bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal dynamics of neural responses in human visual cortex
Authors: Groen Iris I.A. , Piantoni Giovanni , Montenegro Stephanie , Flinker Adeen , Devore Sasha , Devinsky Orrin , Doyle Werner , Dugan Patricia , Friedman Daniel , Ramsey Nick , Petridou Natalia , Winawer Jonathan
Published: August 2021

Neural responses to visual stimuli exhibit complex temporal dynamics, including sub-additive temporal summation, response reduction with repeated or sustained stimuli (adaptation), and slower dynamics at low contrast. These phenomena are often studied independently. Here, we demonstrate these phenomena within the same experiment and model the underlying neural computations with a single computational model. We extracted time-varying responses from electrocorticographic (ECoG) recordings from patients presented with stimuli that varied in contrast, duration, and inter-stimulus interval (ISI). Aggregating data across patients yielded 98 electrodes with robust visual responses, covering both earlier (V1-V3) and higher-order (V3a/b, LO, TO, IPS) retinotopic maps. In all regions, the temporal dynamics of neural responses exhibit several non-linear features: peak response amplitude saturates with high contrast and longer stimulus durations; the response to a second stimulus is suppressed for short ISIs and recovers for longer ISIs; response latency decreases with increasing contrast. These features are accurately captured by a computational model comprised of a small set of canonical neuronal operations: linear filtering, rectification, exponentiation, and a delayed divisive normalization. We find that an increased normalization term captures both contrast- and adaptation-related response reductions, suggesting potentially shared underlying mechanisms. We additionally demonstrate both changes and invariance in temporal response dynamics between earlier and higher-order visual areas. Together, our results reveal the presence of a wide range of temporal and contrast-dependent neuronal dynamics in the human visual cortex, and demonstrate that a simple model captures these dynamics at millisecond resolution.

Significance Statement

Sensory inputs and neural responses change continuously over time. It is especially challenging to understand a system that has both dynamic inputs and outputs. Here we use a computational modeling approach that specifies computations to convert a time-varying input stimulus to a neural response time course, and use this to predict neural activity measured in the human visual cortex. We show that this computational model predicts a wide variety of complex neural response shapes that we induced experimentally by manipulating the duration, repetition and contrast of visual stimuli. By comparing data and model predictions, we uncover systematic properties of temporal dynamics of neural signals, allowing us to better understand how the brain processes dynamic sensory information.
Integrated single-cell transcriptomic and epigenetic analyses of cell-state transition and lineage commitment in the embryonic mouse cerebellum
Authors: Khouri-Farah Nagham , Guo Qiuxia , Morgan Kerry , Shin Jihye , Li James Y.H.
Published: August 2021

Recent studies using single-cell RNA-seq have revealed cellular heterogeneity in the developing mammalian cerebellum, yet the regulatory logic underlying this cellular diversity remains to be elucidated. Using integrated single-cell RNA and ATAC analyses, we resolved developmental trajectories of cerebellar progenitors and identified putative trans- and cis- elements that control cell state transition. We reverse-engineered gene regulatory networks (GRNs) of each cerebellar cell type. Through in silico simulations and in vivo experiments, we validated the efficacy of GRN analyses and uncovered the molecular control of a newly identified stem zone, the posterior transitory zone (PTZ), which contains multipotent progenitors for granule neurons, Bergmann glia, and choroid plexus epithelium. Importantly, we showed that perturbing cell fate specification of PTZ progenitors causes posterior cerebellar vermis hypoplasia, the most common cerebellar birth defect in humans. Our study provides a foundation for comprehensive studies of developmental programs of the mammalian cerebellum.
The epigenetic evolution of gliomas is determined by their IDH1 mutation status and treatment regimen
Authors: Malta Tathiane M , Sabedot Thais S , Datta Indrani , Garofano Luciano , Vallentgoed Wies , Varn Frederick S , Aldape Kenneth , D’Angelo Fulvio , Bakas Spyridon , Barnholtz-Sloan Jill S , Gan Hui K , Hasanain Mohammad , Hau Ann-Christin , Johnson Kevin C , Khasraw Mustafa , Kocakavuk Emre , Kouwenhoven Mathilde CM , Migliozzi Simona , Niclou Simone P , Niers Johanna M , Ormond D. Ryan , Paek Sun Ha , Reifenberger Guido , Sillevis Smitt Peter A , Smits Marion , Stead Lucy F , van den Bent Martin J , Van Meir Erwin G , Walenkamp Annemiek , Weiss Tobias , Weller Michael , Westerman Bart A , Ylstra Bauke , Wesseling Pieter , Lasorella Anna , French Pim J , Poisson Laila M ,   The GLASS Consortium, Verhaak Roel GW , Iavarone Antonio , Noushmehr Houtan
Published: August 2021

Tumor adaptation or selection is thought to underlie therapy resistance of gliomas. To investigate the longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 143 matched initial and recurrent patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) gliomas. IDHwt gliomas showed a longitudinally stable epigenome with relatively low levels of global methylation, whereas the epigenome of IDHmut gliomas showed initial high levels genome-wide of DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. By integrating DNA methylation and gene expression data, adaptive changes of putative master regulators of the cell cycle and of differentiation were seen in IDHmut recurrent tumors. Furthermore, relapses of IDHmut tumors were accompanied by histological progression which in turn influenced survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment differed between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment for IDHmut gliomas. Our study provides one of the largest cohorts of paired glioma samples profiled with epigenomics, transcriptomics and genomics; and our results demonstrate that the treatment of IDHmut gliomas reshapes the epigenome towards an IDHwt-like phenotype. Accordingly, the prevalent practice of early genotoxic treatment in this patient population may need to be revisited.
Single-molecule simultaneous profiling of DNA methylation and DNA-protein interactions with Nanopore-DamID
Authors: Cheetham Seth W. , Jafrani Yohaann M. A. , Andersen Stacey B. , Jansz Natasha , Kindlova Michaela , Ewing Adam D. , Faulkner Geoffrey J.
Published: August 2021

We present Nanopore-DamID, a method to simultaneously detect cytosine methylation and DNA-protein interactions from single molecules, via selective sequencing of adenine-labelled DNA. Assaying LaminB1 and CTCF binding with Nanopore-DamID, we identify escape from LAD-associated repression of hypomethylated promoters amidst generalised hypermethylation of LaminB1-associated regulatory elements. We detect novel CTCF binding sites in highly repetitive regions, and allele-specific CTCF binding to imprinted genes and the active X chromosome. Nanopore-DamID highlights the importance of DNA methylation to transcription factor activity.
The Role of Low Molecular Weight Fungal Metabolites in Grapevine Trunk Disease Pathogenesis: Eutypa Dieback and Esca
Authors: Perez-Gonzalez Gabriel , Sebestyen Dana , Petit Elsa , Jellison Jody , Mugnai Laura , Gelhaye Eric , Lee Norman , Farine Sibylle , Bertsch Christophe , Goodell Barry
Published: August 2021

Eutypa dieback and Esca are serious grapevine trunk diseases (GTDs) caused by fungal consortia causing large economic losses in vineyards. Depending on the disease the species involved include Eutypa lata, Phaeoacremonium minimum, and Phaeomoniella chlamydospora. There is a need to understand the complex pathogenesis mechanisms used by these fungi to develop treatments for the diseases they cause. Low molecular weight metabolites (LMW) are known to be involved in non-enzymatic oxygen radical generation in fungal degradation of wood by some Basidiomycota species, and as part of our work to explore the basis for fungal consortia pathogenesis, LMW metabolite involvement by the causal GTD fungi was explored. The GTD fungal pathogens examined, E. lata, P. minimum and P. chlamydospora, were found to produce low molecular weight iron binding metabolites that preferentially reduced iron or redox cycled to produce hydrogen peroxide. Uniquely, different LMW metabolites isolated from the GTD fungi promoted distinct chemistries that are important in a type of non-enzymatic catalysis known as chelator-mediated Fenton (CMF) reactions. CMF chemistry promoted by LMW metabolites from these fungi allowed for the generation of highly reactive hydroxyl radicals under conditions promoted by the fungi. We hypothesize that this new reported mechanism may help to explain the necrosis of woody grapevine tissue as a causal mechanism important in pathogenesis in these two grapevine trunk diseases.
The COVID-19 Pandemic and Early Child Cognitive Development: A Comparison of Development in Children Born During the Pandemic and Historical References
Authors: Deoni Sean CL , Beauchemin Jennifer , Volpe Alexandra , D’Sa Viren ,   the RESONANCE Consortium
Published: August 2021

Objective

To characterize cognitive function in young children under 3 years of age over the past decade, and test whether children exhibit different cognitive development profiles through the COVID-19 pandemic.

Study Design

Neurocognitive data (Mullen Scales of Early Learning, MSEL) were drawn from 700 healthy and neurotypically developing children between 2011 to 2021 without reported positive tests or clinical diagnosis of SARS-CoV-2 infection. We compared MSEL composite measures (general cognition, verbal, and non-verbal development) to test if those measured during 2020 and 2021 differed significantly from historical 2011-2019 values. We also compared MSEL values in a sub-cohort comprising infants 0-16 months of age born during the pandemic vs. infants born prior. In all analyses, we also included measures of socioeconomic status, birth outcome history, and maternal stress.

Results

A significant decrease in mean population MSEL measures was observed in 2021 compared to historical references. Infants born during the pandemic exhibited significantly reduced verbal, non-verbal, and overall cognitive performance compared to children born pre-pandemic. Maternal stress was not found to be associated with observed declines but a higher socioeconomic status was found to be protective.

Conclusions

Results reveal a striking decline in cognitive performance since the onset of the COVID-19 pandemic with infants born since mid-2020 showing an average decrease of 27-37 points. Further work is merited to understand the underlying causative factors.
COVID-19 vaccine acceptance among healthcare workers in India: Results from a cross-sectional survey
Authors: Mehta Kayur , Dhaliwal Baldeep K. , Zodpey Sanjay , Loisate Stacie , Banerjee Preetika , Gupta Madhu , Shet Anita
Published: August 2021

Background

Remarkable scientific progress has enabled expeditious development of effective vaccines against COVID-19. While healthcare workers (HCWs) have been at the frontlines for the pandemic response, vaccine acceptance amongst them needs further study.

Methods

A web-based survey to assess vaccine acceptance and preparedness in India was disseminated to HCWs working in various settings between January and February 2021, shortly after the launch of India’s vaccination campaign. Descriptive statistics were used to examine respondent demographics and Likert scale responses. Binomial logistic regression analyses were used to identify factors associated with vaccine acceptance.

Results

The survey yielded 624 respondents from 25 states and five union territories in India; 53.5% were male, and median age was 37 years (IQR 32-46). Amongst all respondents, 84.1% (525/624) supported COVID-19 vaccines, and 63.2% (141/223) of those unvaccinated at the time of survey administration were willing to accept a vaccine. Reliability on government sources, healthcare providers or scientific journal articles for COVID-19 related information was reported by 66.8%, while confidence in social media for this information was reported by only 4.5%. Factors independently associated with vaccine acceptance included advancing age (aOR 3.50 [95% CI, 1.04-11.76] for those above 45 years), evidence of vaccine effectiveness and safety (aOR 3.78 [95% CI 1.15-12.38]), and provision of free/no-cost vaccine (aOR 2.63 [95% CI, 1.06-6.50]). Most respondents (80%) were confident about their hospital being equipped to efficiently rollout COVID-19 vaccines to the general population.

Conclusions

Overall attitudes towards COVID-19 vaccination and preparedness were positive among HCWs in India, although acceptance was lower among healthier and younger HCWs. Data availability on vaccine safety and effectiveness, and cost considerations were important for acceptance. Targeted interventions are needed to improve vaccine acceptance amongst HCWs, since they are critical in promoting vaccine acceptance amongst the general population.
HDAC9structural variants disruptingTWIST1transcriptional regulation lead to craniofacial and limb malformations
Authors: Hirsch Naama , Dahan Idit , D’haene Eva , Avni Matan , Vergult Sarah , Vidal-García Marta , Magini Pamela , Graziano Claudio , Severi Giulia , Bonora Elena , Nardone Anna Maria , Brancati Francesco , Fernández-Jaén Alberto , Rory Olson J. , Hallgrimsson Benedikt , Birnbaum Ramon Y.
Published: August 2021

Structural variants (SVs) can affect protein-coding sequences as well as gene regulatory elements. However, SVs disrupting protein-coding sequences that also function as cis-regulatory elements remain largely uncharacterized. Here, we show that craniosynostosis patients with SVs containing the Histone deacetylase 9 (HDAC9) protein-coding sequence are associated with disruption ofTWIST1regulatory elements that reside withinHDAC9sequence. Based on SVs within theHDAC9-TWIST1locus, we defined the 3’ HDAC9 sequence (~500Kb) as a criticalTWIST1regulatory region, encompassing craniofacialTWIST1enhancers and CTCF sites. Deletions of eitherTwist1enhancers (eTw5-7Δ/Δ) or Ctcf site (CtcfΔ/Δ) within the Hdac9 protein-coding sequence in mice led to decreasedTwist1expression and altered anterior\posterior limb expression patterns of Shh pathway genes. This decreased Twist1 expression results in a smaller sized and asymmetric skull and polydactyly that resemblesTwist1+/-mouse phenotype. Chromatin conformation analysis revealed thatthe Twist1promoter region interacts withHdac9sequences that encompassTwist1enhancers and a Ctcf site and that interactions depended on the presence of both regulatory regions. Finally, a large inversion of the entireHdac9sequence (Hdac9INV/+) in mice that does not disruptHdac9expression but repositionsTwist1regulatory elements showed decreasedTwist1expression and led to a craniosynostosis-like phenotype and polydactyly. Thus, our study elucidated essential components ofTWIST1transcriptional machinery that reside within theHDAC9sequence, suggesting that SVs, encompassing protein-coding sequence, such asHDAC9, could lead to a phenotype that is not attributed to its protein function but rather to a disruption of the transcriptional regulation of a nearby gene, such asTWIST1.
An ultrapotent neutralizing bispecific antibody with broad spectrum against SARS-CoV-2 variants
Authors: Zhang Hui , Huang Haohui , Li Rong , Zhang Lu , Wang Zhiwei , Li Jiaping , Chen Junyou , Su Huafei , Zheng Dandan , Su Ziqi , Wang Li , Deng Chunping , Pei shujun , Zhu Shenghua , Li Chan , Yuan Yaochang , Yue Haitao , Wang Yanqun , Li Xiaobo , Liu Cuihua , Yu Jinchen , Zhang Hui , Li Shengfeng , Huang Xianming
Published: August 2021

In spite of the successful development of effective countermeasures against Covid-19, variants have and will continue to emerge that could compromise the efficacy of currently approved neutralizing antibodies and vaccines. Consequently, novel and more efficacious agents are urgently needed. We have developed a bispecific antibody, 2022, consisting of two antibodies, 2F8 and VHH18. 2F8 was isolated from our proprietary fully synthetic human IDEAL (Intelligently Designed and Engineered Antibody Library)-VH/VL library and VHH18 is a single domain antibody isolated from IDEAL-nanobody library. 2022 was constructed by attaching VHH18 to the C-terminal of Fc of 2F8. 2022 binds two non-overlapping epitopes simultaneously on the RBD of the SARS-CoV-2 spike protein and blocks the binding of RBD to human angiotensin-converting enzyme 2 (ACE2). 2022 potently neutralizes SARS-CoV-2 and all of the variants tested in both pseudovirus and live virus assays, including variants carrying mutations known to resist neutralizing antibodies approved under EUA and that reduce the protection efficiency of current effective vaccines. The half-maximum inhibitory concentration (IC50) of 2022 is 270 pM, 30 pM, 20 pM, and 1 pM, for wild-type, alpha, beta, and delta pseudovirus, respectively. In the live virus assay, 2022 has an IC50 of 26.4 pM, 13.3 pM, and 88.6 pM, for wild-type, beta, and delta live virus, respectively. In a mouse model of SARS-CoV-2, 2022 showed strong prophylactic and therapeutic effects. A single administration of 2022 intranasal (i.n.) or intraperitoneal (i.p.) 24 hours before virus challenge completely protected all mice from bodyweight loss, as compared with up to 20% loss of bodyweight in placebo treated mice. In addition, the lung viral titers were undetectable (FRNT assay) in all mice treated with 2022 either prophylactically or therapeutically, as compared with around 1×105pfu/g lung tissue in placebo treated mice. In summary, bispecific antibody 2022 showed potent binding and neutralizing activity across a variety of SARS-CoV-2 variants and could be an attractive weapon to combat the ongoing waves of the COVID-19 pandemic propagated mainly by variants, especially, the much more contagious delta variant.
Laterally transferred macrophage mitochondria act as a signaling source promoting cancer cell proliferation
Authors: Kidwell Chelsea U. , Casalini Joseph R. , Pradeep Soorya , Scherer Sandra D. , Greiner Daniel , Johnson Jarrod S. , Olson Gregory S. , Rutter Jared , Welm Alana L. , Zangle Thomas A. , Roh-Johnson Minna
Published: August 2021

Lateral transfer of mitochondria occurs in many physiological and pathological conditions. Given that mitochondria provide essential energy for cellular activities, mitochondrial transfer is currently thought to promote the rescue of damaged cells. We report that mitochondrial transfer occurs between macrophages and breast cancer cells, leading to increased cancer cell proliferation. Unexpectedly, transferred macrophage mitochondria are dysfunctional, lacking mitochondrial membrane potential. Rather than performing essential mitochondrial activities, transferred mitochondria accumulate reactive oxygen species which activates ERK signaling, indicating that transferred mitochondria act as a signaling source that promotes cancer cell proliferation. We also demonstrate that pro-tumorigenic M2-like macrophages exhibit increased mitochondrial transfer to cancer cells. Collectively, our findings reveal how mitochondrial transfer is regulated and leads to sustained functional changes in recipient cells.

One-Sentence Summary

Lateral transfer of macrophage mitochondria acts as a ROS signaling source, regulating cancer cell proliferation through ERK signaling.
Liver Organoid and T Cell Coculture Models Cytotoxic T Cell Responses against Hepatitis C Virus
Authors: Natarajan Vaishaali , Simoneau Camille R , Erickson Ann L , Meyers Nathan L , Baron Jody L , Cooper Stewart , McDevitt Todd C , Ott Melanie
Published: August 2021

Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV sincein vivoanimal models are limited andin vitrocancer cell models often show dysregulated immune and proliferative responses. Here we developed a CD8+T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV nonstructural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8+T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in anin vitrosetting using primary human cells.
Quality-preserving low-cost probabilistic 3D denoising with applications to Computed Tomography
Authors: Horenko Illia , Pospisil Lukas , Vecchi Edoardo , Albrecht Steffen , Gerber Alexander , Rehbock Beate , Stroh Albrecht , Gerber Susanne
Published: August 2021

We propose a pipeline for a synthetic generation of personalized Computer Tomography (CT) images, with a radiation exposure evaluation and a lifetime attributable risk (LAR) assessment. We perform a patient-specific performance evaluation for a broad range of denoising algorithms (including the most popular Deep Learning denoising approaches, wavelets-based methods, methods based on Mumford-Shah denoising etc.), focusing both on accessing the capability to reduce the patient-specific CT-induced LAR and on computational cost scalability. We introduce a parallel probabilistic Mumford-Shah denoising model (PMS), showing that it markedly-outperforms the compared common denoising methods in denoising quality and cost scaling. In particular, we show that it allows an approximately 22-fold robust patient-specific LAR reduction for infants and a 10-fold LAR reduction for adults. Using a normal laptop the proposed algorithm for PMS allows a cheap and robust (with the Multiscale Structural Similartity index > 90%) denoising of very large 2D videos and 3D images (with over 107voxels) that are subject to ultra-strong Gaussian and various non-Gaussian noises, also for Signal-to-Noise Ratios much below 1.0. The code is provided for open access.

One-sentence summary

Probabilisitc formulation of Mumford-Shah principle (PMS) allows a cheap quality-preserving denoising of ultra-noisy 3D images and 2D videos.
Vision-dependent specification of cell types and function in the developing cortex
Authors: Cheng Sarah , Butrus Salwan , Tan Liming , Xu Vincent , Sagireddy Srikant , Trachtenberg Joshua T. , Shekhar Karthik , Zipursky S. Lawrence
Published: August 2021

The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA-sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ∼200 genes, including regulators of cell adhesion and synapse formation. Vision-dependent regulation of one of these genes, encoding the inhibitory synaptic cell adhesion molecule IGSF9b, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell type-specific gene expression programs.
Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics
Authors: Tsai Kaitlyn , Stojković Vanja , Lee D. John , Young Iris D. , Szal Teresa , Vazquez-Laslop Nora , Mankin Alexander S. , Fraser James S. , Fujimori Danica Galonić
Published: August 2021

The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. In this study, we determined that the second-generation oxazolidinone radezolid also induces stalling with alanine at the penultimate position. However, the molecular basis for context-specificity of these inhibitors has not been elucidated. In this study, we determined high-resolution cryo-EM structures of both linezolid and radezolid-stalled ribosome complexes. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling by forcing the antibiotic to adopt a conformation that narrows the hydrophobic alanine pocket. Together, the structural and biochemical findings presented in this work provide molecular understanding of context-specific inhibition of translation by clinically important oxazolidinone antibiotics.
Bacterial growth, communication and guided chemotaxis in 3D bioprinted hydrogel environments
Authors: Müller Julia , Jäkel Anna C. , Richter Jonathan , Eder Markus , Falgenhauer Elisabeth , Simmel Friedrich C. , TU München F. C. Simmel
Published: August 2021

Bioprinting of engineered bacteria is of great interest for applications of synthetic biology in the context of living biomaterials, but so far only few viable approaches are available for the printing of gels hosting liveEscherichia colibacteria. Here we develop a gentle bioprinting method based on an alginate/agarose bioink that enables precise printing ofE.coliinto three-dimensional hydrogel structures up to 10 mm in height. Addition of a calcium peroxide-based oxygen generation system enables maturation of fluorescent proteins deep within the printed structures. We utilize spatial patterning with the bioprinter to control different types of chemical interaction between bacteria. We first show quorum sensing-based chemical communication between engineered sender and receiver bacteria placed at different positions inside the bioprint, and then demonstrate the fabrication of barrier structures defined by non-motile bacteria that can guide the movement of chemotactic bacteria inside a gel.
Asymmetric Redundancy of SoybeanNodule Inception(NIN) Genes in Root Nodule Symbiosis
Authors: Fu Mengdi , Sun Jiafeng , Li Xiaolin , Guan Yuefeng , Xie Fang
Published: August 2021

NINis one of the most important root nodule symbiotic genes as it is required for both infection and nodule organogenesis in legume. Unlike most legumes with a soleNINgene, there are four putativeNINgenes in soybean (Glycine max). Whether and how these orthologsNINgenes contribute to soybean-rhizobia symbiotic interaction remain unknown. In this study, we found that all fourGmNINgenes are induced by rhizobia, and that conserved CE and CYC binding motifs in their promoter regions are required for their expression in the nodule formation process. By generation of multiplexGmninmutants, we found thatGmnin1a nin2a nin2btriple mutant andGmnin1a nin1b nin2a nin2bquadruple mutant displayed similar defects in rhizobia infection and root nodule formation,Gmnin2a nin2bproduced less nodules but displayed hyper infection phenotype than wild type, while aGmnin1a nin1bdouble mutant nodulated as wild type. Overexpression ofGmNIN1a,GmNIN1b, GmNIN2a, andGmNIN2breduced nodule numbers after rhizobia inoculation, withGmNIN1boverexpression having the weakest effect. In addition, overexpression ofGmNIN1a,GmNIN2a, orGmNIN2b, but notGmNIN1b, produced malformed pseudo-nodule like structures without rhizobia inoculation. In conclusion, GmNIN1a, GmNIN2a and GmNIN2b play functionally redundant yet complicated roles for soybean nodulation. GmNIN1b, although is expressed at comparable level with other homologs, plays a minor role in root nodule symbiosis. Our work provides insight into the understanding of asymmetrically redundant function ofGmNINgenes in soybean.
Dopamine D3 Receptor Ligand Suppresses the Expression of Levodopa-Induced Dyskinesia in Nonhuman Primate Model of Parkinson’s Disease
Authors: Oh Thomas , Daadi Elyas S. , Kim Jeffrey , Daadi Etienne W. , Chen Peng-Jen , Roy-Choudhury Gourav , Bohmann Jonathan , Blass Benjamin E. , Daadi Marcel M.
Published: August 2021

Parkinson’s disease (PD) is a complex multisystem, chronic and so far incurable disease with significant unmet medical needs. The incidence of PD increases with aging and the expected burden will continue to escalate with our aging population. Since its discovery in the 1961 levodopa remains the gold standard pharmacotherapy for PD. However, the progressive nature of the neurodegenerative process in and beyond the nigrostriatal system causes a multitude of side effects, including levodopa-induced dyskinesia within 5 years of therapy. Attenuating dyskinesia has been a significant challenge in the clinical management of PD. We report on a small molecule that eliminates the expression of levodopa-induced dyskinesia and significantly improves PD-like symptoms. The lead compound PD13R we discovered is a dopamine D3 receptor partial agonist with high affinity and selectivity, orally active and with desirable drug-like properties. Future studies are aimed at developing this lead compound for treating PD patients with dyskinesia.
Pathological LSD1 mutations repress enhancer-mediated gene regulatory networks in early differentiation
Authors: Bunina Daria , Germain Pierre-Luc , Lopez Tobon Alejandro , Fernandez-Novel Marx Nadine , Arnold Christian , Ahern Andrew , Claringbould Annique , Lai Mang Ching , Rangasamy Sampath , Narayanan Vinodh , Lorentzen Peter , Park Karen M. , Adamo Antonio , Testa Giuseppe , Zaugg Judith , Noh Kyung-Min
Published: August 2021

Lysine-specific demethylase 1 (LSD1/KDM1A) demethylates both histone and non-histone substrates, recruits repressive chromatin complexes, and is increased in cancers. De novo LSD1 mutations impairing protein function lead to a rare developmental disorder, but the molecular details of the pathology remains unclear. Using patient-derived fibroblasts, reprogrammed pluripotent stem cells, and differentiated cells, we found over 4000 differentially expressed genes and 68 transcription factors (TFs) whose motif accessibilities changed upon LSD1 mutation. An enhancer-mediated gene regulatory network approach identified transcriptional repressors with impaired activity in fibroblast and stem cells, leading to erroneous activation of their target genes. We also revealed overall decreases in TF target gene expression during early lineage differentiation of LSD1 mutant stem cells, likely caused by increased activity of repressive histone deacetylases (HDACs), co-factors of LSD1. Indeed, an HDACs inhibitor restored changes in gene expression including downregulation phenotype. Our findings characterize the molecular pathogenesis of LSD1 mutations and suggest potential therapeutic strategies for the developmental disorder and cancers caused by LSD1 dysregulations.
Boruta-grid-search least square support vector machine for NO2 pollution prediction using big data analytics and IoT emission sensors
Authors: Balogun Habeeb , Alaka Hafiz , Egwim Christian Nnaemeka
Published: August 2021

Purpose

This paper seeks to assess the performance levels of BA-GS-LSSVM compared to popular standalone algorithms used to build NO2 prediction models. The purpose of this paper is to pre-process a relatively large data of NO2 from Internet of Thing (IoT) sensors with time-corresponding weather and traffic data and to use the data to develop NO2 prediction models using BA-GS-LSSVM and popular standalone algorithms to allow for a fair comparison.

Design/methodology/approach

This research installed and used data from 14 IoT emission sensors to develop machine learning predictive models for NO2 pollution concentration. The authors used big data analytics infrastructure to retrieve the large volume of data collected in tens of seconds for over 5 months. Weather data from the UK meteorology department and traffic data from the department for transport were collected and merged for the corresponding time and location where the pollution sensors exist.

Findings

The results show that the hybrid BA-GS-LSSVM outperforms all other standalone machine learning predictive Model for NO2 pollution.

Practical implications

This paper's hybrid model provides a basis for giving an informed decision on the NO2 pollutant avoidance system.

Originality/value

This research installed and used data from 14 IoT emission sensors to develop machine learning predictive models for NO2 pollution concentration.
Design and topological optimization of rear pressure bulkhead for a typical aircraft
Authors: Thakran Marshal , Meenakshi  , Sharma Jitender , Martin Charles Gilbert
Published: August 2021

Purpose

The purpose of this paper is to evaluate the model of a rear pressure bulkhead with different design optimizations to meet the pressurized cabin requirements of an aircraft.

Design/methodology/approach

This paper presents the results of the static analysis of a dome-shaped rear pressure bulkhead model designed in Catia-v5. Numerical analysis of model meshed in hyper-mesh and solved using Opti-Struct for iterative design optimizations.

Findings

All the iterative models are analyzed at 9 Psi. Rear pressure bulkhead designed with L-section stringer shows better results than the model optimized with T-section stringer for the same thickness. The model optimized with L-shaped stinger also reduces the weight of the bulkhead without affecting the structural integrity.

Practical implications

It has been concluded in this paper that the selection of specific shapes of the stringers shows a significant influence on weight reduction.

Originality/value

This paper provides a topical, technical insight into the design and development of a rear pressure bulkhead. It also outlines the future development of dome-shaped rear pressure bulkhead.
A modified model of conductor roughness for manufacturing copper lines of printedcircuit board
Authors: Wang Chong , Wang Yingjie , Adi Kegu , Huang Yunzhong , Chen Yuanming , Wang Shouxu , He Wei , Tang Yao , Sun Yukai , Zhang Weihua , Xu Chenggang , He Xuemei
Published: August 2021

Purpose

The purpose of this paper is to establish an accurate model to quantify the effect of conductor roughness on insertion loss (IL) and provide improved measurements and suggestions for manufacturing good conductive copper lines of printed circuit board.

Design/methodology/approach

To practically investigates the modified model of conductor roughness, three different kinds of alternate oxidation treatments were used to provide transmission lines with different roughness. The IL results were measured by a vector net analyzer for comparisons with the modified model results.

Findings

An accurate model, with only a 1.8% deviation on average from the measured values, is established. Compared with other models, the modified model is more reliable in industrial manufacturing.

Originality/value

This paper introduces the influence of tiny roughness structures on IL. Besides, this paper discusses the effect of current distribution on IL.
Digital transformation with enterprise architecture for smarter cities: a qualitative research approach
Authors: Anthony Jnr Bokolo , Abbas Petersen Sobah , Helfert Markus , Guo Hong
Published: August 2021

Purpose

Smart city services are supported by information and communication technologies (ICT) referred to as digital technologies which increasingly promise huge opportunities for growth but are faced with system alignment and data integration issues when providing digital services. Therefore, this study aims to use enterprise architecture (EA) in digital transformation of cities by developing an architecture to address system alignment and data integration in digital transformation of cities.

Design/methodology/approach

Qualitative method is applied to evaluate the presented architecture based on electric-mobility (e-mobility) scenario, and data was collected using case study via interviews from a municipality in Norway to validate the applicability of EA for digital transformation of city services.

Findings

Findings from the interviews were represented in ArchiMate language to model the digital transformation of e-mobility in smart cities. Findings suggest that the architecture serves as a guide to recommend urban administrators of the potential of EA and digital transformation in addressing system alignment and data integration issues in smart cities.

Research limitations/implications

Data used in this study is from a single case, hence there is a need to evaluate the application of EA for digital transformation of city services with data collected from multi-cases.

Practical implications

This study adopts enterprise architecture approach to support city transformation as it has been widely applied by institutions to align business and ICT components.

Social implications

This study provides implication on how municipalities can use EA and digital transformations towards a sustainable smart city.

Originality/value

An architecture is presented that can be used as a guide to help urban developers and designers in deploying sustainable transport policies for smart cities. Additionally, EA is used to foster digitalization towards achieving system alignment and data integration in cities to support urban environment as they digitally transform services provided to citizens.
A temporal study on subordinate’s response to destructive leadership: voice withdrawal as a conflict coping mechanism
Authors: Pandey Agrata , Nambudiri Ranjeet , Selvaraj Patturaja , Sadh Ashish
Published: August 2021

Purpose

The literature on destructive leadership has largely ignored the perspective of the subordinate, especially in terms of conflict coping mechanisms. This study aims to integrate research on destructive leadership and subordinates’ voice behaviour as a conflict coping mechanism. Drawing on the social exchange, conservation of resources and social identity theories, it argues that destructive leadership negatively affects employees’ voice behaviour and that this relationship is moderated by subordinate personality and organization climate.

Design/methodology/approach

The proposed model was tested on a sample of 275 professionals working in the banking and insurance sector in India using a temporal research design with data collected in two phases six months apart. Partial least squares structural equation modelling was used for data analysis.

Findings

The results support the main effect relationship between destructive leadership and subordinates’ voice behaviour and the moderation of subordinates’ personality and organizational climate. Temporal analysis indicates that the nature of some relationships changed across the two time periods.

Practical implications

A greater understanding of destructive leader behaviour and resultant coping strategies of subordinates is likely to provide insights for managers facing such situations. The findings of this study will inform the creation of redressal and voice mechanisms in organizations.

Originality/value

This is among the first studies to examine the impact of negative forms of leadership on subordinates’ conflict coping mechanisms using a temporal lag design across two time periods.
Airbnb and hotels during COVID-19: different strategies to survive
Authors: Gyódi Kristóf
Published: August 2021

Purpose

The purpose of this paper is to examine the impact of the COVID-19 pandemic on the traditional hotel industry and Airbnb in nine major European cities. The author examines differences between the two business models and analyses various strategies of Airbnb hosts to cope with the crisis.

Design/methodology/approach

A detailed empirical analysis is presented based on data from STR and Inside Airbnb for the period January 2018–September 2020. To assess the impact of the pandemic on the hotel industry, year-to-year changes in various performance metrics are presented. The author also investigates the impact of the pandemic on Airbnb prices with panel data regression analysis. Using text-mining methods, signs for new use-cases are explored, including renting flats for home-office or quarantine.

Findings

The results support that Airbnb supply is more flexible. While hotel supply quickly returned to a level close to 2019, the average number of Airbnb listings was lower by more than 15%. Furthermore, the price analysis showed that Airbnb rates decreased more moderately than hotel prices. These findings suggest that a significant share of hosts pivoted from short-term accommodation provision and used their property differently, e.g. rented on a long-term basis. The analysis of listing characteristics revealed that the role of longer stays increased; however, the results do not support a shift towards advertising listings for home-office or quarantine purposes.

Originality/value

This paper presents the impact of the pandemic on the hospitality sector in a wide sample of European cities, explores the adjustment of hotels and Airbnb and provides new evidence on the differences between the business models.
Performance management of OECD countries on Covid-19 pandemic: a criticism using data envelopment analysis models
Authors: Doğan Mustafa İsa , Özsoy Volkan Soner , Örkcü H. Hasan
Published: August 2021

Purpose

The Covid-19 pandemic spread rapidly around the world and required strict restriction plans and policies. In most countries around the world, the outbreak of the disease has been serious and has greatly affected the health system and the economy. The factors such as the number of patients with chronic diseases, the number of people over 65 years old, hospital facilities, the number of confirmed Covid-19 cases, the recovering Covid-19 cases and the number of deaths affect the rate of spread of Covid-19. This study aims to evaluate the performances of 21 Organisation for Economic Co-operation and Development (OECD) countries against the Covid-19 outbreak using three data envelopment analysis (DEA) models.

Design/methodology/approach

In this study, the performance of 21 OECD countries to manage the Covid-19 process has been analysed weekly via DEA which is widely used in various practical problems and provides a general framework for efficiency evaluation problems using the inputs and outputs of decision-making units.

Findings

The analysis showed that 11 countries out of 21 countries were efficient for selected weeks. According to the DEA results from the 20-week review (09 April 2020–20 August 2020), information about the course of the epidemic prevention and the normalization process for any country can be obtained.

Originality/value

In this study, due to the problem of the discrimination power of DEA, the cross-efficiency model and the super-efficiency model also used. In addition, the output-oriented model was preferred in this study for Covid-19 management efficiency.
Nascent entrepreneur characteristic predictors of early-stage entrepreneurship outcomes
Authors: Lanivich Stephen E. , Lyons Laci M. , Wheeler Anthony R.
Published: August 2021

Purpose

Social cognitive theory suggests that entrepreneurs' characteristics affect entrepreneurial outcomes through interaction with their environment. This study examines the relationship between entrepreneurs' characteristics and performance in the context of entrepreneurial nascence.

Design/methodology/approach

This study investigated lagged-panel responses from a sample of 100 confirmed nascent entrepreneurs. Data collected on three separate occasions included core self-evaluations, commitment, fear of failure and success. PLS analysis was used to assess mediation of commitment on the self-evaluation – success relationship.

Findings

Core self-evaluations are an important predictor of entrepreneurial success in nascent-stage entrepreneurs participating in pre-venture assistance programs; positively affecting success and commitment, while negatively affecting fear of failure.

Research limitations/implications

This investigation contributes to a fuller understanding of social cognitive theory as it pertains to nascent entrepreneurship. Furthermore, contrary to general expectations found in the entrepreneurship literature, the authors uncover a context where entrepreneurs' characteristics are relevant predictors of early entrepreneurial outcomes.

Practical implications

Results showed core self-evaluations as a robust predictor of perceived success in nascent entrepreneurs. Administrators of pre-venture assistance programs should consider screening applicants to programs designed to assist nascent entrepreneurial opportunity development for signs of high core self-evaluations.

Originality/value

This study advances theory by (1) demonstrating the value of assessing nascent entrepreneurs' core self-evaluations as a specific predictor of early-stage entrepreneurial outcomes, (2) suggesting social interaction amidst participation in pre-venture assistance programs makes commitment a salient part of perceived success and (3) providing evidence that entrepreneur-level characteristics need consideration in the context of nascent entrepreneurship and pre-venture assistance programs.
Perspective of volunteer staff on the effectiveness of peer-support programs: a case study
Authors: Dudley-Miller Vanessa , Radel Jeff
Published: August 2021

Purpose

This study aims to explore perceived effectiveness in the Warriors' Ascent program through interviews of volunteer staff, to leverage improvements in the design and delivery of programs through peer-volunteers.

Design/methodology/approach

Focused interviews were conducted to explore peer-volunteer perspectives on program effectiveness. The alignment of themes and statements emerging from interviews was explored in detail relative to the program curriculum.

Findings

Five main themes emerged, with alignment for 86% of the peer-volunteers’ commentary and program curriculum. Areas of non-alignment may present opportunities for program growth.

Practical implications

Analysis of peer-volunteer perspectives on practical activities and overall program effectiveness identified options to enhance program delivery. Warriors’ Ascent and both existing and emerging organizations (such as those who will serve distressed frontline pandemic workers) are essential social resources poised to evolve by encompassing appreciation and more effective use of non-professional volunteer support staff.

Originality/value

Peer-volunteers supporting behavior change programs are an emerging focus for research. Peer-volunteers contribute unique perspectives, common experiences and building of relations with a program’s participants serving as an effective agent of change contributing toward healthier lifestyles. Considering the influences of peer-volunteers during program evaluation allows triangulation among sources of information and offers additional opportunities for influencing program growth.