bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic testing and the evolution of detection avoidance by pathogens
Authors: Wood Jason , Ashby Ben 
Published: September 2023

AbstractDiagnostic testing is a key tool in the fight against many infectious diseases. The emergence of pathogen variants that are able to avoid detection by diagnostic testing therefore represents a key challenge for public health. In recent years, variants for multiple pathogens have emerged which escape diagnostic testing, including mutations inPlasmodium falciparum(malaria),Chlamydia trachomatis(chlamydia) and SARS-CoV-2 (COVID-19). However, little is currently known about when and the extent to which diagnostic test escape will evolve. Here we use a mathematical model to explore how the frequency of diagnostic testing, combined with variation in compliance and efficacy of quarantining, together drive the evolution of detection avoidance. We derive key thresholds under which a testing regime will (i) select for diagnostic test avoidance, or (ii) drive the pathogen extinct. Crucially, we show that imperfect compliance with diagnostic testing regimes can have marked effects on selection for detection avoidance, and consequently, for disease control. Yet somewhat counterintuitively, we find that an intermediate level of testing can select for the highest level of detection avoidance. Our results, combined with evidence from various pathogens, demonstrate that the evolution of diagnostic testing avoidance should be carefully considered when designing diagnostic testing regimes.
Transcutaneous auricular vagus nerve stimulation enhanced inhibitory control via increasing intrinsic prefrontal couplings
Authors: Zhu Siyu , Liu Qi , Zhang Xiaolu , Zhou Menghan , Zhou Xinqi , Ding Fangyuan , Zhang Rong , Becker Benjamin , Kendrick Keith M , Zhao Weihua 
Published: September 2023

AbstractInhibitory control represents a core executive function that critically facilitates adaptive behavior and survival in an ever-changing environment. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been hypothesized to improve behavioral inhibition performance, however the neurocomputational mechanism of taVNS-induced neuroenhancement remain elusive. In the current study, we investigated the effect of taVNS on inhibitory control in a pre-registered sham-controlled between-subject functional near infrared spectroscopy (fNIRS) experiment with an emotional face Go/No-Go paradigm in ninety subjects. After data quality check, eighty-two subjects were included in the final data analysis. Behaviorally, the taVNS improved No-Go response accuracy, together with computational modeling using Hierarchical Bayesian estimation of the Drift Diffusion Model (HDDM) indicating that it specifically reduced the information accumulation rate for Go responses, and this was negatively associated with increased accuracy of No-Go responses. On the neural level, taVNS enhanced engagement of the bilateral inferior frontal gyrus (IFG) during inhibition of angry expression faces and modulated functional couplings (FCs) within the prefrontal inhibitory control network. Mediation models revealed that taVNS-induced facilitation of inhibitory control was critically mediated by a decreased information accumulation for Go responses and concomitantly enhanced neurofunctional coupling between the inferior and orbital frontal cortex. Our findings demonstrate a striking potential for taVNS to improve inhibitory control via reducing pre-potent responses and enhancing FCs within prefrontal inhibitory control networks, suggesting a promising therapeutic role in treating specific disorders characterized by inhibitory control deficits.
bistro: An R package for vector bloodmeal identification by short tandem repeat overlap
Authors: Lapp Zena , Abel Lucy , Mangeni Judith , Obala Andrew A. , O’Meara Wendy , Taylor Steve M. , Markwalter Christine F. 
Published: September 2023

AbstractMeasuring vector-human contact in a natural setting can inform precise targeting of interventions to interrupt transmission of vector-borne diseases. One approach is to directly match human DNA in vector bloodmeals to the individuals who were bitten using genotype panels of discriminative short tandem repeats (STRs). Existing methods for matching STR profiles in bloodmeals to the people bitten preclude the ability to match most incomplete profiles and multi-source bloodmeals to bitten individuals.We developed bistro, an R package that implements 3 preexisting STR matching methods as well as the package’s namesake, bistro, a new algorithm described here. bistro employs forensic analysis methods to calculate likelihood ratios and match human STR profiles in bloodmeals to people using a dynamic threshold. We evaluated the algorithm’s accuracy and compared it to existing matching approaches using a publicly-available panel of 188 single-source and 100 multi-source samples containing DNA from 50 known human sources. Then we applied it to match 777 newly field-collected mosquito bloodmeals to a database of 645 people.The R package implements four STR matching algorithms in user-friendly functions with clear documentation. bistro correctly matched 99% (184/185) of profiles in single-source samples, and 63% (225/359) of profiles from multi-source samples, resulting in a sensitivity of 0.75 (vs < 0.51 for other algorithms). The specificity of bistro was 0.9998 (vs. 1 for other algorithms). Furthermore, bistro identified 80% (729/909) of all possible matches for field-derived mosquitoes, yielding 1.4x more matches than existing algorithms.bistro identifies more correct bloodmeal-human matches than existing approaches, enabling more accurate and robust analyses of vector-human contact in natural settings. The bistro R package and corresponding documentation allow for straightforward uptake of this algorithm by others.
Differential LRRK2 signalling and gene expression in WT-LRRK2 and G2019S-LRRK2 mouse microglia treated with zymosan and MLi2
Authors: Nazish Iqra , Mamais Adamantios , Mallach Anna , Bettencourt Conceicao , Kaganovich Alice , Warner Tom , Hardy John , Lewis Patrick A. , Pocock Jennifer , Cookson Mark R , Bandopadhyay Rina 
Published: September 2023

AbstractIntroductionMutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene cause autosomal dominant Parkinson’s disease (PD) with the most common causative mutation being theLRRK2p.G2019S within the kinase domain. LRRK2 protein is highly expressed in the human brain and also in the periphery, and high expression of dominant PD genes in immune cells suggest involvement of microglia and macrophages in inflammation related to PD. LRRK2 is known to respond to extracellular signalling including TLR4 resulting in alterations in gene expression, with the response to TLR2 signalling through zymosan being less known.MethodsHere, we investigated the effects of zymosan, a TLR2 agonist and the potent and specific LRRK2 kinase inhibitor MLi-2 on gene expression in microglia fromLRRK2-WTandLRRK2p.G2019S knock-in mice by RNA-Sequencing analysis.ResultsWe observed both overlapping and distinct zymosan and MLi-2 mediated gene expression profiles in microglia. At least two candidate Genome-Wide Association (GWAS) hits for PD, CathepsinB (Ctsb) and Glycoprotein-nmb (Gpnmb), were notably downregulated by zymosan treatment. Genes involved in inflammatory response and nervous system development were up and downregulated respectively with zymosan treatment while MLi-2 treatment particularly exhibited upregulated genes for ion transmembrane transport regulation. Furthermore, we observed the top twenty most significantly differentially expressed genes inLRRK2p.G2019S microglia show enriched biological processes in iron transport and response to oxidative stress.DiscussionOverall, these results suggest that microglial LRRK2 may contribute to PD pathogenesis through altered inflammatory pathways. Our findings should encourage future investigations of these putative avenues in the context of PD pathogenesis.
A taxonomically informed DNA reference library to facilitate future biodiversity assessments and monitoring: a case study using seaweeds along a tropical-temperate transition zone in South Africa
Authors: Reddy Maggie M. , du Plessis Jamie , Anderson Robert J. , Roodt-Wilding Rouvay , Bolton John J. 
Published: September 2023

AbstractThe role of seaweeds in the blue bioeconomy has stimulated research efforts around the world but proper species identification and biodiversity assessments, remain a challenge. The South African coast hosts the confluence of the Indian Ocean and Atlantic Ocean, creating a dynamic evolutionary environment that has over time yielded a rich diversity of seaweeds with the highest seaweed diversity occurring along the Agulhas Marine Province. Although South Africa harbours one of the richer seaweed floras in the world, only 24% of the known species are represented by DNA barcodes. We therefore initiated the construction of a taxonomically guided DNA reference library for seaweeds in South Africa with the aim of continuously adding to it in the future. To do this, a seaweed biodiversity survey of the Rhodophyta occurring along a temperate-tropical biogeographic transition zone situated within the Agulhas Marine Province (AMP) in South Africa was carried out. Seaweeds were identified in the field using available field or taxonomic guides and herbarium vouchers were prepared. Subsamples were preserved for DNA analyses and three DNA barcodes (LSU D2-D3;rbcL-3P; COI 5P) were amplified. Sequences were verified on BLAST and preliminary phylogenetic analyses or comparison with the literature were carried out where necessary. A total of 220 barcodes was generated for 88 species and one species variety, including 17 species from or near their type localities and eight generitypes. Novel barcodes were generated for 73 species, nearly half of which were species endemic to Southern Africa. In addition, 21 taxa representing new, potentially new, or reinstated species and at least two new genera were identified as well as one new distribution recorded, all of which require further study. This study significantly adds to the foundational biodiversity knowledge of the South African seaweed flora and highlights new avenues for further research.
Legionella felix sp. - A novel Legionella species isolated in Israel from hot tap water
Authors: Valenci Gal Zizelski , Ohad Shosanit , Robinstein Mor , Assaly Shereen , Kutikov Ina , Groisman Ludmila , Murik Omer , Zeevi David A. , David Ravid Ben , Farber Alona , Dveyrin Zeev , Rorman Efrat , Nissan Israel 
Published: September 2023

AbstractBacteria of the genusLegionellaare natural pathogens of the environment that can cause legionellosis, which can result in severe human pneumonia called Legionnaires’ disease. Here we describe a novelLegionellaspecies isolated from hot tap water. High quality complete genome was generated using a combination of Nanopore and Illumina sequencing approaches. Our novelLegionellaisolate possesses a 3,913,681 bp chromosome, (GC content 38.78% Mol) and a single novel largeincFconjugative plasmid of 160,500 bp (GC content 37.97%). Interestingly, the chromosome encodes for 14 secondary metabolites biosynthetic gene clusters, more than any known otherLegionellasp. The novel plasmid encodes for multiple genes that confer resistance to heavy metals. Bioinformatics analysis including average nucleotide identity (ANI) and genome-based taxonomy computation revealed that the genome of the new isolate differs from any previously describedLegionellaspecies. The closest related species to our isolate isLegionella cherrii. The name proposed for the new specie isLegionella felixin honor of Dr. Arthur Felix (1887-1956), a pioneering microbiologist, and member of the Royal Society of UK, who established the National Public Health Laboratory in Tel Aviv.
The ALDH1A3 Reporter Construct: A Novel Mechanism of Identifying and Tracking the Breast Cancer Stem Cell Population
Authors: Philbin Nick , Laurie Ellen M. , Fifield Bre-Anne , Porter Lisa Ann 
Published: September 2023

AbstractCancer stem cells lie at the heart of progression and relapse for many solid tumours including breast cancers. The Breast Cancer Stem Cell (BCSC) population is typically isolated via a combination of markers utilizing various staining techniques which prevents the ability to track dynamic changes in expression and to dissect the role in pathogenesis overtime. Here we report the development of a reporter for the expression of Aldehyde Dehydrogenase 1A3 (ALDH1A3), a marker of high clinical importance in many breast cancers, and other solid tumours. BCSCs displaying increased transcriptional activation of ALDH1A3 demonstrate an increase in self-renewal capabilities. This tool improves the ability to reliably follow select cancer stem cell populations over time.
Understanding Neuromodulation Pathways in tDCS: Brain Stem Recordings in Rat During Trigeminal Nerve Direct Current Stimulation
Authors: Majdi Alireza , Asamoah Boateng , Mc Laughlin Myles 
Published: September 2023

AbstractBackgroundRecent evidence suggests that transcranial direct current stimulation (tDCS) indirectly influences brain activity through cranial nerve pathways, particularly the trigeminal nerve. However, the electrophysiological effects of direct current (DC) stimulation on the trigeminal nerve (DC-TNS) and its impact on trigeminal nuclei remain unknown. These nuclei exert control over brainstem centers regulating neurotransmitter release, such as serotonin and norepinephrine, potentially affecting global brain activity.ObjectivesTo investigate how DC-TNS impacts neuronal activity in the principal sensory nucleus (NVsnpr) and the mesencephalic nucleus of the trigeminal nerve (MeV).MethodsTwenty male Sprague Dawley rats (n=10 each nucleus) were anesthetized with urethane. DC stimulation, ranging from 0.5 to 3 mA, targeted the trigeminal nerve’s marginal branch. Simultaneously, single-unit electrophysiological recordings were obtained using a 32-channel silicon probe, comprising three one-minute intervals: pre-stimulation, DC stimulation, and post-stimulation. Xylocaine was administered to block the trigeminal nerve as a control.ResultsDC-TNS significantly increased neuronal spiking activity in both NVsnpr and MeV, returning to baseline during the post-stimulation phase. When the trigeminal nerve was blocked with xylocaine, the robust 3 mA trigeminal nerve DC stimulation failed to induce increased spiking activity in the trigeminal nuclei.ConclusionOur results offer initial empirical support for trigeminal nuclei activity modulation via DC-TNS. This discovery supports the hypothesis that cranial nerve pathways may play a pivotal role in mediating tDCS effects, setting the stage for further exploration into the complex interplay between peripheral nerves and neural modulation techniques.HighlightsDirect current stimulation of the trigeminal nerve (DC-TNS) modulates neural activity in rat NVsnpr and MeV.Xylocaine administration reversibly blocks the DC-TNS effect on neural responses.Trigeminal nerve stimulation should be considered a possible mechanism of action of tDCS.
Zinc is Essential for the Copper Reductase Activity of Yeast Nucleosomes
Authors: Vogelauer Maria , Cheng Chen , Karimian Ansar , Iranpour Hooman Golshan , Kurdistani Siavash K. 
Published: September 2023

AbstractThe histone H3-H4 tetramer is a copper reductase enzyme, facilitating the production of cuprous (Cu1+) ions for distribution to copper-dependent enzymes. It was, however, unknown if this enzymatic activity occurred within nucleosomes. To investigate this, we obtained native nucleosomes fromSaccharomyces cerevisiaeusing micrococcal nuclease digestion of chromatin in isolated nuclei and ion-exchange chromatographic purification. The purified nucleosomal fragments robustly reduced Cu2+to Cu1+ions, with the optimal activity dependent on the presence of zinc ions. Mutation of the histone H3 histidine 113 (H3H113) residue at the active site substantially reduced the enzymatic activity of nucleosomes, underscoring the catalytic role of histone H3. Consistently, limiting zinc ions reduced intracellular Cu1+levels and compromised growth, phenotypes that were mitigated by genetically enhancing the copper reductase activity of histone H3. These results indicate that yeast nucleosomes possess copper reductase activity, suggesting that the fundamental unit of eukaryotic chromatin is an enzyme complex.
GABA Release From Central Amygdala Neurotensin Neurons Differentially Modulates Reward and Consummatory Behavior in Male and Female Mice
Authors: Gereau Graydon B. , Torruella-Suárez María L. , Sizer Sarah E. , Xia Mengfan , Zhou Diana , Wykoff Luke A. , Teklezghi Adonay T. , Alvarez-Pamir Ali , Boyt Kristen M. , Kash Thomas L. , McElligott Zoé A. 
Published: September 2023

AbstractThe central nucleus of the amygdala is known to play key roles in alcohol use and affect. Neurotensin neurons in the central nucleus of the amygdala have been shown to regulate alcohol drinking in male mice. However, little is known about which neurotransmitters released by these cells drive alcohol consumption or whether these cells drive alcohol consumption in female mice. Here we show that knockdown of GABA release from central amygdala neurotensin neurons using aNts-cre-dependent vGAT-shRNA-based AAV strategy reduces alcohol drinking in male, but not female, mice. This manipulation did not impact avoidance behavior, except in a fasted novelty-suppressed feeding test, in which vGAT shRNA mice demonstrated increased latency to feed on a familiar high-value food reward, an effect driven by male mice. In contrast, vGAT shRNA female mice showed heightened sensitivity to thermal stimulation. These data show a role for GABA release from central amygdala neurotensin neurons in modulating consumption of rewarding substances in different motivational states.
Wnt signaling and contact-mediated repulsion shape sensory dendritic fields
Authors: Tzeng Christopher P. , Shen Kang 
Published: September 2023

AbstractThe complete and non-redundant coverage of sensory tissues by neighboring neurons enables effective detection of stimuli in the environment. How the neurites of adjacent neurons establish their boundaries to achieve this completeness in coverage remains incompletely understood. Here, we use distinct fluorescent reporters to study two neighboring sensory neurons with complex dendritic arbors, FLP and PVD, inC. elegans. We quantify the sizes of their dendritic fields, and identify CWN-2/Wnt and LIN-17/Frizzled as a ligand and receptor that regulate the relative dendritic field sizes of these two neurons. Loss of eithercwn-2orlin-17results in complementary changes in the size of the dendritic fields of both neurons; the FLP arbor expands, while that of PVD shrinks. Using an endogenous knock-in mNeonGreen-CWN-2/Wnt, we find that CWN-2/Wnt is localized along the path of growing FLP dendrites. Dynamic imaging shows a significant braking of FLP dendrite growth upon CWN-2/Wnt contact. We find that LIN-17/Frizzled functions cell-autonomously in FLP to limit dendritic field size and propose that PVD fills the space left by FLP through contact-induced retraction. Our results reveal that interactions of dendrites with adjacent dendrites and with environmental cues both shape the boundaries of neighboring dendritic fields.Highlights▫Secreted Wnt CWN-2 and cell-autonomous activity of neuronal LIN-17/Frizzled receptors restrict FLP dendritic field sizes▫Endogenously tagged CWN-2/Wnt is punctate and visible in the same plane of growing FLP dendrites▫Growth of developing FLP dendrites is inhibited upon contact with extracellular CWN-2/Wnt and with PVD dendrites
Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics
Authors: Ose Nicholas J. , Campitelli Paul , Modi Tushar , Kazan I. Can , Kumar Sudhir , Ozkan S. Banu 
Published: September 2023

AbstractWe integrate evolutionary predictions based on the neutral theory of molecular evolution with protein dynamics to generate mechanistic insight into the molecular adaptations of the SARS-COV-2 Spike (S) protein. With this approach, we first identified Candidate Adaptive Polymorphisms (CAPs) of the SARS-CoV-2 Spike protein and assessed the impact of these CAPs through dynamics analysis. Not only have we found that CAPs frequently overlap with well-known functional sites, but also, using several different dynamics-based metrics, we reveal the critical allosteric interplay between SARS-CoV-2 CAPs and the S protein binding sites with the human ACE2 (hACE2) protein. CAPs interact far differently with the hACE2 binding site residues in the open conformation of the S protein compared to the closed form. In particular, the CAP sites control the dynamics of binding residues in the open state, suggesting an allosteric control of hACE2 binding. We also explored the characteristic mutations of different SARS-CoV-2 strains to find dynamic hallmarks and potential effects of future mutations. Our analyses reveal that Delta strain-specific variants have non-additive (i.e., epistatic) interactions with CAP sites, whereas the less pathogenic Omicron strains have mostly additive mutations. Finally, our dynamics-based analysis suggests that the novel mutations observed in the Omicron strain epistatically interact with the CAP sites to help escape antibody binding.
Synergistic action of actin binding proteins regulate actin network organization and cell shape
Authors: Serres Murielle P. , Smith Matthew B. , Lavoie Geneviève , Roux Philippe P. , Paluch Ewa K. 
Published: September 2023

AbstractAnimal cell shape is largely determined by the organization of the actin cytoskeleton. Spread shapes result from a balance between protrusive actin networks and contractile stress fibers, while rounded shapes are supported by a contractile actomyosin cortex. The assembly and regulation of distinct types of actin networks have been extensively studied, yet, what determines which networks dominate in a given cell remains unclear. In this Brief Report, we explore the molecular regulation of overall actin organization and resulting cell shape. We use our recently published comparison of the F-actin interactome in spread interphase and rounded mitotic cells to establish a list of candidate regulators of actin networks in spread cells. Utilizing micropatterning and automated image analysis we quantitatively analyze how these candidates affect actin organization. Out of our initial 16 candidates, we identify subsets of proteins promoting stress fibers or regulating their arrangement. Interestingly, no single regulator depletion caused significant cell shape change. However, perturbing two hits simultaneously, supervillin and myosin II, led to stress fiber disassembly and cell rounding. Overall, our systematic investigation shows that actin networks are robust to perturbations, and identifies regulatory modules controlling overall actin organization and resulting cell shape.