bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ClpX chaperone and a hypermorphic FtsA variant with impaired self-interaction are mutually compensatory for coordinatingStaphylococcus aureuscell division
Authors: Henriksen Camilla , Bæk Kristoffer T. , Wacnik Katarzyna , Gallay Clement , Veening Jan-Willem , Foster Simon J. , Frees Dorte 
Published: August 2023

AbstractBacterial cell division requires the coordinated assembly and disassembly of a large protein complex called the divisome, however, the exact role of molecular chaperones in this critical process remains unclear. In the important pathogenic bacteriumStaphylococcus aureus, the ClpX chaperone is essential for growth at 30°C and microscopic analyses suggested that ClpX plays a temperature-dependent role in cell division. We here provide genetic evidence that ClpX unfoldase activity is a determinant for proper coordination of cell division by showing that a spontaneous G325V substitution in the ATP-binding domain of the essential FtsA cell division protein rescues growth and septum synthesis in aStaphylococcus aureus clpXmutant. The polymerization state of FtsA is thought to control initiation of bacterial septum synthesis and, while restoring the aberrant FtsA dynamics inclpXcells, the FtsAG325Vvariant displayed reduced ability to interact with itself and other cell division proteins. In wild-type cells, theftsAG325Vallele shared phenotypes withE. colisuperfissionftsAmutants and accelerated the cell cycle, increased the risk of daughter cell lysis, and conferred sensitivity to heat and antibiotics inhibiting cell wall synthesis. Strikingly, lethality was mitigated by spontaneous mutations that inactivate ClpX. Taken together, our results suggest that ClpX promotes septum synthesis by antagonizing FtsA interactions and illuminates the critical role of a protein unfoldase in coordinating bacterial cell division.IMPORTANCEEssential biological processes, such as cell division, are performed by multiple proteins working together in dynamic functional complexes. In eukaryotic cells, the disassembly of such molecular machines is often assisted by molecular chaperones capable of unfolding proteins. The ClpX unfoldase is conserved from bacteria to humans, however, the roles of ClpX in bacterial cell biology remain relatively unexplored. By combining genetic methods with super-resolution microscopy techniques, we show here that ClpX and a mutant variant of the essential cell division protein FtsA mutually compensate for each other in controlling cell division of the pathogenic bacteriumStaphylococcus aureus.The selected FtsAG325Vvariant has diminished self-interactions and restored the aberrant FtsA dynamics inclpXcells suggesting that ClpX promotes cell division by antagonizing FtsA protein interactions. This study, for the first time, illuminates the important role of protein unfoldases in the functioning of the divisome, a multienzyme complex fundamental to bacterial reproduction.
Pediatric and Adult Patients with ME/CFS following COVID-19: A Structured Approach to Diagnosis Using the Munich Berlin Symptom Questionnaire (MBSQ)
Authors: Peo Laura C. , Wiehler Katharina , Paulick Johannes , Gerrer Katrin , Leone Ariane , Viereck Anja , Haegele Matthias , Stojanov Silvia , Warlitz Cordula , Augustin Silvia , Alberer Martin , Hattesohl Daniel B. R. , Froehlich Laura , Scheibenbogen Carmen , Mihatsch Lorenz , Pricoco Rafael , Behrends Uta 
Published: August 2023

ABSTRACTPurposeA subset of patients with post-COVID-19 condition (PCC) fulfill the clinical criteria of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). To establish the diagnosis of ME/CFS for clinical and research purposes, comprehensive scores have to be evaluated.MethodsWe developed the Munich Berlin Symptom Questionnaires (MBSQs) and supplementary scoring sheets (SSSs) to allow for a rapid evaluation of common ME/CFS case definitions. The MBSQs were applied to young patients with chronic fatigue and post-exertional malaise (PEM) who presented to the MRI Chronic Fatigue Center for Young People (MCFC). Trials were retrospectively registered (NCT05778006,NCT05638724).ResultsUsing the MBSQs and SSSs, we report on ten patients aged 11 to 25 years diagnosed with ME/CFS after asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19. Results from their MBSQs and from well-established patient-reported outcome measures indicated severe impairments of daily activities and health-related quality of life.ConclusionsME/CFS can follow SARS-CoV-2 infection in patients younger than 18 years, rendering structured diagnostic approaches most relevant for pediatric PCC clinics. The MBSQs and SSSs represent novel diagnostic tools that can facilitate the diagnosis of ME/CFS in children, adolescents, and adults with PCC and other post-viral syndromes.What is knownME/CFS is a frequent debilitating illness. For diagnosis, an extensive differential diagnostic workup is required and the evaluation of clinical ME/CFS criteria. ME/CFS following COVID-19 has been reported in adults but not in pediatric patients younger than 19 years of age.What is newWe present novel questionnairs (MBSQs), as tools to assess common ME/CFS case definitions in pediatric and adult patients with post-COVID-19 condition and beyond. We report on ten patients aged 11 to 25 years diagnosed with ME/CFS following asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19.
TFF1 – a new Biomarker in Liquid Biopsies of Retinoblastoma under Therapy
Authors: Busch Maike Anna , Haase André , Alefeld Emily , Biewald Eva , Jabbarli Leyla , Dünker Nicole 
Published: August 2023

AbstractEffective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1 secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC therapy responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients’ blood serum displayed low to undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared to blood serum AH represents the more reliable source for TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimal invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens.Simple SummaryEffective management of retinoblastoma (RB), a common childhood eye cancer, requires accurate diagnosis and monitoring during therapy. In this study the liquid biopsy marker potential of the secreted trefoil family factor peptide 1 (TFF1), described as a biomarker of a more advanced RB subtype, was explored. TFF1 expression levels were investigated in aqueous humor (AH) of RB patients after enucleation and in RB patients undergoing intravitreal chemotherapy and compared with TFF1 expression levels in RB patients’ blood serum. AH showed consistent TFF1 levels in a subgroup of RB patients, remarkably decreasing post-therapy in responsive patients. Blood serum of RB patients only displayed low to non-detectable and therapy-independent TFF1 levels. The study suggests TFF1 expression in AH as a reliable biomarker, aiding RB diagnosis and treatment assessment and highlights it’s potential for non-invasive RB therapy monitoring.
Reference ranges for cardiovascular function during exercise: effects of aging and gender on performance
Authors: Schweitzer Ronny , de Marvao Antonio , Shah Mit , Inglese Paolo , Kellman Peter , Berry Alaine , Statton Ben , O’Regan Declan P 
Published: August 2023

AbstractPurposeReal-time (RT) exercise cardiac magnetic resonance imaging (exCMR) provides a highly reproducible and accurate assessment of cardiac volumes during maximal exercise. It has advantages over alternative approaches due to its high spatial resolution and use of physiological stress. Here we define the healthy response to exercise in adults and the effects of age and gender on performance.Materials and MethodsBetween 2018 and 2021, we conducted CMR evaluation on 169 healthy adults who had no known cardiovascular disease, did not harbour genetic variants associated with cardiomyopathy, and who completed an exCMR protocol using a pedal ergometer. Participants were imaged at rest and after exercise with left ventricular parameters measured using commercial software by two readers. Eight participants were excluded from the final analysis due to poor image quality and/or technical issues. Prediction intervals were calculated for each parameter.ResultsExercise caused an increase in heart rate (64±9 bpm vs 133±19 bpm,P< 0.001), left ventricular end-diastolic volume (140±32 ml vs 148±35 ml,P< 0.001), stroke volume (82±18 ml vs 102±25 ml,P< 0.001), ejection fraction (59±6% vs 69±7%,P< 0.001), and cardiac output (5.2±1.1 l/min vs 13.5±3.9 l/min,P< 0.001), with a decrease in left ventricular end-systolic volume (58±18 ml vs 46±15 ml,P< 0.001). There was an effect of gender and age on response to exercise across most parameters. Measurements showed good to excellent intra- and inter-observer agreement.ConclusionIn healthy adults, an increase in cardiac output after exercise is driven by a rise in heart rate with both increased ventricular filling and emptying. We establish normal ranges for exercise response, stratified by age and gender, as a reference for the use of exCMR in clinical practice.
Circulating ADAM17 is associated with COVID-19 severity
Authors: Pan Mengyu , Goncalves Isabel , Edsfeldt Andreas , Sun Jiangming , Swärd Per 
Published: August 2023

AbstractBackgroundADAM17 are emerging as an important role in the severe outcomes of COVID-19. This study aims to characterize causal relationship between ADAM17 and COVID-19.MethodsUsing mendelian randomization analyses, we examined the causal effects for circulating ADAM17 on COVID-19 outcomes using summary statistics from large genome wide association studies of ADAM17 (up to 35 559 individuals) from the Icelandic Cancer Project and deCODE genetics, critical COVID-19 (cases:13 769; controls:1 072 442), hospitalized COVID-19 (cases:32 519; controls: 2 062 805) and SARS-CoV-2 infection (cases:122 616; controls:2 475 240) from the COVID-19 Host Genetics Initiative.ResultsMendelian randomization analyses demonstrated that 1 standard deviation increase of genetically determined circulating ADAM17 at extracellular domain were associated with increasing risk of developing critical COVID-19 (odds ratio [OR]=1.26, 95% CI 1.03-1.55). Multivariable MR analysis suggested a direct causal role of circulating ADAM17 at extracellular domain on the risk of critical COVID-19 (OR=1.09; 95% CI 1.01-1.17), accounting for body mass index. Casual effects for the cytoplasmic domain of ADAM17 on COVID-19 were not observed.ConclusionOur results suggest that the increased circulating ADAM17 at extracellular domain are associated with a high risk of critical COVID-19 strengthening that of ADAM17 may contribute to the risk stratification and a therapeutic option for severe COVID-19.What is already known on this topicVarious inflammatory stimuli, as well as the SARS-CoV-2 S-protein, elevate the activity of a disintegrin and metalloproteinase 17 (ADAM17). Inhibition of ADAM17 activityin vitrohas illustrated the ability to effectively impede the infection caused by SARS-CoV-2. Nonetheless, the predictive capability of ADAM17 in predicting the severity of COVID-19 outcomes remains less certain within human populations.What this study addsUsing large genome wide association studies, Mendelian randomization study demonstrated that genetic susceptibility to the increased circulating levels of ADAM17 (extracellular domain) were associated with critical COVID-19 but not SARS-CoV-2 infection or hospitalized COVID-19.How this study might affect research, practice or policyThe study’s insights might pave the way for novel therapeutic strategies targeting ADAM17 activity. Patients with a genetic predisposition to higher ADAM17 activity might be identified and given tailored treatments.
Conserved and species-specific transcriptional responses to daily programmed resistance exercise in rat and mouse
Authors: Viggars Mark R , Sutherland Hazel , Cardozo Christopher P , Jarvis Jonathan C 
Published: August 2023

AbstractMice are often used in gain or loss of function studies to understand how genes regulate metabolism and adaptation to exercise in skeletal muscle. Once-daily resistance training with electrical nerve stimulation produces hypertrophy of the dorsiflexors in rat, but not in mouse. Using implantable pulse generators, we assessed the acute transcriptional response (1-hour post exercise) after 2, 10 and 20 days of training in free living mice and rats using identical nerve stimulation paradigms. RNA-sequencing revealed strong concordance in the timecourse of many transcriptional responses in the tibialis anterior muscles of both species including responses related to ‘stress responses/immediate-early genes’, and ‘collagen homeostasis’, ‘ribosomal subunits’, ‘autophagy’ and ‘focal adhesion’. However, pathways associated with energy metabolism including ‘carbon metabolism’, ‘oxidative phosphorylation’, ‘mitochondrial translation’, ‘propanoate metabolism’ and ‘valine, leucine and isoleucine degradation’ were oppositely regulated between species. These pathways were suppressed in the rat but upregulated in the mouse. Our transcriptional analysis suggests that although many pathways associated with growth show remarkable similarities between species, absence of an actual growth response in the mouse may be because the mouse prioritises energy metabolism, specifically replenishment of fuel stores and intermediate metabolites.
Neural specialization for ‘visual’ concepts emerges in the absence of vision
Authors: Hauptman Miriam , Elli Giulia , Pant Rashi , Bedny Marina 
Published: August 2023

AbstractVision provides a key source of information about many concepts, including ‘living things’ (e.g.,tiger) and visual events (e.g.,sparkle). According to a prominent theoretical framework, neural specialization for different conceptual categories is shaped by sensory features, e.g., living things are neurally dissociable from navigable places because living things concepts depend more on visual features. We tested this framework by comparing the neural basis of ‘visual’ concepts across sighted (n=22) and congenitally blind (n=21) adults. Participants judged the similarity of words varying in their reliance on vision while undergoing fMRI. We compared neural responses to living things nouns (birds, mammals) and place nouns (natural, manmade). In addition, we compared visual event verbs (e.g., ‘sparkle’) to non-visual events (sound emission, hand motion, mouth motion). People born blind exhibited distinctive univariate and multivariate responses to living things in a temporo-parietal semantic network activated by nouns, including the precuneus (PC). To our knowledge, this is the first demonstration that neural selectivity for living things does not require vision. We additionally observed preserved neural signatures of ‘visual’ light events in the left middle temporal gyrus (LMTG+). Across a wide range of semantic types, neural representations of sensory concepts develop independent of sensory experience.Significance StatementVision offers a key source of information about major conceptual categories, including animals and light emission events. Comparing neural signatures of concepts in congenitally blind and sighted people tests the contribution of visual experience to conceptual representation. Sighted and congenitally blind participants heard ‘visual’ nouns (e.g., ‘tiger’) and verbs (e.g., ‘sparkle’), as well as less visual nouns (e.g., ‘barn’) and verbs (e.g., ‘squeak’) while undergoing fMRI. Contrary to previous claims, both univariate and multivariate approaches reveal similar representations of animals and light emission verbs across groups. Across a broad range of semantic types, ‘visual’ concepts develop independent of visual experience. These results challenge theories that emphasize the role of sensory information in conceptual representation.
Distributed representations of behavior-derived object dimensions in the human visual system
Authors: Contier O. , Baker C.I. , Hebart M.N. 
Published: August 2023

AbstractObject vision is commonly thought to involve a hierarchy of brain regions processing increasingly complex image features, with high-level visual cortex supporting object recognition and categorization. However, object vision supports diverse behavioral goals, suggesting basic limitations of this category-centric framework. To address these limitations, we mapped a series of dimensions derived from a large-scale analysis of human similarity judgments directly onto the brain. Our results reveal broadly distributed representations of behaviorally-relevant information, demonstrating selectivity to a wide variety of novel dimensions while capturing known selectivities for visual features and categories. Behavior-derived dimensions were superior to categories at predicting brain responses, yielding mixed selectivity in much of visual cortex and sparse selectivity in category-selective clusters. This framework reconciles seemingly disparate findings regarding regional specialization, explaining category selectivity as a special case of sparse response profiles among representational dimensions, suggesting a more expansive view on visual processing in the human brain.
African bush pigs exhibit porous species boundaries and appeared in Madagascar concurrently with human arrival
Authors: Balboa Renzo F. , Bertola Laura D. , Brüniche-Olsen Anna , Rasmussen Malthe Sebro , Liu Xiaodong , Besnard Guillaume , Salmona Jordi , Santander Cindy G. , He Shixu , Zinner Dietmar , Pedrono Miguel , Muwanika Vincent , Masembe Charles , Schubert Mikkel , Kuja Josiah , Quinn Liam , Garcia-Erill Genís , Rakotoarivony Rianja , Henrique Margarida , Lin Long , Wang Xi , Heaton Michael P. , Smith Timothy P. L. , Hanghøj Kristian , Sinding Mikkel-Holger S. , Atickem Anagaw , Chikhi Lounès , Roos Christian , Gaubert Philippe , Siegismund Hans R. , Moltke Ida , Albrechtsen Anders , Heller Rasmus 
Published: August 2023

AbstractSeveral African mammals exhibit a phylogeographic pattern where closely related taxa are split between West/Central and East/Southern Africa, but their evolutionary relationships and histories remain controversial. Bushpigs (Potamochoerus larvatus) and red river hogs (P. porcus) are recognised as separate species due to morphological distinctions, a perceived lack of interbreeding at contact, and putatively old divergence times, but historically, they were considered conspecific. Moreover, the presence of Malagasy bushpigs as the sole large terrestrial mammal shared with the African mainland raises intriguing questions about its origin and arrival in Madagascar. Analyses of 67 whole genomes revealed a genetic continuum between the two species, with putative signatures of historical gene flow, variableFSTvalues, and a recent divergence time (<500,000 years). Thus, our study challenges key arguments for splittingPotamochoerusinto two species and suggests their speciation might be incomplete. Our findings also indicate that Malagasy bushpigs diverged from southern African populations and underwent a limited bottleneck 1,000-5,000 years ago, concurrent with human arrival in Madagascar. These results shed new light on the evolutionary history of an iconic and widespread African genus and provide insight into the longstanding biogeographic puzzle surrounding the bushpig’s presence in Madagascar.
Absolute Quantification of Microbiota in Shotgun Sequencing Using Host Cells or Spike-Ins
Authors: Wallace Andrew , Ling Hong , Gatenby Sean , Pruden Seren , Neeley Catherine , Harland Chad , Couldrey Christine 
Published: August 2023

ABSTRACTBackgroundAn ongoing challenge for DNA sequencing of samples containing microorganisms is the ability to meaningfully compare different samples and to connect the results back to clinically relevant disease states. The reads of DNA sequence from each sample do not, in and of themselves, give sufficient information to calculate the absolute abundances of each observed organism. Using relative abundances alone is insufficient to determine whether absolute abundances have increased or decreased in the organisms of interest from one sample to the next. This is a well-studied problem in 16S sequencing, but solutions in shotgun sequencing are lacking. Here we show how spike-ins can be used in shotgun sequencing to calculate absolute abundances of organisms present. We also propose the use of the host cells already in the sample as an alternative calculation method. Mammalian host cells are typically of sufficient size that they can be easily and cheaply counted prior to sequencing by a variety of methods and combining this with sequencing data provides sufficient information to calculate the absolute abundances of microbial organisms.ResultsMicrobial abundances in the samples calculated via this method were consistent with manufacturer-stated values of microbial communities, with qPCR, and with our method tested against itself with regard the spike-in and host-cell based options.R2values on the log10scale in these tests ranged from 0.85 to 0.98, and the log10-RMSE ranged from 0.1 to 0.7.ConclusionsThe proposed method can consistently calculate absolute microbial abundances to within an order of magnitude. Both versions of the method, where spike-ins are added to the samples, or where host cells in the sample are counted, are viable. Calculating absolute abundances allows for direct comparisons to be made between different samples. If disease-thresholds have been identified, absolute abundances can quantify disease states.