bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher-order olfactory neurons in the lateral horn supports odor valence and odor identity coding in Drosophila
Authors: Chakraborty Sudeshna Das , Chang Hetan , Hansson Bill S. , Sachse Silke 
Published: October 2021

AbstractUnderstanding neuronal representations of odor-evoked activities and their progressive transformation from the sensory level to higher brain centers features one of the major aims in olfactory neuroscience. Here, we investigated how odor information is transformed and represented in higher-order neurons of the lateral horn, one of the higher olfactory centers implicated in determining innate behavior, using Drosophila melanogaster. We focused on a subset of third-order glutamatergic lateral horn neurons (LHNs) and characterized their odor coding properties in relation to their presynaptic partner neurons, the projection neurons (PNs) by two-photon functional imaging. We found that odors evoke reproducible, stereotypic and odor-specific response patterns in LHNs. Notably, odor-evoked responses in these neurons are valence-specific in a way that their response amplitude is positively correlated with innate odor preferences. We postulate that this valence-specific activity is the result of integrating inputs from multiple olfactory channels through second-order neurons. GRASP and micro-lesioning experiments provide evidence that glutamatergic LHNs obtain their major excitatory input from uniglomerular PNs, while they receive an odor-specific inhibition through inhibitory multiglomerular PNs. In summary, our study indicates that odor representations in glutamatergic LHNs encode hedonic valence and odor identity and primarily retain the odor coding properties of second-order neurons.
Integrative genomics uncover mechanisms of renal medullary carcinoma transformation, microenvironment landscape and therapeutic vulnerabilities
Authors: Vokshi Bujamin H. , Davidson Guillaume , Helleux Alexandra , Rippinger Marc , Haller Alexandre R. , Gantzer Justine , Thouvenin Jonathan , Baltzinger Philippe , Bouarich Rachida , Manriquez Valeria , Zaidi Sakina , Msaouel Pavlos , Su Xiaoping , Lang Hervé , Tricard Thibault , Lindner Véronique , Surdez Didier , Kurtz Jean-Emmanuel , Bourdeaut Franck , Tannir Nizar M. , Davidson Irwin , Malouf Gabriel G. 
Published: October 2021

AbstractRenal medullary carcinoma (RMC) is an aggressive desmoplastic tumour driven by bi-allelic loss of SMARCB1, however the cell-of-origin, the oncogenic mechanism and the features of its microenvironment remain poorly understood. Using single-cell and multi-region sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into at least three RMC cell states along an epithelial-mesenchymal gradient through a transcriptional switch involving loss of renal transcription factor TFCP2L1 and gain of a NFE2L2-associated ferroptosis resistance program. SMARCB1 re-expression in cultured RMC cells reactivates TFCP2L1 that relocates SWI/SNF from the promoters of the MYC-driven oncogenic program to the enhancers of TAL identity genes followed by ferroptotic cell death. We further show that RMC is associated with abundant M2-type macrophages and cancer-associated fibroblasts (CAFs) and we identify key regulatory cross-talks that shape this immunosuppressive microenvironment. Together our data describe the molecular events of RMC transformation and identify novel therapeutically targetable vulnerabilities.
Hemodynamic Correlates of Fluctuations in Neuronal Excitability: A Simultaneous Paired Associative Stimulation (PAS) and functional Near Infra-Red Spectroscopy (fNIRS) Study
Authors: Cai Zhengchen , Pellegrino Giovanni , Spilkin Amanda , Delaire Edouard , Uji Makoto , Abdallah Chifaou , Lina Jean-Marc , Fecteau Shirley , Grova Christophe 
Published: October 2021

AbstractBackgroundThe relationship between task-related hemodynamic activity and brain excitability is poorly understood in humans as it is technically challenging to combine simultaneously non-invasive brain stimulation and neuroimaging modalities. Cortical excitability corresponds to the readiness to become active and as such it may be linked to metabolic demand.HypothesesCortical excitability and hemodynamic activity are positively linked so that increases in hemodynamic activity correspond to increases in excitability and vice-versa.MethodsFluctuations of excitability and hemodynamic activity were investigated via simultaneous Transcranial Magnetic Stimulation (TMS) and functional Near Infrared Spectroscopy (fNIRS). Sixteen healthy subjects participated in a sham-controlled, pseudorandomized, counterbalanced study with PAS (PAS10/PAS25/Sham) on the right primary motor cortex (M1). The relationship between M1 excitability (Motor Evoked Potentials, MEP) and hemodynamic responses to finger tapping reconstructed via personalized fNIRS was assessed.ResultsHemodynamic activity exhibited a significant correlation with cortical excitability: increased HbO and HbR (absolute amplitude) corresponded to increased excitability and vice-versa (r=0.25; p=0.03 and r=0.16; p=0.17, respectively). The effect of PAS on excitability and hemodynamic activity showed a trend of positive correlation: correlation of MEP ratios (post-PAS/pre-PAS) with HbO and HbR ratios (r=0.19, p=0.29; r=0.18, p=0.30, respectively).ConclusionsTMS-fNIRS is a suitable technique for simultaneous investigation of excitability and hemodynamic responses and indicates a relationship between these two cortical properties. PAS effect is not limited to cortical excitability but also impacts hemodynamic processes. These findings have an impact on the application of neuromodulatory interventions in patients with neuropsychiatric disorders.
Assessing the Functionality of RNA Interference (RNAi) in the Phloem-feeding Maize pestDalbulus maidis
Authors: Jones Tara-Kay L. , Bernal Julio S. , Medina Raul F. 
Published: October 2021

AbstractDalbulus maidis[(DeLong & Wolcott), corn leafhopper], a phloem-feeding insect, is the most efficient vector of maize stunting pathogens (Spiroplasma kunkelii, Maize bushy stunt phytoplasma, and Maize rayado fino virus) in the Americas. Studies involving gene editing in insects are rapidly providing information that can potentially be used for insect vector and plant disease control. RNA interference (RNAi), a sequence-specific gene silencing method, is one of the most widely used molecular tools in functional genomics studies. RNAi uses exogenous double-stranded RNA (dsRNA) or small interfering RNA (siRNA) to prevent the production of proteins by inhibiting the expression of their corresponding messenger RNA (mRNA). In this study, we measured the efficacy of gene silencing, and its effects onD. maidismortality as proof of concept that RNAi is a viable tool for use in genetic pest control of phloem-feeding insects. Oral delivery of dsRNA using an artificial diet was used to silence two key insect genes, vacuolar ATP synthase subunit B, and subunit D (V-ATPase BandV-ATPase D). Our results showed reduced gene expression ofV-ATPase BandV-ATPase Dafter ingestion of dsRNA, and significantly higher mortality, and wing deformation, associated with reduced gene expression, compared to control insects that were not orally fed dsRNA. These results reveal RNAi as a viable tool for use in genetic pest control of phloem-feeding insects, and a way for further functional genomic studies, such as identification of potential target genes for either population suppression or population replacement of this vector of maize diseases.
Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers
Authors: Belyy Vladislav , Zuazo-Gaztelu Iratxe , Alamban Andrew , Ashkenazi Avi , Walter Peter 
Published: October 2021

AbstractProtein folding homeostasis in the endoplasmic reticulum (ER) is regulated by a signaling network, termed the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) is an ER membrane-resident kinase/RNase that mediates signal transmission in the most evolutionarily conserved branch of the UPR. Dimerization and/or higher-order oligomerization of IRE1 are thought to be important for its activation mechanism, yet the actual oligomeric states of inactive, active, and attenuated mammalian IRE1 complexes remained unknown. We developed an automated two-color single-molecule tracking approach to dissect the oligomerization of tagged endogenous human IRE1 in live cells. In contrast to previous models, our data indicate that IRE1 exists as a constitutive homodimer at baseline and assembles into small oligomers upon ER stress. We demonstrate that the formation of inactive dimers and stress-dependent oligomers is fully governed by IRE1’s lumenal domain. Phosphorylation of IRE1’s kinase domain occurs more slowly than oligomerization and is retained after oligomers disassemble back into dimers. Our findings suggest that assembly of IRE1 dimers into larger oligomers specifically enables trans- autophosphorylation, which in turn drives IRE1’s RNase activity.
Bile Acid Regulates the Colonization and Dissemination ofCandida albicansfrom the Gastrointestinal Tract by Controlling Host Defense System and Microbiota
Authors: Thangamani Shankar , Monasky Ross , Lee Jung Keun , Antharam Vijay , HogenEsch Harm , Hazbun Tony , Jin Yan , Gu Haiwei , Guo Grace L. 
Published: October 2021

AbstractCandida albicans(CA), a commensal and opportunistic eukaryotic organism, frequently inhabits the gastrointestinal (GI) tract and causes life-threatening infections. Antibiotic-induced gut dysbiosis is a major risk factor for increased CA colonization and dissemination from the GI tract. We identified a significant increase of taurocholic acid(TCA),a major bile acid in antibiotic-treated mice susceptible to CA infection.In vivofindings indicate that administration of TCA through drinking water is sufficient to induce colonization and dissemination of CA in wild type and immunosuppressed mice. Treatment with TCA significantly reduced mRNA expression of immune genesang4andCxcr3in the colon. In addition, TCA significantly decreased the relative abundance of three culturable species of commensal bacteria,Turicibacter sanguinis, Lactobacillus johnsonii, andClostridium celatum, in both cecal contents and mucosal scrapings from colon. Taken together, our results indicate that TCA promotes fungal colonization and dissemination of CA from the GI tract by controlling host defense system and intestinal microbiota that play a critical role in regulating CA in the intestine.ImportanceBroad-spectrum antibiotics, FDA-approved bile acid drugs, and probiotics used to control metabolic and infectious diseases profoundly alter the level of TCA in the gut. Furthermore, TCA level is highly altered in a subset of cancer, colitis and surgery patients who are highly susceptible to CA infection. Inadvertently, these therapies and disease conditions could be either promoting CA colonization and dissemination. Our findings indicate that TCA alone can induce fungal colonization and dissemination from the intestine. Results from this study will have a significant impact in understanding how bile acids interact with the microbiota and host in regulating invasive fungal infections that originate from the intestine and to develop potential new antifungal therapeutics.
Pyronaridine Protects Against SARS-CoV-2 in Mouse
Authors: Puhl Ana C. , Gomes Giovanni F. , Damasceno Samara , Godoy Andre S. , Noske Gabriela D. , Nakamura Aline M. , Gawriljuk Victor O. , Fernandes Rafaela S. , Monakhova Natalia , Riabova Olga , Lane Thomas R. , Makarov Vadim , Veras Flavio P. , Batah Sabrina S. , Fabro Alexandre T. , Oliva Glaucius , Cunha Fernando Q. , Alves-Filho José C. , Cunha Thiago M. , Ekins Sean 
Published: October 2021

AbstractThere are currently relatively few small-molecule antiviral drugs that are either approved or emergency approved for use against SARS-CoV-2. One of these is remdesivir, which was originally repurposed from its use against Ebola and functions by causing early RNA chain termination. We used this as justification to evaluate three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg. Out of these we previously identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. Herein, the in vivo efficacy of pyronaridine has now been assessed in a K18-hACE transgenic mouse model of COVID-19. Pyronaridine treatment demonstrated a statistically significant reduction of viral load in the lungs of SARS CoV-2 infected mice. Furthermore, the pyronaridine treated group reduced lung pathology, which was also associated with significant reduction in the levels of pro-inflammatory cytokines/chemokine and cell infiltration. Notably, pyronaridine inhibited the viral PLpro activity in vitro (IC50 of 1.8 µM) without any effect on Mpro, indicating a possible molecular mechanism involved in its ability to inhibit SARS-CoV-2 replication. Interestingly, pyronaridine also selectively inhibits the host kinase CAMK1 (IC50 of 2.4 µM). We have also generated several pyronaridine analogs to assist in understanding the structure activity relationship for PLpro inhibition. Our results indicate that pyronaridine is a potential therapeutic candidate for COVID-19.One sentence summaryThere is currently intense interest in discovering small molecules with direct antiviral activity against the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Pyronaridine, an antiviral drug with in vitro activity against Ebola, Marburg and SARS-CoV-2 has now statistically significantly reduced the viral load in mice along with IL-6, TNF-α, and IFN-β ultimately demonstrating a protective effect against lung damage by infection to provide a new potential treatment for testing clinically.
Structural mapping of antibody landscapes to human betacoronavirus spike proteins
Authors: Bangaru Sandhya , Antanasijevic Aleksandar , Kose Nurgun , Sewall Leigh M. , Jackson Abigail M. , Suryadevara Naveenchandra , Zhan Xiaoyan , Torres Jonathan L. , Copps Jeffrey , Torrents de la Peña Alba , Crowe James E. , Ward Andrew B. 
Published: October 2021

AbstractPreexisting immunity against seasonal coronaviruses (CoV) represents an important variable in predicting antibody responses and disease severity to Severe Acute Respiratory Syndrome CoV-2 (SARS-2) infections. We used electron microscopy based polyclonal epitope mapping (EMPEM) to characterize the antibody specificities against β-CoV spike proteins in sera from healthy donors (HDs) or SARS-2 convalescent donors (CDs). We observed that most HDs possessed antibodies specific to seasonal human CoVs (HCoVs) OC43 and HKU1 spike proteins while the CDs showed reactivity across all human β-CoVs. Detailed molecular mapping of spike-antibody complexes revealed epitopes that were differentially targeted by antibodies in preexisting and convalescent serum. Our studies provide an antigenic landscape to β-HCoV spikes in the general population serving as a basis for cross-reactive epitope analyses in SARS-2 -infected individuals.One-Sentence summaryWe present the epitope mapping of polyclonal antibodies against beta-coronavirus spike proteins in human sera.
Biodegradation of naphthalene mediated by the plant growth promoting rhizobacteria
Authors: Timmusk Salme , Teder Tiiu , Behers Lawrence 
Published: October 2021

AbstractWe compared the ability of two bacterial strains, Paenibacillus polymyxa A26 and P. polymyxa A26Sfp, for biodegradation of naphthalene (NAP). The studies were performed under simulated laboratory conditions, in liquid medium and soil with different carbon sources, pH and salt contents. Changes in the luminescence inhibition of Aliivibrio fischeri, as an indicator of the baseline toxicity, were observed in degradation mixtures during 7 days of incubation. While both strains expressed the best growth and NAP degradation ability in the minimal salt medium containing sucrose and 5% NaCl at pH 8, the mutant strain remained effective even under extreme conditions.A26Sfp was found to be an efficient and potentially industrially important polycyclic aromatic hydrocarbon degradation strain. Its extracellular polysaccharide production is 30% and glucan production twice that of the wild type A 26. The surface tension reduction ability was ascertained as 25–30% increased emulsification ability.
Cytoskeletal regulation of a transcription factor by DNA mimicry
Authors: Haque Farah , Freniere Christian , Ye Qiong , Mani Nandini , Wilson-Kubalek Elizabeth M. , Ku Pei-I , Milligan Ronald A. , Subramanian Radhika 
Published: October 2021

AbstractA long-established strategy for transcription regulation is the tethering of transcription factors to cellular membranes. In contrast, the principal effectors of Hedgehog signaling, the Gli transcription factors, are regulated by microtubules in the primary cilium and the cytoplasm. How Gli is tethered to microtubules remains unclear. We uncover DNA mimicry by the ciliary kinesin Kif7 as a mechanism for the recruitment of Gli to microtubules, revealing a new mode of tethering a DNA-binding protein to the cytoskeleton. Gli increases the Kif7-microtubule affinity and consequently modulates the localization of both proteins to microtubules and the cilium tip. Thus, the kinesin-microtubule system is not a passive Gli tether but a regulatable platform tuned by the kinesin-transcription factor interaction. We re-tooled the unique DNA-mimicry-based Gli-Kif7 interaction for inhibiting the nuclear and cilium localization of Gli. This strategy can be potentially exploited for downregulating erroneously activated Gli in human cancers.
Computation of erosion in a hydro turbine
Authors: Ghenaiet Adel 
Published: October 2021

PurposeThis study aims to investigate the trajectories of sand particles and erosion wear in a hydraulic turbine model.Design/methodology/approachThe Lagrangian-based approach is used to track large numbers of sand particles and determine their impact through the hydro turbine components. The tracking procedure includes the stochastic eddy interaction model and the squeeze film effect. The number of particles, sizes and release positions are conformed to the particle concentration and size distribution. The impact locations, frequency and conditions of impacts are used to estimate the erosion rates and thereby the eroded mass from the distributor vane and the rotor blade and their deteriorated geometry.FindingsThe patterns of erosion in the stationary and rotating parts differ significantly and the effect of the initial position of the runner blade is elucidated. The distributor vane is characterized by a widespread of erosion over the pressure side. Typically, the surface beyond the throat and the root and tip junctions are the regions prone to erosion wear. The entry region of the runner blade is subject to a high number of impacts resulting in high erosion rates visible from the forepart of the blade pressure side.Practical implicationsThe erosion patterns and geometry deterioration may serve to evaluate the drop in the hydraulic performance and to select the appropriate surface coating to extend the lifetime of the turbomachinery parts and reduce the maintenance cost.Originality/valueErosion developments reveal a strong dependence on the blade position against the distributor vane and the particle size and concentration level.
The promises and the reality of smart, digital telecare in England
Authors: Stirling Phoebe , Burgess Gemma 
Published: October 2021

Purpose
This paper asks how the introduction of “smart” digital technologies might affect the goals that can be attributed to telecare for older people, by those coordinating its provision.

Design/methodology/approach
A total of 29 in-depth, qualitative interviews were conducted with local authorities, housing associations and other organisations coordinating smart telecare provision, as well as telecare manufacturers and suppliers. Interviews were analysed by using qualitative thematic analysis.

Findings
The analysis reveals discrepancies between the goals and outcomes of smart telecare provision, according to those coordinating service delivery. This study concludes that the goal for smart telecare to be preventative and cost-efficient may be complicated by various organisational and operational challenges associated with coordinating provision.

Originality/value
New, “smart” telecare technology for older people stands apart from earlier, user-activated or automatic devices. It may have distinct and under-researched organisational and ethical implications.
Modeling and analysis of barriers in controlling TB: developing countries' perspective
Authors: Mittal Palka , Ajmera Puneeta , Jain Vineet , Aggarwal Gaurav 
Published: October 2021

PurposeTuberculosis (TB) continues to c-exist with humans despite many TB control programs and elimination strategies. This depicts that some barriers are not allowing achieving the desired results. The current study aims to focus on identification and ranking of such barriers to facilitate TB control programs in developing countries.Design/methodology/approachIn the present study, 13 barriers that can influence success rate of TB elimination strategies have been recognized with an in-depth assessment of related literature and opinions of specialists from medical industry and academic world. The interpretive structural modeling (ISM) and decision-making trial and evaluation laboratory (DEMATEL) techniques have been employed for the ranking of barriers.FindingsBased on driving power of barriers, the study coined that underinvestment is a major barrier followed by poor implementation of government policies and programs, poverty and poor primary health care infrastructure.Research limitations/implicationsThe findings may guide healthcare service providers and researchers in analyzing the barriers and understanding the necessity of further advancements to decrease the count of already existing and incident cases.Practical implicationsPolicy- and decision-makers may utilize the information on dependence and driving power of barriers for better planning and effective execution of TB control strategies.Originality/valueAlthough a lot of literature is available on different barriers that are affecting success of TB strategies, the current study analyzes all the key barriers collectively for the prioritization of barriers.