bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial and quorum sensing inhibitory activity of Bacillus safensis EPB9 isolated from the red alga Halymenia durvillei
Authors: Padayao Mary Hannah Rose , Padayao Francis Reuben Paul , Patalinghug Jenny Marie , Raña Gem Stephen , Yee Jonie , Geraldino Paul John , Quilantang Norman
Published: January 2023

Seaweed-associated bacteria participate in complex interactions necessary for the health and defense of their host. It involves the production of antifouling metabolites and antimicrobials to prevent secondary colonization of pathogenic epibiota. Halymenia durvillei, commonly known as “red sea lettuce,” is a red alga ubiquitously distributed in the Indo-Pacific region. It is cultivated in the Philippines due to its abundance in high-value pigments such as phycoerythrin and r-phycocyanin. However, there are no studies regarding the microbial community associated with H. durvillei and its potential applications. This study aimed to isolate and identify the epiphytic bacteria of H. durvillei and determine their antimicrobial and quorum-sensing inhibitory (QSI) effects. The thalli of H. durvillei were collected at the shores of Santa Fe, Bantayan, Cebu, Philippines. The bacterial isolates were identified using 16S rRNA, and their ethyl acetate (EtOAc) extracts were subjected to antimicrobial susceptibility tests against representative species of yeast, gram-negative, and gram-positive bacteria. Their QSI activity against Chromobacterium violaceum was also determined. Fourteen distinct bacterial colonies belonging to four genera, namely, Alteromonas (3), Bacillus (5), Oceanobacillus (1), and Vibrio (5) were successfully isolated and identified. All fourteen bacterial isolates exhibited antibiotic effects against gram-negative and gram-positive bacteria. In particular, EPB9, identified as B. safensis, showed consistently strong potent inhibition against Escherichia coli, Staphylococcus aureus, and S. epidermidis having minimum inhibitory concentrations (MIC) ranging from 0.0625 – 1.0 mg mL-1. In contrast, all fourteen isolates showed weak antifungal effects. Both B. safensis (EPB 9) and B. australimaris (EPB15) exhibited QSI effects at 100 mg mL-1 showing opaque zones of 3.1 ± 0.9 mm and 3.8 ± 0.4 mm, respectively. This study is the first to isolate and identify the distinct microbial epiphytic bacterial community in H. durvillei and show that they can be used as an abundant resource for new antibiotics and QSI bioactive.
Collection and curation of prokaryotic genome assemblies from type strains at NCBI
Authors: Kannan Sivakumar , Sharma Shobha , Ciufo Stacy , Clark Karen , Turner Seán , Kitts Paul A. , Schoch Conrad L. , DiCuccio Michael , Kimchi Avi
Published: January 2023

The public sequence databases are entrusted with the dual responsibility of providing an accessible archive to all submitters and supporting data reliability and its re-use to all users. Genomes from type materials can act as an unambiguous reference for a taxonomic name and play an important role in comparative genomics, especially for taxon verification or reclassification. The National Center for Biotechnology Information (NCBI) collects and curates information on prokaryotic type strains and genomes from type strains. The average nucleotide identity (ANI)-based quality control processes introduced at NCBI to verify the genomes from type strains and improve related sequence records are detailed here. Using the curated genomes from type strains as reference, the taxonomy of over 1.1 million GenBank genomes were verified and the taxonomy of over 7000 new submissions before acceptance to GenBank and over 1800 existing genomes in GenBank were reclassified.
HAVOC: Small-scale histomic mapping of biodiversity across entire tumor specimens using deep neural networks
Authors: Dent Anglin , Faust Kevin , Lam K. H. Brian , Alhangari Narges , Leon Alberto J. , Tsang Queenie , Kamil Zaid Saeed , Gao Andrew , Pal Prodipto , Lheureux Stephanie , Oza Amit , Diamandis Phedias
Published: January 2023

Intra-tumoral heterogeneity can wreak havoc on current precision medicine strategies due to challenges in sufficient sampling of geographically separated areas of biodiversity distributed across centimeter-scale tumor distances. In particular, modern tissue profiling approaches are still largely designed to only interrogate small tumor fragments; which may constitute a minute and non-representative fraction of the overall neoplasm. To address this gap, we developed a pipeline that leverages deep learning to define topographic histomorphologic fingerprints of tissue and create Histomic Atlases of Variation Of Cancers (HAVOC). Importantly, using a number of spatially-resolved readouts, including mass-spectrometry-based proteomics and immunohistochemisy, we demonstrate that these personalized atlases of histomic variation can define regional cancer boundaries with distinct biological programs. Using larger tumor specimens, we show that HAVOC can map spatial organization of cancer biodiversity spanning tissue coordinates separated by multiple centimeters. By applying this tool to guide profiling of 19 distinct geographic partitions from 6 high-grade gliomas, HAVOC revealed that distinct states of differentiation can often co-exist and be regionally distributed across individual tumors. Finally, to highlight generalizability, we further benchmark HAVOC on additional tumor types and experimental models of heterogeneity. Together, we establish HAVOC as a versatile and accessible tool to generate small-scale maps of tissue heterogeneity and guide regional deployment of molecular resources to relevant and biodiverse tumor niches.
NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression
Authors: Sim Nicholas , Yinghui Li
Published: January 2023

Gliomas are among the most invasive and chemo-resistant cancers, making them challenging to treat. Chronic inflammation is one of the key drivers of glioma progression as it promotes the aberrant activation of inflammatory pathways such as NF-κB signalling which drives cancer cell invasion, angiogenesis and tissue remodelling. NF-κB factors typically dimerize with its own family members, but emerging evidence of their promiscuous interactions with other oncogenic factors have been reported to activate the transcription of new target genes and function. Here, we show that non-canonical NF-κB activation directly regulates p52 at theETS1promoter to activate its expression. This in turn impacts the genomic and transcriptional landscape of ETS1 in a glioma-specific manner. We further show that enhanced non-canonical NF-κB signalling promotes the co-localization of p52 and ETS1, resulting in the transcriptional activation of non-κB and/or non-ETS glioma-promoting genes. We conclude that p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression.
Differential effects of PTH (1-34), PTHrP (1-36) and abaloparatide on the murine osteoblast transcriptome
Authors: Mosca Michael J , He Zhiming , Ricarte Florante R. , Le Henaff Carole , Partridge Nicola C.
Published: January 2023

Teriparatide (PTH(1-34)) and its analogs, PTHrP(1-36) and abaloparatide (ABL) have been used for the treatment of osteoporosis, but their efficacy over long-term use is significantly limited. The 3 peptides exert time- and dose-dependent differential responses in osteoblasts, leading us to hypothesize that they may also differentially modulate the osteoblast transcriptome. We show that treatment of mouse calvarial osteoblasts with 1 nM of the 3 peptides for 4 h results in RNA-Seq data with PTH(1-34) regulating 367 genes, including 194 unique genes; PTHrP(1-36) regulating 117 genes, including 15 unique genes; and ABL regulating 179 genes, including 20 unique genes. There were 83 genes shared among all 3 peptides. Gene ontology analyses showed differences in Wnt signaling, cAMP-mediated signaling, bone mineralization, morphogenesis of a branching structure in biological processes; receptor ligand activity, transcription factor activity, cytokine receptor/binding activity and many other actions in molecular functions. The 3 peptides increasedVdr, Cited1andPde10amRNAs in a pattern similar toRankl, i.e., PTH(1-34) > ABL > PTHrP(1-36). mRNA abundance of other genes based on gene/pathway analyses, includingWnt4, Wnt7, Wnt11, Sfrp4, Dkk1, Kcnk10, Hdac4, Epha3, Tcf7, Crem, Fzd5, Pp2r2a, andDvl3showed that some genes were regulated similarly by all 3 peptides; others were not. Finally, siRNA knockdowns of SIK1/2/3 and CRTC1/2/3 in PTH(1-34)-treated cells revealed thatVdrandWnt4genes are regulated by SIKs and CRTCs, while others are not. Although many studies have examined PTH signaling in the osteoblast/osteocyte, ours is the first to examine the global effects of these peptides on the osteoblast transcriptome. Further delineation of which signaling events are attributable to PTH(1-34), PTHrP(1-36) or ABL exclusively and which are shared among all 3 will help improve our understanding of the effects these peptides have on the osteoblast and lead to the refinement of PTH-derived treatments for osteoporosis.
Top-down control of exogenous attentional selection is mediated by beta coherence in prefrontal cortex
Authors: Dubey Agrita , Markowitz David A. , Pesaran Bijan
Published: January 2023

Salience-driven exogenous and goal-driven endogenous attentional selection are two distinct forms of attention that guide selection of task-irrelevant and task-relevant targets in primates. During conflict i.e, when salience and goal each favor the selection of different targets, endogenous selection of the task-relevant target relies on top-down control. Top-down attentional control mechanisms enable selection of the task-relevant target by limiting the influence of sensory information. Although the lateral prefrontal cortex (LPFC) is known to mediate top-down control, the neuronal mechanisms of top-down control of attentional selection are poorly understood. Here, using a two-target free-choice luminance-reward selection task, we demonstrate that visual-movement neurons and not visual neurons or movement neurons encode exogenous and endogenous selection. We then show that coherent-beta activity selectively modulates mechanisms of exogenous selection specifically during conflict and consequently may support top-down control. These results reveal the VM-neuron-specific network mechanisms of attentional selection and suggest a functional role for beta-frequency coherent neural dynamics in the modulation of sensory communication channels for the top-down control of attentional selection.
Localization and connectivity of rodent equivalent of the primate posterior cingulate cortex (area 23)
Authors: Xiang Xiao-Jun , Chen Sheng-Qiang , Zhang Xue-Qin , Chen Chang-Hui , Zhang Shun-Yu , Cai Hui-Ru , Ding Song-Lin
Published: January 2023

The posterior cingulate cortex (mainly area 23) in human and non-human primates is a critical component of the default mode network and is involved in many neurological and neuropsychiatric diseases such as Alzheimer’s disease, autism, depression, attention deficit hyperactivity disorder and schizophrenia. However, cingulate area 23 has not yet identified in rodents and other lower mammals and this makes modeling related circuits and diseases in rodents very difficult. Using a comparative approach and unique connectional patterns the present study has uncovered the location and extent of rodent equivalent of the primate cingulate area 23. Like in monkeys, area 23 but not adjoining retrosplenial and visual areas in the rats and mice displays strong reciprocal connections with the anteromedial thalamic nucleus. Rodent area 23 also reciprocally connects with the medial pulvinar and claustrum as well as with the anterior cingulate, granular retrosplenial, medial orbitofrontal, postrhinal, and visual and auditory association cortices. The rodent A23 also projects to the subcortical effectors such as the dorsal striatum, ventral lateral geniculate nucleus, zona incerta, pretectal nucleus, superior colliculus, periaqueductal gray, and brainstem reticular formation. All these connectional findings support the versatility of area 23 in the integration and modulation of multimodal information underlying spatial processing, episodic memory, self-reflection, attention, value assessment and many adaptive behaviors. Additionally, this study also suggests that the rodents can be used to model primate and human area 23 in future structural, functional, pathological and neuromodulation studies.
Surgical, Anesthesia and Obstetrics (SAO) workforce production capacity in India: A retrospective analysis of postgraduate and sub-specialty training spots
Authors: Rao Shirish , Zadey Siddhesh
Published: January 2023

Objective

To assess the SAO production capacity of India i.e., the number of postgraduate (PG) and sub-specialty (SS) surgical training spots per 10 million population across multiple specialties and subspecialties at national and state levels.

Methods

A retrospective secondary data analysis of PG and SS SAO spots across 36 states for 2018 using data from the National Health Profile (2019) was conducted. The mid-year 2018 populations were obtained from the census-based population projections. The number of PG & SS SAO spots per 10 million population were calculated and divided based on the type of program (diploma, MD/MS & DM/MCh) and type of SAO specialty to investigate SAO workforce production capacity in each state. Ratios of PG spots per 100 MBBS spots and SS spots per 100 PG spots were also calculated. Data was wrangled using Google Sheets, analyzed in JASP v0.16.0.0, and visualized using Datawrapper.

Results

There are a total 13793 PG and 1350 SS SAO spots leading to densities of 104.60 and 9.90 per 10 million people, respectively. PG spot density for General Surgery (23.56), Anesthesia (24.81), and OBGYN (21.55) were comparable and were much higher than Orthopedics (14.64), Ophthalmology (11.96), and Otorhinolaryngology (8.08). SS spot densities were greater for Urology (1.90), Neurosurgery (1.86), and Cardiothoracic and Vascular Surgery (1.83), followed by Plastic Surgery (1.52), and Pediatric Surgery (1.27). The average density was significantly lower for PG SAO specialties than non-SAO specialties (p=0.001) whereas there was no significant difference in densities for SS SAO and non-SAO specialties (p=0.197). For 100 MBBS spots, there were only 20 PG SAO spots while for 100 PG SAO spots, there were just 9 SS SAO spots available. The distribution of spots was geographically uneven with about two-thirds of spots concentrated in 10 states/union territories.

Conclusion

Annually, India can produce only about 24 General Surgeons, 15 Orthopedic Surgeons, 12 Ophthalmologists, 8 Otorhinolaryngologists, 25 Anesthetists, 22 OBGYNs, and 10 sub-specialist surgeons per 10 million population. The distribution of spots is inequitable across the states. Hence, scale up of surgical training capacity needs to be carried out with attention to reducing disparities.

Highlights

We present a novel pan-India analysis of SAO workforce production capacity.

In 2018, India had 13793 postgraduate and 1350 subspecialty SAO training spots.

59 surgeons and 10 subspecialist surgeons are produced per 10 million people.

Competitiveness of matching into residency-level programs is assessed.

Every 100 MBBS spots had 20 PG SAO spots. Every 100 PG SAO spots had 9 SS SAO spots.
Non-negligible seroprevalence of murine typhus and its predictors in Japan: a large-scale seroepidemiological study
Authors: Aita Tetsuro , Sando Eiichiro , Katoh Shungo , Hamaguchi Sugihiro , Fujita Hiromi , Kurita Noriaki
Published: January 2023

Scrub typhus (ST) and Japanese spotted fever (JSF) are endemic rickettsioses in Japan, whereas murine typhus (MT) has been slightly reported over the last 50 years. To elucidate the epidemiology and risk factors of MT, we conducted a cross-sectional study of residents in the southern Boso Peninsula, a rickettsia-endemic region, from August to November 2020, using their sera, questionnaires, residential addresses, and geographic information. A total of 2,382 residents were included in the study. The seroprevalence of MT was higher than that of ST (11.3% vs. 7.9%), with a prevalence ratio of 1.42 (p<0.001). In addition, exposure to bushes and living in sparsely populated areas are significant risk factors for MT. These findings indicate that MT is a neglected disease; hence, patients with suspected rickettsial infections, especially those with risk factors, should undergo comprehensive rickettsial infection testing, including MT testing.

Article Summary Line

This is a large epidemiological study in Japan to elucidate the seroprevalence and predictors ofRickettsia typhi, which may be neglected today.
Area postrema neurons mediate interleukin-6 function in cancer-associated cachexia
Authors: Sun Qingtao , van de Lisdonk Daniëlle , Ferrer Miriam , Gegenhuber Bruno , Wu Melody , Tollkuhn Jessica , Janowitz Tobias , Li Bo
Published: January 2023

Interleukin-6 (IL-6) has been long considered a key player in cancer-associated cachexia1-15. It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia16-20. However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, mediate the function of IL-6 in cancer-associated cachexia in mice. We found that circulating IL-6 can rapidly enter the AP and activate AP neurons. Peripheral tumor, known to increase circulating IL-61-5,15,18,21-23, leads to elevated IL-6 and neuronal hyperactivity in the AP, and causes potentiated excitatory synaptic transmission onto AP neurons. Remarkably, neutralization of IL-6 in the brain of tumor-bearing mice with an IL-6 antibody prevents cachexia, reduces the hyperactivity in an AP network, and markedly prolongs lifespan. Furthermore, suppression ofIl6ra, the gene encoding IL-6 receptor, specifically in AP neurons with CRISPR/dCas9 interference achieves similar effects. Silencing of Gfral-expressing AP neurons also ameliorates the cancer-associated cachectic phenotypes and AP network hyperactivity. Our study identifies a central mechanism underlying the function of peripheral IL-6, which may serve as a target for treating cancer-associated cachexia.
Distributed representations of prediction error signals across the cortical hierarchy are synergistic
Authors: Gelens Frank , Äijälä Juho , Roberts Louis , Komatsu Misako , Uran Cem , Jensen Michael A. , Miller Kai J. , Ince Robin A.A. , Garagnani Max , Vinck Martin , Canales-Johnson Andres
Published: January 2023

An important question concerning inter-areal communication in the cortex is whether these interactions are synergistic, i.e. brain signals can either share common information (redundancy) or they can encode complementary information that is only available when both signals are considered together (synergy). Here, we dissociated cortical interactions sharing common information from those encoding complementary information during prediction error processing. To this end, we computed co-information, an information-theoretical measure that distinguishes redundant from synergistic information among brain signals. We analyzed auditory and frontal electrocorticography (ECoG) signals in five common awake marmosets performing two distinct auditory oddball tasks and investigated to what extent event-related potentials (ERP) and broadband (BB) dynamics encoded redundant and synergistic information during auditory prediction error processing. In both tasks, we observed multiple patterns of synergy across the entire cortical hierarchy with distinct dynamics. The information conveyed by ERPs and BB signals was highly synergistic even at lower stages of the hierarchy in the auditory cortex, as well as between auditory and frontal regions. Using a brain-constrained neural network, we simulated the spatio-temporal patterns of synergy and redundancy observed in the experimental results and further demonstrated that the emergence of synergy between auditory and frontal regions requires the presence of strong, long-distance, feedback and feedforward connections. These results indicate that the distributed representations of prediction error signals across the cortical hierarchy can be highly synergistic.
Observing Aggression Increases Aggression In Semi-Free Ranging Barbary Macaques
Authors: Blood Rachel A. , Semple Stuart
Published: January 2023

In many social living species, seeing conspecifics interacting can alter the behaviour of bystanders, leading to social contagion – the spread of behaviour or emotion among group members. Among primates, studies of a small number of species have explored bystanders’ responses to observing aggressive interactions, finding evidence that individuals that see such interactions are more likely to subsequently engage in aggressive behaviours themselves. To increase the taxonomic breadth of this body of research, working with semi-free ranging adult female Barbary macaques (Macaca sylvanus) at the Trentham Monkey Forest, Stoke-on-Trent, UK, we assessed bystanders’ responses to observing naturally occurring aggressive interactions. Data were collected under two conditions: (i) after observing an aggressive interaction between conspecifics and (ii) during a matched-control period, before which individuals did not observe aggression. Bystanders were significantly quicker to initiate an aggressive interaction themselves after observing an aggressive interaction than if they had not, providing evidence of behavioural contagion. There was no effect of observing aggression on the rates of self-directed behaviour (an indicator of anxiety), suggesting the negative emotional states associated with involvement in aggressive interactions did not spread to bystanders. The results of this study provide new insight into the nature and importance of visual contagion of behaviour among primates.
Engineered production of isoprene from the model green microalgaChlamydomonas reinhardtii
Authors: Yahya Razan Z. , Wellman Gordon B. , Overmans Sebastian , Lauersen Kyle J.
Published: January 2023

1.

Isoprene is a clear, colorless, volatile 5-carbon hydrocarbon that is one monomer of all cellular isoprenoids and a platform chemical with multiple applications in industry. Many plants have evolved isoprene synthases (IspSs) with the capacity to liberate isoprene from dimethylallyl pyrophosphate (DMAPP) as part of cellular protection mechanisms. Isoprene is hydrophobic and volatile, rapidly leaves plant tissues and is one of the main carbon emission sources from vegetation globally. The universality of isoprenoid metabolism allows volatile isoprene production from microbes expressing heterologous IspSs. Here, we compared heterologous overexpression from the nuclear genome and localization into the plastid of four plant terpene synthases (TPs) in the green microalgaChlamydomonas reinhardtii. Using sealed vial mixotrophic cultivation, direct quantification of isoprene production was achieved from the headspace of living cultures, with the highest isoprene production observed in algae expressing theIpomoea batatasIspS. Perturbations of the downstream carotenoid pathway through keto carotenoid biosynthesis enhanced isoprene titers, which could be further enhanced by increasing flux towards DMAPP through heterologous co-expression of a yeast isopentenyl-PP delta isomerase. Multiplexed controlled-environment testing revealed that cultivation temperature, rather than illumination intensity, was the main factor affecting isoprene yield from the engineered alga. This is the first report of heterologous isoprene production from a eukaryotic alga and sets a foundation for further exploration of carbon conversion to this commodity chemical.

Abstract Figure
Real-time feedback reduces participant motion during task-based fMRI
Authors: Rogers Chad S. , Jones Michael S. , McConkey Sarah , McLaughlin Drew J. , Peelle Jonathan E.
Published: January 2023

The potential negative impact of head movement during fMRI has long been appreciated. Although a variety of prospective and retrospective approaches have been developed to help mitigate these effects, reducing head movement in the first place remains the most appealing strategy for optimizing data quality. Real-time interventions, in which participants are provided feedback regarding their scan-to-scan motion, have recently shown promise in reducing motion during resting state fMRI. However, whether feedback might similarly reduce motion during task-based fMRI is an open question. In particular, it is unclear whether participants can effectively monitor motion feedback while attending to task-related demands. Here we assessed whether a combination of real-time and between-run feedback could reduce head motion during task-based fMRI. During an auditory word repetition task, 78 adult participants (aged 19–81) were pseudorandomly assigned to receive feedback or not. Feedback was provided FIRMM software that used real-time calculation of realignment parameters to estimate participant motion. We quantified movement using framewise displacement (FD). We found that motion feedback resulted in a statistically significant reduction in participant head motion, with a small-to-moderate effect size (reducing average FD from 0.347 to 0.282). Reductions were most apparent in high-motion events. We conclude that under some circumstances real-time feedback may reduce head motion during task-based fMRI, although its effectiveness may depend on the specific participant population and task demands of a given study.
The neural activity of auditory conscious perception
Authors: Christison-Lagay Kate L. , Freedman Noah C. , Micek Christopher , Khalaf Aya , Kronemer Sharif I. , Gusso Mariana M. , Kim Lauren , Forman Sarit , Ding Julia , Aksen Mark , Abdel-Aty Ahmad , Kwon Hunki , Markowitz Noah , Yeagle Erin , Espinal Elizabeth , Herrero Jose , Bickel Stephan , Young James , Mehta Ashesh , Wu Kun , Gerrard Jason , Damisah Eyiyemisi , Spencer Dennis , Blumenfeld Hal
Published: January 2023

Although recent work has made significant headway in understanding the temporal and spatial dynamics of the neural mechanisms of conscious perception, much of that work has focused on visual paradigms. To determine whether there are shared mechanisms for perceptual consciousness across sensory modalities, here we developed a task to test within the auditory domain. Participants (n=31) completed an auditory perceptual threshold task while undergoing intracranial electroencephalography (icEEG) for intractable epilepsy. Intracranial recordings from over 2,800 grey matter electrodes representing widespread cortical coverage were analyzed for power in the high gamma range (40–115 Hz)—a frequency range that reflects local neural activity. For trials that were perceived, we find activity in early auditory regions which is accompanied by activity in the right caudal middle frontal gyrus, and shortly thereafter by activity in non-auditory thalamus. This is followed by a wave of activity that sweeps through the higher auditory association regions and into parietal and frontal cortices, similar to the wave observed in our visual conscious perception paradigm. However, for not perceived trials, we find that significant activity is restricted to early auditory regions (and areas immediately adjacent to the Sylvian fissure). These findings show that the broad anatomical regions of cortical and subcortical networks involved in auditory perception are similar to the networks observed with vision, suggesting shared general mechanisms for conscious perception.
Interaction of FlhF, SRP-like GTPase with FliF, MS ring component assembling the initial structure of flagella in marineVibrio
Authors: Fukushima Yuria , Homma Michio , Kojima Seiji
Published: January 2023

Vibrio alginolyticusforms a single flagellum at its cell pole. FlhF and FlhG are known to be the main proteins responsible for the polar formation of single flagellum. FlhF, which belongs to the signal recognition particle (SRP)-type GTPase family, localizes at the cell pole and initiates flagellar generation. In contrast, FlhG negatively regulates flagellar numbers. Furthermore, MS-ring formation in the flagellar basal body appears to be an initiation step for flagellar assembly. The MS-ring is formed by a single protein, FliF, which has two transmembrane (TM) segments and a large periplasmic region. We had shown that FlhF was required for the polar localization ofVibrioFliF, and FlhF facilitated MS-ring formation when FliF was overexpressed inE. colicells. These results suggest that FlhF interacts with FliF to facilitate MS-ring formation. Here, we attempted to detect this interaction usingVibrioFliF fragments fused to a tag of Glutathione S-transferase (GST) inE. coli. We found that the N-terminal 108 residues of FliF, including the first TM segment and the periplasmic region, could pull FlhF down. In the first step, the SRP and its receptor are involved in the transport of membrane proteins to target them, which delivers them to the translocon. FlhF may have a similar or enhanced function as SRP, which binds to a region rich in hydrophobic residues.

IMPORTANCE

Vibrio alginolyticusforms only a single flagellum at the cell pole by regulators of FlhF and FlhG. FlhF regulates positively the formation of flagella and is required for polar positioning of the flagellum. FliF, the two transmembrane (TM) segments and a large periplasmic region, forms the MS ring of flagellar basal body in the membrane. Previous studies suggest that FlhF interacts with FliF to facilitate MS ring formation at the cell pole, but the interaction has not been detected. Here, we show the evidence that FlhF interacts with FliF at residues including the first TM segment and following periplasmic region. The hydrophobic residues of this region seem to be important for the interaction.
Redox-active compound generated by bacterial crosstalk induces hypha branching inStreptomycesspecies
Authors: Kato Manami , Asamizu Shumpei , Onaka Hiroyasu
Published: January 2023

Chemical cross talks betweenMycolicibacterium septicumHEK138M andBacillus subtilis168 affect the bacterial morphology ofStreptomyces variegatusHEK138A. We found thatS. variegatusexhibits unusual hyphae branching by the bacterial interaction. We aimed to elucidate the mechanism by performing activity guided purification of substances that induce the unusual cell morphology. We found that pyrogallol, a redox active aromatic small molecule induced significant hyphae branching inS. variegatusand the activity was also observed in some of otherStreptomycesspecies. Interestingly, the pyrogallol activity was diminished by adding catalase, which broke down H2O2. To further confirm the involvement, H2O2was tested and similar activity which induced hyphal branching was observed. This indicates that reactive oxygen species (ROS) generated by redox-active compound (RAC) is the inducing factor of hyphae branching. Further investigation revealed that pyrogallol was generated by NahG enzyme homolog ofM. septicumusing 2,3-dihydroxybenzoic acid as substrate by heterologous expression inE. coli. Moreover, co-culture with gene knock-out mutants revealed that 2,3-dihydroxybenzoic acid was supplied byB. subtilisproduced as intermediate of bacterial siderophore bacillibactin. Since the hyphae branching of vegetative mycelium can increase the density of filamentous network and consequently help secure the milieu in soil, our results suggested that those filamentous soil bacteria use ROS which can be supplied from plant derived RAC as a signal. As those RAC ubiquitously exist in soil environment, the system will be beneficial for sensing the nutrient sources in addition to the generally considered defensive response to oxidative stress.

Importance

The characterization of interactions between three or more bacteria are lacking as these interactions are visually imperceptible in general. Our current study revealed changes of morphological behavior by the bacterial interaction. This study showed that hydrogen peroxide generated by redox-active compound derived from a breakdown product of siderophore can significantly increase the number of hyphae tip extension in filamentous bacteria. Our result implies the existence of oxidative response system using a low amount of reactive oxygen species as an integrated signal to sense the plant-derived carbon source by the filamentous soil bacteria. As a result of sensing, filamentous soil bacteria may decide whether the hypha tip should be extended to further explore the area or increase the tips to densify filamentous network to monopolize the nutrients in the milieu.
Gait event prediction from surface electromyography in parkinsonian patients
Authors: Haufe Stefan , Isaias Ioannis U. , Pellegrini Franziska , Palmisano Chiara
Published: January 2023

Gait disturbances are common manifestations of Parkinson’s disease (PD), with unmet therapeutic needs. Inertial measurement units (IMU) are capable of monitoring gait, but they lack neurophysiological information that may be crucial for studying gait disturbances in these patients. Here, we present a machine-learning approach to approximate IMU angular velocity profiles, and subsequently gait events from electromyographic (EMG) channels. We recorded six parkinsonian patients while walking for at least three minutes. Patient-agnostic regression models were trained on temporally-embedded EMG time series of different combinations of up to five leg muscles bilaterally (i.e., tibialis anterior, soleus, gastrocnemius medialis, gastrocnemius lateralis, and vastus lateralis). Gait events could be detected with high temporal precision (median displacement <50 msec), low numbers of missed events (<2%), and next to no false positive event detections (<0.1%). Swing and stance phases could thus be determined with high fidelity (median F1 score ∼0.9). Interestingly, the best performance was obtained using as few as two EMG probes placed on the left and right vastus lateralis. Our results demonstrate the practical utility of the proposed EMG-based system for gait event prediction while allowing the simultaneous acquisition of an electromyographic signal. This gait analysis approach has the potential to make additional measurement devices such as IMU and force plates less essential, and thereby to reduce financial and preparation overheads and discomfort factors in gait studies.
Differences in site-specific cancer incidence by individual- and area-level income in Canada from 2006-2015
Authors: Tope Parker , Morais Samantha , El-Zein Mariam , Franco Eduardo L. , Malagón Talía
Published: January 2023

Introduction

Income, a component of socioeconomic status, influences cancer risk as a social determinant of health. We evaluated the independent associations between individual- and area-level income, and site-specific cancer incidence in Canada.

Methods

We used data from the 2006 and 2011 Canadian Census Health and Environment Cohorts, which are probabilistically linked datasets constituted by 5.9 million and 6.5 million respondents of the 2006 Canadian long-form census and 2011 National Household Survey, respectively. Individuals were linked to the Canadian Cancer Registry through 2015. Individual-level income was derived using after-tax household income adjusted for household size. Annual tax return postal codes were used to assign area-level household income quintiles to individuals for each year of follow-up. We calculated age-standardized incidence rates (ASIR) and rate ratios for cancers overall and by site. We conducted multivariable negative binomial regression to adjust these rates for other demographic and socioeconomic variables.

Results

Individuals of lower individual- and area-level income had higher ASIRs compared to those in the wealthiest income quintile for head and neck, oropharyngeal, esophageal, stomach, colorectal, anal, liver, pancreas, lung, cervical, and kidney and renal pelvis cancers. Conversely, individuals of wealthier individual- and area-level income had higher ASIRs for melanoma, leukemia, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma, breast, uterine, prostate, and testicular cancers. Most differences in site-specific incidence by income quintile remained after adjustment.

Conclusions

Although Canada’s publicly funded healthcare system provides universal coverage, inequalities in cancer incidence persist across individual- and area-level income gradients. Our estimates suggest that individual- and area-level income affect cancer incidence through independent mechanisms.
Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders
Authors: Denis Jessica , Garnier Annabelle , Cheutin Laurence , Ferrier Audrey , Timera Hawa , Jarjaval Fanny , Hejl Carine , Billon-Denis Emmanuelle ,   Percy ImmunoCovid group, Ricard Damien , Tournier Jean-Nicolas , Trignol Aurélie , Mura Marie
Published: January 2023

Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission. We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer). While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19, and could potentially be used as an early prognosis biomarker.
Coverage of primary and booster vaccination against COVID-19 by socioeconomic level: A nationwide cross-sectional registry study
Authors: Hansen Bo T , Labberton Angela S , Kour Prabhjot , Kraft Kristian B
Published: January 2023

High and equitable COVID-19 vaccination coverage is important for pandemic control and prevention of health inequity. However, little is known about socioeconomic correlates of booster vaccination coverage. In this cross-sectional study of all Norwegian adults in the national vaccination program (N = 4,190,655), we use individual-level registry data to examine coverage by levels of household income and education of primary (≥2 doses) and booster (≥3 doses) vaccination against COVID-19. We stratify the analyses by age groups with different booster recommendations and report relative risk ratios (RR) for vaccination by 25 August 2022. In the 18-44 years group, individuals with highest vs. lowest education had 94% vs. 79% primary coverage (adjusted RR (adjRR) 1.15, 95%CI 1.14-1.15) and 67% vs. 38% booster coverage (adjRR 1.55, 95% CI 1.55-1.56), while individuals with highest vs. lowest income had 94% vs. 81% primary coverage (adjRR 1.10, 95%CI 1.10-1.10) and 60% vs. 43% booster coverage (adjRR 1.23, 95%CI 1.22-1.24). In the≥45 years group, individuals with highest vs. lowest education had 96% vs. 92% primary coverage (adjRR 1.02, 95%CI 1.02-1.02) and 88% vs. 80% booster coverage (adjRR 1.09, 95%CI 1.09-1.09), while individuals with highest vs. lowest income had 98% vs. 82% primary coverage (adjRR 1.16, 95%CI 1.16-1.16) and 92% vs. 64% booster coverage (adjRR 1.33, 95%CI 1.33-1.34). In conclusion, we document large socioeconomic inequalities in COVID-19 vaccination coverage, especially for booster vaccination, even though all vaccination was free-of-charge. The results highlight the need to tailor information and to target underserved groups for booster vaccination.
Automated Prognosis of Renal Function Decline in ADPKD Patients using Deep Learning
Authors: Raj Anish , Tollens Fabian , Caroli Anna , Nörenberg Dominik , Zöllner Frank G.
Published: January 2023

The prognosis of renal function decline in Autosomal Dominant Polycystic Kidney Disease (ADPKD) is vital for early intervention. Currently, the accepted biomarkers are height-adjusted total kidney volume (HtTKV) with estimated glomerular filtration rate (eGFR) and patient age. However, kidney volume delineation is time-consuming and prone to observer variability. Furthermore, improvement in prognosis can be achieved by incorporating automatically generated features of kidney MRI images in addition to the conventional biomarkers. Hence, to improve prediction we develop two deep learning algorithms. At first, we create an automated kidney volume segmentation model that can accurately calculate HtTKV. Secondly, we use the segmented kidney volumes with the predicted HtTKV, age, and eGFR at the baseline visit. Here, we use a combination of convolutional neural network (CNN) and multi-layer perceptron (MLP) for the prediction of chronic kidney disease (CKD) stages >=3A, >=3B, and a 30% decline in eGFR after 8 years from the baseline visit. We obtain AUC scores of 0.96, 0.96, and 0.95 for CKD stages >=3A, >=3B, and 30% decline in eGFR, respectively. Moreover, our algorithm achieves a Pearson correlation coefficient of 0.81 between predicted and measured eGFR decline. We further extend our approach to predict distinct CKD stages after eight years with high accuracy. The proposed approach might improve monitoring and support the prognosis of ADPKD patients from the earliest disease stages.
Variations in COVID-19 impacts by social vulnerability in Philadelphia, June 2020-December 2022
Authors: Strelau Katherine M. , Feuerstein-Simon Rachel , Naseer Nawar , Lang Megan , Rix Kevin , Murray Eleanor J , Morris Jeffrey S. , Wiebe Douglas J. , Nelson Hillary C.M. , Collman Ronald G. , Rodino Kyle G. , Bushman Frederic D. , Kelly Brendan J. , Cannuscio Carolyn C.
Published: January 2023

Introduction

The study objective was to elucidate the relationship between social vulnerability and COVID-19 impacts in Philadelphia over a 2.5-year period, between June 2020 and December 2022.

Methods

Using publicly available COVID-19 case, test, hospitalization, and mortality data for Philadelphia (June 7, 2020-December 31, 2022) and area-level social vulnerability data, we compared the incidence, test positivity, hospitalization, and mortality rates in high and low vulnerability neighborhoods of Philadelphia, characterized as scoring above or below the national median score on the social vulnerability index. We used linear mixed effects models to test the association between social vulnerability and COVID-19 incidence, test positivity, hospitalization, and mortality rates, adjusting for time and age distribution.

Results

90.4% of Philadelphians (n= 1,430,153) live in neighborhoods classified as socially vulnerable, based on scoring above the national median score on the social vulnerability index. COVID-19 incidence, hospitalization, and mortality rates were significantly elevated in the more vulnerable communities, withp< 0.05,p< 0.005, andp< 0.001, respectively. The relative risks of COVID-19-related incidence, hospitalization, and death, comparing the more vulnerable neighborhoods to the less vulnerable neighborhoods, were 1.11 (95%CI: 1.10-1.12), 2.07 (95%CI: 1.93-2.20), and 2.06 (95%CI: 1.78-2.38), respectively. Thus, between June 7, 2020 and December 31, 2022, 32,573 COVID-19 cases, 9,409 hospitalizations, and 1,967 deaths would have been avoided in Philadelphia’s more vulnerable communities had they experienced the same rates of incidence, hospitalization, and death as the less vulnerable Philadelphia communities.

Conclusions

These results highlight the disparate morbidity and mortality experienced by people living in more vulnerable neighborhoods in a large US city. Importantly, our findings illustrate the importance of designing public health policies and interventions with an equity-driven approach, with greater resources and more intensive prevention strategies applied in socially vulnerable communities.
Speos: An ensemble graph representation learning framework to predict core genes for complex diseases
Authors: Ratajczak Florin , Joblin Mitchell , Hildebrandt Marcel , Ringsquandl Martin , Falter-Braun Pascal , Heinig Matthias
Published: January 2023

Understanding phenotype-to-genotype relationships is a grand challenge of 21st century biology with translational implications. The recently proposed “omnigenic” model postulates that effects of genetic variation on traits are mediated bycore-genes and -proteins whose activities mechanistically influence the phenotype, whereasperipheralgenes encode a regulatory network that indirectly affects phenotypes via core gene products. We have developed a positive-unlabeled graph representation-learning ensemble-approach to predict core genes for diverse diseases using Mendelian disorder genes for training. Employing mouse knockout phenotypes for external validation, we demonstrate that our most confident predictions validate at rates on par with the Mendelian disorder genes, and all candidates exhibit core-gene properties like transcriptional deregulation in diseases and loss-of-function intolerance. Predicted candidates are enriched for drug targets and druggable proteins and, in contrast to Mendelian disorder genes, also for druggable but yet untargeted gene products. Model interpretation suggests key molecular mechanisms and physical interactions for core gene predictions. Our results demonstrate the potential of graph representation learning and pave the way for studying core gene properties and future drug development.
Comparison of metabarcoding taxonomic markers to describe fungal communities in fermented foods
Authors: Rué Olivier , Coton Monika , Dugat-Bony Eric , Howell Kate , Irlinger Françoise , Legras Jean-Luc , Loux Valentin , Michel Elisa , Mounier Jérôme , Neuvéglise Cécile , Sicard Delphine
Published: January 2023

Abstract

Next generation sequencing offers several ways to study microbial communities. For agri-food sciences, identifying species in diverse food ecosystems is key for both food sustainability and food security. The aim of this study was to compare metabarcoding pipelines and markers to determine fungal diversity in food ecosystems, from Illumina short reads. We built mock communities combining the most representative fungal species in fermented meat, cheese, wine and bread. Four barcodes (ITS1, ITS2, D1/D2 and RPB2) were tested for each mock and on real fermented products. We created a database, including all mock species sequences for each barcode to compensate for the lack of curated data in available databases. Four bioinformatics tools (DADA2, QIIME, FROGS and a combination of DADA2 and FROGS) were compared. Our results clearly showed that the combined DADA2 and FROGS tool gave the most accurate results. Most mock community species were not identified by the RPB2 barcode due to unsuccessful barcode amplification. When comparing the three rDNA markers, ITS markers performed better than D1D2, as they are better represented in public databases and have better specificity to distinguish species. Between ITS1 and ITS2, differences in the best marker were observed according to the studied ecosystem. While ITS2 is best suited to characterize cheese, wine and fermented meat communities, ITS1 performs better for sourdough bread communities. Our results also emphasized the need for a dedicated database and enriched fungal-specific public databases with novel barcode sequences for 118 major species in food ecosystems.