bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psilocybin induces acute and persisting alterations in immune status and the stress response in healthy volunteers
Authors: Mason N.L. , Szabo A. , Kuypers K.P.C. , Mallaroni P.A. , de la Torre Fornell R. , Reckweg J.T. , Tse D.H.Y. , Hutten N.R.P.W. , Feilding A. , Ramaekers J.G. 
Published: November 2022

AbstractPatients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on immune functioning, HPA axis activity in response to stress, and associated psychological outcomes is preliminary. To address this, we conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n=30) or 0.17 mg/kg psilocybin (n=30). Blood samples were taken to assess acute changes in immune status, and 7 days after drug administration. Seven days’ post-administration, participants in each treatment group were further subdivided: 15 underwent a stress induction protocol, and 15 underwent a control protocol. Ultra-high field magnetic resonance spectroscopy was used to assess whether acute changes in glutamate or glial activity were associated with changes in immune functioning. Finally, questionnaires assessed persisting self-report changes in mood and social behavior. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin (IL)-1α, IL-1β, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-α concentrations returned to baseline, while IL-6 and CRP concentrations were persistently reduced in the psilocybin group. Changes in the immune profile were related to acute neurometabolic activity as acute reductions in TNF-α were linked to lower concentrations of glutamate in the hippocampus. Additionally, the more of a reduction in IL-6 and CRP seven days after psilocybin, the more persisting positive mood and social effects participants reported. Regarding the stress response, after a psychosocial stressor, psilocybin blunted the cortisol response compared to placebo. Such acute and persisting changes may contribute to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.
Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes
Authors: Grewal Ramandip , Nguyen Lena , Buchan Sarah A , Wilson Sarah E , Nasreen Sharifa , Austin Peter C. , Brown Kevin A. , Fell Deshayne B. , Gubbay Jonathan , Schwartz Kevin L. , Tadrous Mina , Wilson Kumanan , Kwong Jeffrey C 
Published: November 2022

ABSTRACTBackgroundTo inform planning for further booster doses of COVID-19 vaccines, we estimated the effectiveness of monovalent mRNA vaccines against Omicron-associated severe outcomes in adults over time.MethodsWe used a test-negative design and multivariable logistic regression to estimate vaccine effectiveness (VE; 2, 3, or 4 doses compared to unvaccinated individuals) and marginal effectiveness (3 or 4 doses compared to 2 doses) against Omicron-associated hospitalization or death among community-dwelling adults aged ≥50 years who were tested for SARS-CoV-2 between January 2, 2022 and October 1, 2022 in Ontario, Canada, stratified by age group and time since vaccination. We also compared VE during periods of Omicron BA.1/BA.2 and BA.4/BA.5 sublineage predominance.ResultsWe included 11,160 cases of Omicron-associated severe outcomes and 62,880 test-negative symptomatic controls. Depending on the age group, compared to unvaccinated individuals, VE was 91-98% 7-59 days after a third dose, waned to 76-87% after ≥240 days, was restored to 92-97% 7-59 days after a fourth dose, and waned to 86-89% after ≥120 days. Trends in marginal effectiveness were consistent with VE estimates. VE was lower during the BA.4/BA.5-predominant period compared to the BA.1/BA.2-predominant period based on the same intervals since vaccination.ConclusionOur findings suggest that 1 or 2 booster doses of monovalent mRNA COVID-19 vaccines initially restored very strong protection against Omicron-associated severe outcomes in all age groups, but VE subsequently declined over time with some age-related differences, and particularly so during a period of BA.4/BA.5 predominance.
Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy
Authors: Royer Jessica , Larivière Sara , Rodriguez-Cruces Raul , Cabalo Donna Gift , Tavakol Shahin , Auer Hans , Park Bo-yong , Paquola Casey , Smallwood Jonathan , Jefferies Elizabeth , Caciagli Lorenzo , Bernasconi Andrea , Bernasconi Neda , Frauscher Birgit , Bernhardt Boris C. 
Published: November 2022

AbstractTemporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a contracted gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independentpost mortemdataset, we observed thatin vivofindings reflected topographical variations in cortical lamination patterns, confirming that TLE-related changes in the microstructural gradient reflected increased proximity of regions with more dissimilar laminar structure. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm, and correlated with inter-individual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a parsimonious explanation for functional network reorganization and cognitive dysfunction characteristic of TLE.
A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenicEscherichia coliinfections in mice
Authors: Williams Asher J. , Warfel Katherine F. , Desai Primit , Li Jie , Lee Jen-Jie , Wong Derek A. , Sobol Sarah E. , Jewett Michael C. , Chang Yung-Fu , DeLisa Matthew P. 
Published: November 2022

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) is the primary etiologic agent of traveler’s diarrhea and a major cause of diarrheal disease and death worldwide, especially in infants and young children. Despite significant efforts over the past several decades, an affordable vaccine that significantly reduces mortality and morbidity associated with moderate to severe diarrhea among children under the age of 5 years remains an unmet aspirational goal. Here, we describe robust, cost-effective biosynthetic routes that leverage glycoengineered strains of non-pathogenicEscherichia colior their cell-free extracts for producing conjugate vaccine candidates against two of the most prevalent O serogroups of ETEC, O148 and O78. Specifically, we demonstrate site-specific installation of O-antigen polysaccharides (O-PS) corresponding to these serogroups onto licensed carrier proteins using the oligosaccharyltransferase PglB fromCampylobacter jejuni. The resulting conjugates stimulate strong O-PS-specific humoral responses in mice and elicit IgG antibodies that possess bactericidal activity against the cognate pathogens. We also show that one of the prototype conjugates decorated with serogroup O148 O-PS confers protection against ETEC infection in mice. We anticipate that our bacterial cell-based and cell-free platforms will enable creation of multivalent formulations with the potential for broad ETEC serogroup protection and increased access through low-cost biomanufacturing.
A fluorescent reporter for FtsA is functional as the sole FtsA inEscherichia coliand has hypermorphic properties
Authors: Cameron Todd A. , Margolin William 
Published: November 2022

AbstractFtsA, a homolog of actin, is essential for cell division ofEscherichia coliand is widely conserved among many bacteria. FtsA helps to tether polymers of the bacterial tubulin homolog FtsZ to the cytoplasmic membrane as part of the cytokinetic Z ring. GFP fusions to FtsA have illuminated FtsA’s localization in liveE. coli, but these fusions have not been fully functional and required the presence of the native FtsA. Here, we characterize “sandwich” fusions ofE. coliFtsA to either mCherry or msfGFP that are fully functional for cell division and exhibit fluorescent rings at midcell that persist throughout constriction until cell separation. FtsA within the Z ring moved circumferentially like FtsZ, and FtsA outside the rings formed highly dynamic patches at the membrane. Notably, both FtsA-mCherry and FtsA-msfGFP acted as mild hypermorphs, as they were not toxic when overproduced, bypassed the essential cell division protein ZipA, and suppressed several thermosensitiveftsalleles, although not as effectively as the prototypical hypermorph FtsA*. Overall, our results indicate that fluorescent FtsA sandwich fusions can be used as the sole FtsA inE. coliand thus should shed new light on FtsA dynamics during the cell division cycle in this model system.ImportanceFtsA is a key conserved cell division protein, andE. coliis the most well studied model system for bacterial cell division. One obstacle to full understanding of this process is the lack of a fully functional fluorescent reporter for FtsAin vivo. Here, we describe a fluorescent fusion toE. coliFtsA that divides cells efficiently in the absence of the native FtsA and can be used to monitor FtsA dynamics during cell division.
Prevalence and pattern of adverse events following COVID 19 vaccination among adult population in Sokoto metropolis, northwest, Nigeria
Authors: Adamu Habibullah , Lawal Sufyanu , Bawa Ishaka Alhaji , Sani Akilu Muhammad , Adamu Adamu Ahmed 
Published: November 2022

AbstractBackgroundCOVID-19 still poses a major public health challenge worldwide and vaccination remains one of the major interventions to control the disease. Different types of vaccines approved by the World Health Organization (WHO) are currently in use across the world to protect against the disease. As all vaccines are associated with some adverse reactions (ARs), this study assessed the prevalence and pattern of adverse events following immunization (AEFI) after receiving COVID-19 vaccine among the adult population in Sokoto metropolis, North-west, NigeriaMethodsWe conducted a cross-sectional study among 230 adults in Sokoto metropolis who received COVID-19 vaccine. Data was collected using a structured questionnaire administered via personal phone calls to respondents who were selected via a systematic sampling technique. For data analysis, IBM SPSS version 25.0 was used.ResultsThe Majority of the participants [183 (79.7%)] experienced AEFI. The most common adverse events were body weakness [157(85%)], fever [111(60.3%)] and headache [103(56%)]. Up to half of the respondents that experienced AEFI said it occurred within minutes and a few hours, whereas 75 (40.8%) said it was within 2-3 days. Up to 66.3 of the adverse reactions were mild and lasted between a few hours (37.5%) and one day (31.5%); however, 15.2% of the respondents had severe reactions of which 22.7% were admitted to a health facility. The development of AEFI was linked to the absence of an underlying medical condition, a previous history of AEFI, and a history of drug reaction.ConclusionThe majority of respondents reported adverse events following COVID-19 vaccination, with body weakness, fever, and headache being the most common AEFIs. The underlying medical condition as well as a history of adverse drug reactions were predictors of the development of adverse reactions following COVID-19 vaccination. Service providers at each COVID-19 vaccination point should always take the time to explain to vaccine recipients that adverse reactions are possible; however, they should reassure them that most ARs resolve within a few hours to a few days.
Gasdermin-E mediates mitochondrial damage in axons and neurodegeneration
Authors: Neel Dylan V , Basu Himanish , Gunner Georgia , Bergstresser Matthew D , Giadone Richard M. , Chung Haeji , Miao Rui , Chou Vicky , Brody Eliza M. , Jiang Xin , Lee Edward B. , Marques Christine , Held Aaron , Wainger Brian , Lagier-Tourenne Clotilde , Zhang Yong-Jie , Petrucelli Leonard , Young-Pearse Tracy L. , Chen-Plotkin Alice S , Rubin Lee L. , Lieberman Judy , Chiu Isaac M 
Published: November 2022

SummaryMitochondrial dysfunction and axon loss are hallmarks of neurologic diseases. Gasdermin (GSDM) proteins are executioner pore-forming molecules that mediate cell death, yet their roles in the central nervous system (CNS) are not well understood. Here, we find that one GSDM family member, GSDME is expressed by both mouse and human neurons. GSDME plays a role in mitochondrial damage and axon loss. Mitochondrial neurotoxins induced caspase-dependent GSDME cleavage and rapid localization to mitochondria in axons, where GSDME promoted mitochondrial depolarization, trafficking defects, and neurite retraction. The frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS)-associated proteins TDP-43 and PR-50 induced GSDME-mediated damage to mitochondria and neurite loss. GSDME deficiency prolonged survival, ameliorated motor dysfunction, and rescued motor neuron loss in the SOD1G93Amouse model of ALS. GSDME knockdown also protected against neurite loss in ALS patient iPSC-derived motor neurons. Thus, we identify GSDME as an executioner of neuronal mitochondrial dysfunction that contributes to neurodegeneration.Graphical AbstractHighlightsGSDME is expressed by neurons and activated by mitochondrial neurotoxinsActivated GSDME drives axonal mitochondrial damage and neurite loss prior to cell deathALS/FTD associated TDP-43 and PR-50 induces GSDME-driven neurite loss in mouse and human iPSC-derived neurons.SOD1G93Amice show ameliorated disease progression and motor neuron loss in absence of GSDME
Invasive ant learning is not affected by seven potential neuroactive chemicals
Authors: Galante Henrique , Czaczkes Tomer J. 
Published: November 2022

AbstractNectar-feeding insects are often the victims of psychoactive manipulation, with plants lacing their nectar with secondary metabolites such as alkaloids and non-protein amino acids which often boost learning, foraging, or recruitment. However, the effect of neuroactive chemicals has seldomly been explored in ants. Argentine ants (Linepithema humile) are one of the most damaging invasive alien species worldwide. Enhancing or disrupting cognitive abilities, such as learning, has the potential to improve management efforts, for example by increasing preference for a bait, or improving ants’ ability to learn its characteristics or location. Here, we test the effects of seven potential neuroactive chemicals - two alkaloids: caffeine and nicotine; two biogenic amines: dopamine and octopamine, and three non-protein amino acids: β-alanine, GABA and taurine - on the cognitive abilities of invasiveL. humileusing bifurcation mazes. Our results confirm that these ants are strong associative learners, requiring as little as one experience to develop an association. However, we show no short-term effect of any of the chemicals tested on spatial learning, and in addition no effect of caffeine on short-term olfactory learning. This lack of effect is surprising, given the extensive reports of the tested chemicals affecting learning and foraging in bees. This mismatch could be due to the heavy bias towards bees in the literature, a positive result publication bias, or differences in methodology.Graphical Abstract
OpenFIBSEM: an application programming interface for easy FIB/SEM automation
Authors: Cleeve Patrick , Dierickx David , Buckley Genevieve , Gorelick Sergey , Naegele Lucile , Burne Lachlan , Whisstock James C , de Marco Alex 
Published: November 2022

AbstractAutomation in microscopy is the key to success in long and complex experiments. Most microscopy manufacturers provide Application Programming Interfaces (API) to enable communication between a user-defined program and the hardware. Although APIs effectively allow the development of complex routines involving hardware control, the developers need to build the applications from basic commands. Here we present a Software Development Kit (SDK) for easy control of Focussed Ion Beam Scanning Electron Microscopes (FIB/SEM) microscopes. The SDK, which we named OpenFIBSEM consists of a suite of building blocks for easy control that simplify the development of complex automated workflows.
Inactivation mechanisms of Influenza A virus under pH conditions encountered in aerosol particles as revealed by whole-virus HDX-MS
Authors: David Shannon C. , Vadas Oscar , Glas Irina , Schaub Aline , Luo Beiping , D’Angelo Giovanni , Montoya Jonathan Paz , Bluvshtein Nir , Hugentobler Walter , Klein Liviana K. , Motos Ghislain , Pohl Marie , Violaki Kalliopi , Nenes Athanasios , Krieger Ulrich K. , Stertz Silke , Peter Thomas , Kohn Tamar 
Published: November 2022

ABSTRACTMultiple respiratory viruses including Influenza A virus (IAV) can be transmitted via expiratory aerosol particles, and aerosol pH was recently identified as a major factor influencing airborne virus infectivity. For indoor air, small exhaled aerosols undergo rapid acidification to pH ∼4. IAV is known to be sensitive to mildly acidic conditions encountered within host endosomes, however, it is unknown whether the same mechanisms could mediate viral inactivation within the more acidic aerosol micro-environment. Here, we identified that transient exposure to pH 4 caused IAV inactivation by a two-stage process, with an initial sharp decline in infectious titers that was mainly attributed to premature attainment of the post-fusion conformation of viral protein haemagglutinin (HA). Changes to HA were observed by hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) as early as 10 seconds post-exposure to acidic conditions. In addition, virion integrity was partially but irreversibly affected by acidic conditions. This was attributed to a progressive unfolding of the internal matrix protein 1 (M1), and aligned with a more gradual decline in viral infectivity with time. In contrast, no acid-mediated changes to the genome or lipid envelope were detected. Our HDX-MS data are in agreement with other more labor-intensive structural analysis techniques such as X-ray crystallography, highlighting the usefulness of whole-virus HDX-MS for multiplexed protein analyses, even within enveloped viruses such as IAV. Improved understanding of respiratory virus fate within exhaled aerosols constitutes a global public health priority, and information gained here could aid development of novel strategies to control the airborne persistence of seasonal and/or pandemic influenza in the future.
Transport and utilization of glycogen breakdown products byGardnerellaspp. from the human vaginal microbiome
Authors: Bhandari Pashupati , Hill Janet E. 
Published: November 2022

AbstractMultipleGardnerellaspecies frequently co-occur in vaginal microbiomes, and several factors including competition for nutrients such as glycogen could determine their population structure. AlthoughGardnerellaspp. can hydrolyze glycogen to produce glucose, maltose, maltotriose and maltotetraose, how these sugars are transported and utilized for growth is unknown. We determined the distribution of genes encoding transporter proteins associated with the uptake of glucose, maltose, and malto-oligosaccharides and maltodextrins amongGardnerellaspecies. A total of five different ABC transporters were identified inGardnerellaspp. of which MusEFGK2I and MalXFGK were conserved across all 15Gardnerellaisolates. RafEFGK and TMSP (trehalose, maltose, sucrose and palatinose) operons were specific toG. vaginaliswhile the MalEFG transporter was identified inG. leopoldiionly. Although no glucose specific sugar-symporters were identified, putative ‘glucose/galactose porters’ and components of a phosphotransferase system were identified. In laboratory experiments, allGardnerellaisolates grew more in the presence of glucose, maltose, maltotriose and maltotetraose compared to un-supplemented media. In addition, most isolates (10/15) showed significantly more growth on maltotetraose compared to glucose (Kruskal Wallis, P < 0.05) suggesting their preference for longer chain malto-oligosaccharides. Our findings show that although putative MusEFGK2I and MalXFGK transporters are found in allGardnerellaspp., some species-specific transporters are also present. Observed distribution of genes encoding transporter systems was consistent with laboratory observations thatGardnerellaspp. grow better on longer chain malto-oligosaccharides.ImportanceIncreased abundance ofGardnerellaspp. is a diagnostic characteristic of bacterial vaginosis, an imbalance in the human vaginal microbiome associated with troubling symptoms and negative reproductive health outcomes, including increased transmission of sexually transmitted infections and preterm birth. Competition for nutrients is likely an important factor in causing dramatic shifts in the vaginal microbial community.Gardnerellaproduces enzymes to digest glycogen, an important nutrient source for vaginal bacteria, but little is known about the mechanisms inGardnerellafor uptake of the products of this digestion, or whetherGardnerellause some or all of the products. Our results indicate thatGardnerellamay have evolved to preferentially use a subset of the glycogen breakdown products, which would help them reduce direct competition with some other bacteria in the vagina.