bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human thalamic recordings reveal that epileptic spikes block sleep spindle production during non-rapid eye movement sleep
Authors: Wodeyar Anirudh , Chinappen Dhinakaran , Mylonas Dimitris , Baxter Bryan , Manoach Dara S. , Eden Uri T. , Kramer Mark A. , Chu Catherine J. 
Published: April 2023

AbstractIn severe epileptic encephalopathies, epileptic activity contributes to progressive cognitive dysfunction. Several epileptic encephalopathies share the trait of spike-wave activation during non-rapid eye movement sleep (EE-SWAS), a state dominated by sleep oscillations known to coordinate offline memory consolidation. How epileptic activity impacts these thalamocortical sleep oscillations has not been directly observed in humans. Using a unique dataset of simultaneous human thalamic and cortical recordings in subjects with and without EE-SWAS, we reconcile prior conflicting observations about how epileptic spikes coordinate with sleep oscillations and provide direct evidence for epileptic spike interference of sleep spindle production. We find that slow oscillations facilitate both epileptic spikes and sleep spindles during stage 2 sleep (N2) at different phases of the slow oscillation. We show that sleep activated cortical epileptic spikes propagate to the thalamus (thalamic spike rate is increased after a cortical spike, p∼0). Thalamic spikes increase the spindle refractory period (p<1.5e-21). In patients with EE-SWAS, the abundance of thalamic spikes result in downregulation of spindles for 30 seconds after each thalamic spike (p=3.4e-11) and decreased overall spindle rate across N2 (p=2e-7). These direct human thalamocortical observations identify a novel mechanism through which epileptiform spikes could impact cognitive function, wherein sleep-activated epileptic spikes inhibit thalamic sleep spindles in epileptic encephalopathy.
Growth Hormone Accelerates Recovery From Acetaminophen-Induced Murine Liver Injury
Authors: Everton Elissa , Del Rio-Moreno Mercedes , Villacorta-Martin Carlos , Singh Bawa Pushpinder , Lindstrom-Vautrin Jonathan , Muramatsu Hiromi , Rizvi Fatima , Smith Anna R. , Tam Ying , Pardi Norbert , Kineman Rhonda , Waxman David J. , Gouon-Evans Valerie 
Published: April 2023

ABSTRACTBackground and AimsAcetaminophen (APAP) overdose is the leading cause of acute liver failure, with one available treatment, N-acetyl cysteine (NAC). Yet, NAC effectiveness diminishes about ten hours after APAP overdose, urging for therapeutic alternatives. This study addresses this need by deciphering a mechanism of sexual dimorphism in APAP-induced liver injury, and leveraging it to accelerate liver recovery via growth hormone (GH) treatment. GH secretory patterns, pulsatile in males and near-continuous in females, determine the sex bias in many liver metabolic functions. Here, we aim to establish GH as a novel therapy to treat APAP hepatotoxicity.Approach and ResultsOur results demonstrate sex-dependent APAP toxicity, with females showing reduced liver cell death and faster recovery than males. Single-cell RNA sequencing analyses reveal that female hepatocytes have significantly greater levels of GH receptor expression and GH pathway activation compared to males. In harnessing this female-specific advantage, we demonstrate that a single injection of recombinant human GH protein accelerates liver recovery, promotes survival in males following sub-lethal dose of APAP, and is superior to standard-of-care NAC. Alternatively, slow-release delivery of human GH via the safe nonintegrative lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP), a technology validated by widely used COVID-19 vaccines, rescues males from APAP-induced death that otherwise occurred in control mRNA-LNP-treated mice.ConclusionsOur study demonstrates a sexually dimorphic liver repair advantage in females following APAP overdose, leveraged by establishing GH as an alternative treatment, delivered either as recombinant protein or mRNA-LNP, to potentially prevent liver failure and liver transplant in APAP-overdosed patients.
Using rare genetic mutations to revisit structural brain asymmetry
Authors: Kopal Jakub , Kumar Kuldeep , Shafighi Kimia , Saltoun Karin , Modenato Claudia , Moreau Clara A. , Huguet Guillaume , Jean-Louis Martineau , Martin Charles-Olivier , Saci Zohra , Younis Nadine , Douard Elise , Jizi Khadije , Beauchamp-Chatel Alexis , Kushan Leila , Silva Ana I. , van den Bree Marianne B. M. , Linden David E. J. , Owen Michael J. , Hall Jeremy , Lippé Sarah , Draganski Bogdan , Sønderby Ida E. , Andreassen Ole A. , Glahn David C. , Thompson Paul M. , Bearden Carrie E. , Zatorre Robert , Jacquemont Sébastien , Bzdok Danilo 
Published: April 2023

AbstractAsymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.
Genome-resolved transcriptomics reveals novel organohalide-respiring bacteria from Aarhus Bay sediments
Authors: Zhang Chen , Bosma Tom N.P. , Atashgahi Siavash , Smidt Hauke 
Published: April 2023

AbstractOrganohalide-respiring bacteria (OHRB) are keystone microbes in bioremediation of sites contaminated with organohalides and in natural halogen cycling. Known OHRB belong to distinct genera within the phylaChloroflexota,ProteobacteriaandFirmicutes, whereas information about novel OHRB mediating natural halogen cycling remains scarce. In this study, we applied a genome-resolved transcriptomic approach to characterize the identity and activity of OHRB from PCE-respiring cultures previously enriched from sediments of Aarhus Bay. Combining short- and long-read sequencing approaches, we assembled 37 high quality bins with over 75 % completeness and less than 5 % contamination. Sixteen bins harbored RDase genes, and were affiliated taxonomically to the class ofBacilli, and phyla ofBacteroidota,Synergistota, andSpirochaetota, that have not been reported to catalyze reductive dehalogenation. Among the 16 bins, bin.26, phylogenetically closely related to the genusVulcanibacillus, contained an unprecedented 97 RDase genes. Of these, 84 RDase genes of bin.26 were transcribed during PCE dechlorination in addition to RDase genes from members ofSynergistales(bin.15 and bin.32) andBacteroidales(bin.18 and bin.24). Moreover, metatranscriptome analysis suggested the RDase genes were likely under the regulation of transcriptional regulators not previously associated with OHR, such as HrcA and SigW, which are known to respond to abiotic environmental stresses, such as temperature changes. Combined application of genomic methods enabled us to pinpoint novel OHRB from pristine environments not previously known to mediate reductive dechlorination and to provide evidence towards the diversity, activity and regulation of reductive dehalogenases.
5-ASA can functionally replace Clostridia to prevent a post-antibiotic bloom ofCandida albicansby maintaining epithelial hypoxia
Authors: Savage Hannah P. , Bays Derek J. , Gonzalez Mariela A. F. , Bejarano Eli. J. , Nguyen Henry , Masson Hugo L. P. , Carvalho Thaynara P. , Santos Renato L. , Thompson George R. , Bäumler Andreas J. 
Published: April 2023

ABSTRACTAntibiotic prophylaxis sets the stage for an intestinal bloom ofCandida albicans, which can progress to invasive candidiasis in patients with hematologic malignancies. Commensal bacteria can reestablish microbiota-mediated colonization resistance after completion of antibiotic therapy, but they cannot engraft during antibiotic prophylaxis. Here we use a mouse model to provide a proof of concept for an alternative approach, which replaces commensal bacteria functionally with drugs to restore colonization resistance againstC. albicans. Streptomycin treatment, which depletes Clostridia from the gut microbiota, disrupted colonization resistance againstC. albicansand increased epithelial oxygenation in the large intestine. Inoculating mice with a defined community of commensal Clostridia species reestablished colonization resistance and restored epithelial hypoxia. Notably, these functions of commensal Clostridia species could be replaced functionally with the drug 5-aminosalicylic acid (5-ASA), which activates mitochondrial oxygen consumption in the epithelium of the large intestine. When streptomycin-treated mice received 5-ASA, the drug reestablished colonization resistance againstC. albicansand restored physiological hypoxia in the epithelium of the large intestine. We conclude that 5-ASA treatment is a non-biotic intervention that restores colonization resistance againstC. albicanswithout requiring the administration of live bacteria.
Home security cameras as a tool for behavior observations and science affordability
Authors: Goolsby Billie C. , Fischer Marie-Therese , Chen Tony G. , Pareja-Mejía Daniela , Shaykevich Daniel A. , Lewis Amaris R. , Raboisson Gaelle , Lacey Madison P. , O’Connell Lauren A. 
Published: April 2023

AbstractReliably capturing transient animal behavior in the field and laboratory remains a logistical and financial challenge, especially for small ectotherms. Here, we present a camera system that is affordable, accessible, and suitable to monitor small, cold-blooded animals historically overlooked by commercial camera traps, such as small amphibians. The system is weather-resistant, can operate offline or online, and allows collection of time-sensitive behavioral data in laboratory and field conditions with continuous data storage for up to four weeks. The lightweight camera can also utilize phone notifications over Wi-Fi so that observers can be alerted when animals enter a space of interest, enabling sample collection at proper time periods. We present our findings, both technological and scientific, in an effort to elevate tools that enable researchers to maximize use of their research budgets. We discuss the relative affordability of our system for researchers in South America, home to the largest ectotherm diversity.
Variability in donor lung culture and relative humidity impact the stability of 2009 pandemic H1N1 influenza virus on nonporous surfaces
Authors: Qian Zhihong , Morris Dylan H. , Avery Annika , Kormuth Karen A. , Le Sage Valerie , Myerburg Michael M. , Lloyd-Smith James O. , Marr Linsey C. , Lakdawala Seema S. 
Published: April 2023

ABSTRACTRespiratory viruses can transmit by multiple modes, including contaminated surfaces, commonly referred to as fomites. Efficient fomite transmission requires that a virus remain infectious on a given surface material over a wide range of environmental conditions, including different relative humidities. Prior work examining the stability of influenza viruses on surfaces has relied upon virus grown in media or eggs, which does not mimic the composition of virus-containing droplets expelled from the human respiratory tract. In this study, we examined the stability of the 2009 pandemic H1N1 (H1N1pdm09) virus on a variety of nonporous surface materials at four different humidity conditions. Importantly, we used virus grown in primary human bronchial epithelial (HBE) cultures from different donors to recapitulate the physiological microenvironment of expelled viruses. We observed rapid inactivation of H1N1pdm09 on copper under all experimental conditions. In contrast to copper, viruses were stable on polystyrene plastic, stainless steel, aluminum, and glass, at multiple relative humidity conditions, but greater decay on ABS plastic was observed at short time points. However, the half-lives of viruses at 23% relative humidity were similar among non-copper surfaces and ranged from 4.5 to 5.9 hours. Assessment of H1N1pdm09 longevity on nonporous surfaces revealed that virus persistence was governed more by differences among HBE culture donors than by surface material. Our findings highlight the potential role of an individual’s respiratory fluid on viral persistence and could help explain heterogeneity in transmission dynamics.IMPORTANCESeasonal epidemics and sporadic pandemics of influenza cause a large public health burden. Although influenza viruses disseminate through the environment in respiratory secretions expelled from infected individuals, they can also be transmitted by contaminated surfaces where virus-laden expulsions can deposit. Understanding virus stability on surfaces within the indoor environment is critical to assessing influenza transmission risk. We found that influenza virus stability is affected by the host respiratory secretion in which the virus is expelled, the surface material on which the droplet lands, and the ambient relative humidity of the environment. Influenza viruses can remain infectious on many common surfaces for prolonged periods, with half-lives of 4.5-5.9 hours. These data imply that influenza viruses are highly persistent in indoor environments in biologically-relevant matrices. Decontamination and engineering controls should be used to mitigate influenza virus transmission.
Fluid-Structure Interactions of Peripheral Arteries Using a Coupledin silicoandin vitroApproach
Authors: Schoenborn S. , Lorenz T. , Kuo K. , Fletcher D.F. , Woodruff M. A. , Pirola S. , Allenby M. C. 
Published: April 2023

AbstractVascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance, such as during plaque development or after bypass grafting and stenting, cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupledsilico-vitroplatform which allows for the validation of numerical fluid-structure interaction (FSI) results as a numerical model and physical prototype. This numerical one-way and two-way FSI study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms. Phantoms within a compliance range of 1.4 - 68.0%/100mmHg were fabricatedviaadditive manufacturing and silicone casting, then mechanically characterisedviaring tensile testing and optical analysis under direct pressurisation with differences in measured compliance ranging between 10 - 20% for the two methods. One-way FSI coupling underestimated arterial wall compliance by up to 14.71% compared to two-way FSI modelling. Overall, Smooth-On Solaris matched the compliance range of the numerical andin vivopatient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.
Mining for a New Class of Fungal Natural Products: The Evolution, Diversity, and Distribution of Isocyanide Synthase Biosynthetic Gene Clusters
Authors: Nickles Grant R. , Oestereicher Brandon , Keller Nancy P. , Drott Milton T. 
Published: April 2023

ABSTRACTThe products of non-canonical isocyanide synthase (ICS) biosynthetic gene clusters (BGCs) have notable bioactivities that mediate pathogenesis, microbial competition, and metal-homeostasis through metal-associated chemistry. We sought to enable research into this class of compounds by characterizing the biosynthetic potential and evolutionary history of these BGCs across the Fungal Kingdom. We developed the first genome-mining pipeline to identify ICS BGCs, locating 3,800 ICS BGCs in 3,300 genomes. Genes in these clusters share promoter motifs and are maintained in contiguous groupings by natural selection. ICS BGCs are not evenly distributed across fungi, with evidence of gene-family expansions in several Ascomycete families. We show that the ICSdit1/2gene cluster family (GCF), which was thought to only exist in yeast, is present in ∼30% of all Ascomycetes, including many filamentous fungi. The evolutionary history of theditGCF is marked by deep divergences and phylogenetic incompatibilities that raise questions about convergent evolution and suggest selection or horizontal gene transfers have shaped the evolution of this cluster in some yeast and dimorphic fungi. Our results create a roadmap for future research into ICS BGCs. We developed a website (www.isocyanides.fungi.wisc.edu) that facilitates the exploration, filtering, and downloading of all identified fungal ICS BGCs and GCFs.
Identification of the glycosylphosphatidylinositol-specific phospholipase A2 (GPI-PLA2) of GPI fatty acid remodelling inTrypanosoma brucei
Authors: Ji Zhe , Nagar Rupa , Duncan Samuel M. , Sampaio Guther Maria Lucia , Ferguson Michael A.J. 
Published: April 2023

AbstractThe biosynthesis of glycosylphosphatidylinositol (GPI) anchored proteins (GPI-APs) in the parasitic protozoanTrypanosoma bruceiinvolves fatty acid remodelling of the GPI precursor molecules before they are transferred to protein in the endoplasmic reticulum. The genes encoding the requisite phospholipase A2 and A1 activities for this remodelling have thus far been elusive. Here, we identify a gene, Tb927.7.6110, that encodes a protein that is necessary and sufficient for GPI-phospholipase A2 (GPI-PLA2) activity in the procyclic form of the parasite. The predicted protein product belongs to the alkaline ceramidase, PAQR receptor, Per1, SID-1, and TMEM8 (CREST) superfamily of transmembrane hydrolase proteins and shows sequence similarity to Post-GPI-Attachment to Protein 6 (PGAP6), a GPI-PLA2 that acts after transfer of GPI precursors to protein in mammalian cells. The trypanosome Tb927.7.6110 GPI-PLA2 gene resides in a locus with two closely related genes Tb927.7.6150 and Tb927.7.6170, one of which (Tb927.7.6150) most likely encodes a catalytically inactive protein. The absence of GPI-PLA2 in the null mutant procyclic cells not only affected fatty acid remodelling but also reduced GPI anchor sidechain size on mature GPI-anchored procyclin glycoproteins. This reduction in GPI anchor sidechain size was reversed upon the add back of Tb927.7.6110 and of Tb927.7.6170, despite the latter not encoding GPI precursor GPI-PLA2 activity.
Recent evolution of flowering time across multiple European plant species correlates with changes in aridity
Authors: Rauschkolb Robert , Durka Walter , Godefroid Sandrine , Dixon Lara , Bossdorf Oliver , Ensslin Andreas , Scheepens J.F. 
Published: April 2023

AbstractOngoing global warming and increasing drought frequencies impact plant populations and potentially drive rapid evolutionary adaptations. Historical comparisons, where plants grown from seeds collected in the past are compared to plants grown from freshly collected seeds from populations of the same sites, are a powerful method to investigate recent evolutionary changes across many taxa. We used 21-38 year-old seeds of 13 European plant species, stored in seed banks and originating from Mediterranean and temperate regions, together with recently collected seeds from the same sites for a greenhouse experiment to investigate shifts in flowering phenology as a potential result of adaptive evolution to changes in drought intensities over the last decades. We further used single nucleotide polymorphism (SNP) markers to quantify relatedness and levels of genetic variation. We found that, across species, current populations grew faster and advanced their flowering. These shifts were correlated with changes in aridity at the population origins, suggesting that increased drought induced evolution of earlier flowering, whereas decreased drought lead to weak or inverse shifts in flowering phenology. In five out of the 13 species, however, the SNP markers detected strong differences in genetic variation and relatedness between the past and current populations collected, indicating that other evolutionary processes may have contributed to changes in phenotypes. Our results suggest that changes in aridity may have influenced the evolutionary trajectories of many plant species in different regions of Europe, and that flowering phenology may be one of the key traits that is rapidly evolving.Highlighted student paperWe demonstrated that accurately sampled and stored seed collections from conventional seed banks can, with some limitations, be used in a similar way as the increasingly popular resurrection approach sensu stricto. Given the vast availability of seeds stored in seed banks, this opens up a large potential for future research on rapid evolutionary adaptation to changing environmental conditions across a wide variety of taxa suitable for resurrection. Furthermore, this work is unique and novel, as we combine greenhouse experiments with molecular and climatic data to disentangle potential drivers for the observed phenotypic evolution, which, to our knowledge, was never done in resurrection studies.
Level of sub-contracting design responsibilities in design and construct civil engineering bridge projects
Authors: de Graaf Robin , Pater Rens , Voordijk Hans 
Published: April 2023

PurposeIn the construction industry, an under researched area of study is how main contractor (MC) sub-contract design responsibilities to sub-contractor (SC). This lack of knowledge is particularly serious in the context of delivery methods such as design and construct where design responsibilities are pushed down the supply chain. In this study, it is aimed to explore which level of design responsibility MCs sub-contract to SCs, for what reasons, and what the impact of sub-contracting decisions is on projects.Design/methodology/approachA qualitative in-depth multiple case study was conducted. Six sub-contracting cases were examined in two civil engineering projects. In each project, the MCs sub-contracted pre-fabricated beams, reinforcement and railing to SCs. Data collection included document analysis and interviews. A within-case and cross-case analysis was conducted to examine emerging empirical patterns. These patterns were used to elaborate theory and develop propositions.FindingsMCs sub-contracted design responsibilities to SCs as suggested by literature. However, despite that sub-contracting was in keeping with literature, several problems were reported in the cases where MCs involved SCs no earlier than in the construction stage. This is not to be expected according to theory.Originality/valueThis study adds value to the sub-contracting field as it provides new insights in relationships between the level of design responsibilities sub-contracted and the impact of that on projects. The study also revealed new factors such as building information modelling (BIM) interoperability that should get more attention in sub-contracting.