelium resulting in progressive lung scarring. In this work, we target a cell transition in the differentiation of AT2 cells into mature AT1 cells which is inhibited in IPF and contributes to the regeneration of the alveolar epithelium. We hypothesize that inducing this transition promotes lung regeneration and can ameliorate the disease. To this end, we characterized the intermediate population to AT1 cell transition signature using multiple recently generated single-cell RNA-Seq datasets on murine bleomycin injury and IPF patients. We then matched this signature to drug perturbation signatures retrieved from the LINCS database to identify the most suitable candidates for drug repurposing. Compound classes identified in this analysis include glucocorticoids, HSP90 inhibitors, HDAC inhibitors and a range of kinase inhibitors. Furthermore, we are able to interpret our findings by identifying multiple potential direct targets and downstream effectors, such as NFKB1 and HIF1A. Overall, we show how scRNA-Seq data can potentially be leveraged for drug repurposing by enabling better characterization of cell transitions which can subsequently be used for signature matching.
Sub-Saharan Africa's rising public debt stock: before another debt relief!
Authors: Olaoye Olumide
Published: September 2022

Purpose

In light of the recent calls for another round of debt relief for African countries, by African finance ministers and governments, the aim of the study is twofold. First, the study examined the effect of public debt on macroeconomic performance. Two, the study also examined whether previous debt relief has impacted positively on sub-Saharan African economies.

Design/methodology/approach

The study adopts the two-step system GMM that accounts for potential endogeneity and feedback effect in dynamic panel models. As robustness, the study performs the two-stage least square (2SLS) estimation method.

Findings

The study reveals that previous debt relief programmes only had a marginal effect on economic growth in the region. The study found that corruption impacts negatively on the effectiveness of debt relief to achieve the desired economic outcomes. The study also found that sub-Saharan African economies seem to have shifted away from traditional concessional sources of financing towards market-based lenders dominated by China.

Originality/value

The study adds to the growing evidence in the public debt literature by looking at the separate impact of domestic and foreign debts on macroeconomic indicators of economic growth, inflation, unemployment and exchange rate. The study also controlled for previous debt relief in light of the call for another round of debt relief.

Graphical Abstract
Sustaining modern heritage buildings: visual defect categorisation guides for the general condition survey of rendered-painted facades
Authors: Ertemir Dilruba Yağmur , Edis Ecem
Published: September 2022

Purpose

Regular inspection and maintenance is recommended to preserve and sustain built cultural heritage. Systematising inspection processes and knowledge on defects, and providing pictorial guides for evaluating defects is an approach that may facilitate their condition survey. Generating pictorial guides for preliminary visual inspection of Modern Heritage buildings with rendered-painted facade concerning two defects (i.e. crack and efflorescence) is aimed in this study. These guides are thought as aids in determining the defect levels and deciding the necessity of advanced examination and/or maintenance. Analysing briefly the evolution of crack over time in the inspected buildings under environmental conditions of Istanbul (Turkey) is also aimed.

Design/methodology/approach

Preliminary guide generation was based mainly on literature survey on defects, and visual data collection from eight Modern Movement examples in Istanbul. The guides were then refined through systematic visual inspection of three buildings among them. Evolution of crack over time was analysed through a second inspection performed after 2.5 years.

Findings

Visual inspections showed that crack is the commonest defect occurring mostly on projecting structural members, while efflorescence is less in number. Comparison of cracks' visuals taken in the first and second inspections showed that deterioration process is slow.

Originality/value

Modern heritage buildings usually have some characteristic features, which may sometimes lead to accumulation of defects at certain locations or may lead to formation of certain defects. Generating visual guides as a start for an initiative for a comprehensive defects catalogue particular for Modern Movement buildings in line with associated cultural heritage standards may contribute to their preservation by easing the condition surveys.
Citizen involvement in digital transformation: a systematic review and a framework
Authors: Liu Caihua , Zowghi Didar
Published: September 2022

Purpose

The purpose of this paper is to improve the understanding of the factors influencing the success of digital transformation (DT) and problems/challenges in DT as well as the communication methods used to involve citizens, based on a systematic literature review of research articles about citizen involvement in DT published between January 2010 and May 2021.

Design/methodology/approach

After establishing inclusion and exclusion criteria, a systematic review of relevant studies was conducted. Out of a total of 547 articles, 33 met the paper selection criteria.

Findings

The analysis of the included 33 empirical studies reveals that the factors influencing the success of DT can be described as the opposite side from challenges and problems in DT. These factors and challenges/problems all influence DT and they can be grouped into organisational values, management capabilities, organisational infrastructure, and workforce capabilities. The communication methods for citizen involvement in DT include: (1) communication mediated by human, (2) communication mediated by computers, and (3) mixed communication methods.

Originality/value

The study identified specific factors that influence DT supported by citizen involvement, at a more fine-grained level. The findings concerning communication methods extend related studies for citizen involvement by adding town hall meetings and communication methods mediated by computers. Furthermore, this study links the research findings to develop a framework for citizen involvement in DT, assisting in better selecting communication methods to involve citizens for addressing problem areas in DT.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/OIR-04-2022-0237
Widespread yet persistent low abundance of TIM5‐like cyanophages in the oceans
Authors: Baran Nava , Carlson Michael C. G. , Sabehi Gazalah , Peleg Margalit , Kondratyeva Kira , Pekarski Irena , Lindell Debbie
Published: September 2022

Ocean ecosystems are inhabited by a diverse set of viruses that impact microbial mortality and evolution. However, the distribution and abundances of specific viral lineages, particularly those from the large bank of rare viruses, remains largely unknown. Here, we assessed the diversity and abundance of the TIM5‐like cyanophages. The sequencing of three new TIM5‐like cyanophage genomes and environmental amplicons of a signature gene from the Red Sea revealed highly conserved gene content and sequence similarity. We adapted the polony method, a solid‐phase polymerase chain reaction assay, to quantify TIM5‐like cyanophages during three 2000 km expeditions in the Pacific Ocean and four annual cycles in the Red Sea. TIM5‐like cyanophages were widespread, detected at all latitudes and seasons surveyed throughout the photic zone. Yet they were generally rare, ranging between <100 and 4000 viruses·ml−1. Occasional peaks in abundance of 10‐ to 100‐fold were observed, reaching 71,000 viruses·ml−1. These peaks were ephemeral and seasonally variable in the Red Sea. Infection levels, quantified during one such peak, were very low. These characteristics of low diversity and abundance, as well as variable outbreaks, distinguishes the TIM5‐like lineage from other major cyanophage lineages and illuminates that rare virus lineages can be persistent and widespread in the oceans.
Reciprocal exchange, value, and forms of transaction: an archaeological approach from the Atacama Desert (northern Chile)
Authors: Gallardo Francisco
Published: September 2022

Exotic goods belong to a class of valuable materials that have played an important role in ritual activities, political ceremonies, and economic agreements in different human contexts, both past and present. However, we have made little progress in understanding exchanges as relationships between donors and receivers, as forms of reciprocal interaction that forged a network of links between individuals and groups of different cultural traditions. Although the archaeological record presents multiple limitations in the study of these interactions, an exploratory archaeological perspective allows researchers to examine questions related to the social character of exchanges, the value attributed to goods, and the ways in which these circulated. I argue that the presence of exotic goods is an indicator of intercultural social relations whose values are expressed through their consumption. They represent a relational materiality between humans and nonhumans, which allows us to discuss forms of reciprocity and the cultural nature of the network of long‐distance exchanges. Here, I present case studies from archaeological localities in the Atacama Desert (northern Chile) during the Formative Period (800 BCE‐400 CE) to illustrate these concepts.
Textual Analysis in Accounting: What's Next?*
Authors: Bochkay Khrystyna , Brown Stephen V. , Leone Andrew J. , Tucker Jennifer Wu
Published: September 2022

Natural language is a key form of business communication. Textual analysis is the application of natural language processing (NLP) to textual data for automated information extraction or measurement. We survey publications in top accounting journals and describe the trend and current state of textual analysis in accounting. We organize available NLP methods in a unified framework. Accounting researchers have often used textual analysis to measure disclosure sentiment, readability, and disclosure quantity; to compare disclosures to determine similarities or differences; to identify forward‐looking information; and to detect themes. For each of these tasks, we explain the conventional approach and newer approaches, which are based on machine learning, especially deep learning. We discuss how to establish the construct validity of text‐based measures and the typical decisions researchers face in implementing NLP models. Finally, we discuss opportunities for future research. We conclude that (i) textual analysis has grown as an important research method and (ii) accounting researchers should increase their knowledge and use of machine learning, especially deep learning, for textual analysis.
Evaluation of the effects of different chelation agents on root dentin roughness
Authors: Atalay Işınsu , Erişen Fehmi Raif
Published: September 2022

Successful root canal treatment requires effective irrigation of the entire root canal system. While chelating agents support irrigation, they can also alter physicochemical properties of the root dentin structure. The aim of this study is to evaluate the effect of different chelation agents on root dentin roughness. Twenty‐five extracted maxillary incisors were used in this study. Samples were separated longitudinally and divided into five groups: distilled water, NaOCl, ethylenediaminetetraacetic acid (EDTA), phytic acid and citric acid (CA). Atomic force microscope and energy dispersive X‐ray spectroscopy analyses were used for analysing. One‐way analysis of variance and Turkey tests were used in the statistical analysis of the study. EDTA, CA and phytic acid solutions increased the roughness and phytic acid and CA solutions decreased the Ca/P ratio in dentin tissue. No statistical difference was observed in the other groups. The decrease of Ca/P ratio should be taken under consideration during irrigation. The increase in surface roughness may provide clinical benefit by supporting the adhesion of the root canal filling materials to the dentin surface.