bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual cases of Parkinson’s disease can be robustly classified by cortical oscillatory activity from magnetoencephalography
Authors: Roberts Gillian , Hardy Samuel , Chen Robert , Dunkley Benjamin T ,   PREVENT-AD Research Group & Quebec Parkinson Network
Published: August 2024

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder which causes debilitating symptoms in both the motor and cognitive domains. The neurophysiological markers of PD include ‘oscillopathies’ such as diffuse neural oscillatory slowing, dysregulated beta band activity, and changes in interhemispheric functional connectivity; however, the relative importance of these markers as determinants of disease status is not clear. In this study, we used resting state magnetoencephalography data (n = 199 participants, 78 PD, 121 controls) from the open OMEGA repository to investigate changes in spectral power and functional networks in PD. Using a Contrast of Parameter Estimates (COPE) approach, we modelled the effects of PD while controlling for population-level confounds (age, sex, brain volume). Permutation testing revealed highly significant increases in theta (p=0.0001) and decreases in gamma band spectral power (p=0.0001). Building on the group contrast results, we investigated the ability of source-resolved MEG data to distinguish PD from healthy controls. Our approach uses a Partial Least Squares (PLS)-based classifier to find linear combinations of MEG features which independently predict PD. We found MEG-based predictions to be highly sensitive and specific, reaching an optimal AUC-ROC of 0.87 ± 0.04 using a model including spectral power features with 4 independent PLS components, compared to 0.68 ± 0.04 when using functional connectivity. Interpretation of the model weights suggests that oscillatory slowing can be separated into independent posterior theta and global diffuse delta components that can robustly identify individual cases of PD with a high degree of accuracy. This suggests MEG can reveal dissociable, complementary neural processes which contribute to PD.
Stigma among people living with HIV in Northern Egypt
Authors: Magdy Mona , Zaki Adel , Osman Sherif Omar , Abd El-Wahab Ekram W. , Abd Elhameed Asmaa 
Published: August 2024

AbstractStigma involves labeling individuals, and associating them with negative behavior, leading to social isolation, stereotypes, loss of status, and discrimination. HIV stigma is considered a major barrier to effective responses to the HIV/AIDS epidemic. We aimed in this study to assess the stigma among people living with HIV (PLWH) in Alexandria, Egypt. We conducted a cross-section study on 785 PLWH attending the HIV unit in Alexandria Fever Hospital. Data collection was done through an interviewing questionnaire and an Arabic-translated version of the standardized, 12-item short version of the HIV Stigma Scale. The stigma scale was highly reliable (alpha coefficient = 0.743). About 72.4% of participants had high stigma with a total stigma score of more than 30. Men showed a higher median stigma score than women (60.8% vs 23.0% respectively recorded a median score of 33 or more). The total stigma score was significantly associated with the male sex and residing in Alexandria city (p= <0.1).In conclusion, PLWH in Egypt experience a significant degree of stigma. These data can guide future health interventions to provide psychological and social support for PLWH.
HIF-α signaling regulates the macrophage inflammatory response duringLeishmania majorinfection
Authors: Fry Lucy G. , Washam Charity L. , Roys Hayden , Bowlin Anne K. , Venugopal Gopinath , Bird Jordan T. , Byrum Stephanie D. , Weinkopff Tiffany 
Published: August 2024

AbstractCutaneous leishmaniasis (CL) contributes significantly to the global burden of neglected tropical diseases, with 12 million people currently infected withLeishmaniaparasites. CL encompasses a range of disease manifestations, from self-healing skin lesions to permanent disfigurations. Currently there is no vaccine available, and many patients are refractory to treatment, emphasizing the need for new therapeutic targets. Previous work demonstrated macrophage HIF-α-mediated lymphangiogenesis is necessary to achieve efficient wound resolution during murineL. majorinfection. Here, we investigate the role of macrophage HIF-α signaling independent of lymphangiogenesis. We sought to determine the relative contributions of the parasite and the host-mediated inflammation in the lesional microenvironment to myeloid HIF-α signaling. Because HIF-α activation can be detected in infected and bystander macrophages in leishmanial lesions, we hypothesize it is the host’s inflammatory response and microenvironment, rather than the parasite, that triggers HIF-α activation. To address this, macrophages from mice with intact HIF-α signaling (LysMCreARNTf/+) or mice with deleted HIF-α signaling (LysMCreARNTf/f) were subjected to RNASequencing afterL. majorinfection and under pro-inflammatory stimulus. We report thatL. majorinfection alone is enough to induce some minor HIF-α-dependent transcriptomic changes, while infection withL. majorin combincation with pro-inflammatory stimuli induces numerous transcriptomic changes that are both dependent and independent of HIF-α signaling. Additionally, by coupling transcriptomic analysis with several pathway analyses, we found HIF-α suppresses pathways involved in protein translation duringL. majorinfection in a pro-inflammatory environment. Together these findings showL. majorinduces a HIF-α-dependent transcriptomic program, but HIF-α only suppresses protein translation in a pro-inflammatory environment. Thus, this work indicates the host inflammatory response, rather than the parasite, largely contributes to myeloid HIF-α signaling duringLeishmaniainfection.
Rate of force development is correlated with corticospinal excitability during explosive voluntary contractions
Authors: Castelli Federico , Mian Omar S. , Bruton Adam , Chembila Valappil Ashika C. , Hannah Ricci , Tillin Neale A. 
Published: August 2024

AbstractObjectiveTo investigate the relationship between rate of torque development (RTD) and corticospinal excitability (denoted by motor-evoked potential; MEP) during explosive voluntary contractions. Also, to assess differences in MEP and silent period duration between different phases of explosive contraction and at maximum voluntary contraction (MVC) plateau.MethodsIn 14 adults, quadriceps muscle MEP and silent period duration were measured at ∼45 (early), ∼115 (middle), and ∼190 ms (late) from EMG onset during knee-extensor isometric explosive contractions, and at MVC plateau with superimposed transcranial magnetic stimulation (TMS). RTD was measured immediately prior to early-phase MEP during the same contractions, and these two variables were correlated across separate contractions, within participants, via repeated measures correlation (RmCorr). RTD was also measured in explosive contractions without TMS over early-, middle-, and late-phases and correlated to MEP averaged across the corresponding and preceding phases, via Pearson’s r correlations, assessing relationships across participants. MEP and silent period duration were compared (ANOVA) between the different phases and at MVC plateau.ResultsMEP and RTD were correlated across separate contractions within participants (RmCorr r=0.43), and in the middle phase across participants (Pearson’s r=0.56). MEP and RTD were not correlated in other phases (r≥0.09). Silent period duration increased throughout the different phases of contraction and up to MVC plateau (ANOVA, p=0.001) but MEP remained constant (ANOVA, p=0.42).ConclusionThe correlations between MEP and RTD suggests corticospinal excitability is an important determinant of RTD. During rapid torque development and up to MVC plateau, corticospinal inhibition increases but excitability remains constant.
Genome-wide Search for Gene Mutations likely Conferring Insecticide Resistance in the Common Bed Bug,Cimex lectularius
Authors: Toga Kouhei , Kimoto Fumiko , Fujii Hiroki , Bono Hidemasa 
Published: August 2024

AbstractInsecticide resistance in the bedbugCimex lectulariusis poorly understood due to the lack of genome sequences for resistant strains. In Japan, we identified a resistant strain ofC. lectulariusthat exhibits a higher pyrethroid resistance ratio compared to many previously discovered strains. We sequenced genomes of the pyrethroid resistant and susceptible strains using long-read sequencing, resulting in the construction of highly contiguous genomes (N50 of resistant strain: 2.1Mb and N50 of susceptible strain: 1.5 Mb). Gene prediction was performed by BRAKER3 and Functional annotation was performed by Fanflow4insects workflow. Next, we compared their amino acid sequences to identify gene mutations, identifying 729 mutated transcripts that were specific to the resistant strain. Among them, those defined previously as resistance genes were included. Additionally, enrichment analysis implicated DNA damage response, cell cycle regulation, insulin metabolism, and lysosomes in the development of pyrethroid resistance. Genome editing of these genes can provide insights into the evolution and mechanisms of insecticide resistance. This study expanded the target genes to monitor allele distribution and frequency changes, which will likely contribute to the assessment of resistance levels. These findings highlight the potential of genome-wide approaches to understand insecticide resistance in bed bugs.Simple SummaryBedbugs have expanded globally over the past two decades, causing several health risks. Mutations in their genes allow bed bugs to develop insecticide resistance. However, the extent to which gene mutations exist in the bug genome remains largely unknown because the genomes of resistant strains have not been determined. We accurately sequenced the genomes of both susceptible and resistant strains and compared the gene sequences between the two strains. Several genes with resistance-specific mutations have been identified. These mutations can alter gene function and lead to insecticide resistance.
Early steps of the biosynthesis of the anticancer antibiotic pleurotin
Authors: Weaver Jack A. , Alkhder Duha , Prasongpholchai Panward , Tadesse Michaël D. , de los Santos Emmanuel L. , Song Lijiang , Corre Christophe , Alberti Fabrizio 
Published: August 2024

AbstractPleurotin is a meroterpenoid specialised metabolite made by the fungusHohenbuehelia grisea, and it is a lead anticancer molecule due to its irreversible inhibition of the thioredoxin-thioredoxin reductase system. Total synthesis of pleurotin has previously been achieved, including through a stereoselective route, however its biosynthesis has not been characterised. In this study, we used isotope-labelled precursor feeding to show that the non-terpenoid quinone ring of pleurotin and its congeners is derived from phenylalanine. We sequenced the genome of the pleurotin-producing fungus and used comparative transcriptomics to identify putative genes involved in pleurotin biosynthesis. Additionally, the heterologous expression of a UbiA-like prenyltransferase fromH. grisearesulted in the isolation and characterisation of the first predicted pleurotin biosynthetic intermediate, 3-farnesyl-4-hydroxybenzoic acid. This work sets the foundation to fully elucidate the biosynthesis of pleurotin and its congeners, with long-term potential to optimise their production for therapeutic use and engineer the pathway towards the biosynthesis of valuable analogues.
Artificial selection for adult predation survival impacts life history and morphology in guppies (Poecilia reticulata)
Authors: De Waele Hannah , Vega-Trejo Regina , Vila-Pouca Catarina , Noordenbos Jori , Phillips Elizabeth , Pollux Bart J.A. , Kotrschal Alexander 
Published: August 2024

AbstractPredation is accepted as a major evolutionary driver of life history and morphology. However, whether these traits evolve directly via predation or via indirect effects is largely unresolved. We used artificial selection over three generations to experimentally test the impact of adult predation on the evolution of life history and morphology in guppies (Poecilia reticulata). We found that, compared to control fish, predation-selected fish produced larger offspring and larger broods early in life. However, other life history parameters, such as interbrood interval and total number of offspring, showed no response. We also found that predation-selected for smaller and lighter females and for shorter tails and gonopodia in males, with no effect on body colouration. Our results show that while several traits evolve fast under selection on adult predation, several ‘classic’ predation-dependent traits seem unaffected by predation selection. By comparing our experimental results to those from natural populations we can disentangle the contribution of direct and indirect effects on trait evolution under predation pressure.
Development of a highly-sensitive method to detect the carriage of carbapenem-resistantPseudomonas aeruginosain humans
Authors: Shahab Selvi N. , van Veen Anneloes , Kempenaars Nikita , Rijfkogel Amber , Schmitt Heike , Saharman Yulia R. , Vos Margreet C. , Karuniawati Anis , Severin Juliëtte A. 
Published: August 2024

ABSTRACTCarbapenem-resistantPseudomonas aeruginosa(CRPA) causes severe and potentially life-threatening infections in hospitalized patients with mortality rates of more than 40%. To detect CRPA carriage in humans for surveillance purposes or to prevent spread and outbreaks in hospitals, a highly-sensitive culture method for CRPA carriage in humans is needed. We aimed to develop such a highly-sensitive method, that would be feasible in laboratories with limited resources. In this study, seven well-defined CRPA strains belonging to high-risk clones were used, including one CRPA without a carbapenemase gene and six carbapenem-resistant isolates with carbapenemase genes. We applied a stepwise approach wherein we included four enrichment broths and eightPseudomonas aeruginosa-selective culture media. Spiking experiments were performed to further evaluate the combination of the most sensitive enrichment broths and selective agar plates in human samples. The two most sensitive enrichments broths were TSB-vancomycin and TSB-vancomycin with 2 mg/L imipenem and the most sensitive selective agar plates werePseudomonasisolation agar Becton Dickinson,Pseudomonasisolation agar Sigma-Aldrich, and M-PA-C (Becton Dickinson). After the spiking experiment, the best method for detecting CRPA based on the sensitivity and the selectivity was the combination of TSB-vancomycin with 2 mg/L imipenem as an enrichment broth for overnight incubation, followed by subculturing the broth on M-PA-C agar plate. We have thus developed a highly-sensitive selective method to detect CRPA carriage in humans, which can also be applied in limited-resource laboratories. This may contribute to an overall effort to control CRPA.
The city and forest bird flock together in a common garden: genetic and environmental effects drive urban phenotypic divergence
Authors: Thompson M.J. , Réale D. , Chenet B. , Delaitre S. , Fargevieille A. , Romans M. , Caro S.P. , Charmantier A. 
Published: August 2024

AbstractUrban phenotypic divergences are documented across diverse taxa, but the underlying genetic and environmental drivers behind these phenotypic changes are unknown in most wild urban systems. We conduct a common garden experiment using great tit (Parus major) eggs collected along an urbanization gradient to: 1) determine whether documented morphological, physiological, and behavioural shifts in wild urban great tits are maintained in birds from urban and forest origins reared in a common garden (N = 73) and 2) evaluate how different sources of genetic, early maternal investment, and later environmental variation contributed to trait variation in the experiment. In line with the phenotypic divergence in the wild, common garden birds from urban origins had faster breath rates (i.e., higher stress response) and were smaller than birds from forest origins, while wild differences in aggression and exploration were not maintained in the experiment. Differences between individuals (genetic and environmentally induced) explained the most trait variation, while variation among foster nests and captive social groups was limited. Our results provide trait-specific evidence of evolution in an urban species where genetic change likely underlies urban differences in morphology and stress physiology, but that urban behavioural divergences are more strongly driven by plasticity.
Inpp5e Is Critical for Photoreceptor Outer Segment Maintenance
Authors: Gupta Mohona , Lewis Tylor R. , Stuck Michael W. , Spencer William J. , Klementieva Natalia V. , Arshavsky Vadim Y. , Pazour Gregory J. 
Published: August 2024

AbstractIn humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouseInpp5ewhere the gene was deleted either during outer segment formation or after outer segments were fully formed. In both cases, the loss of Inpp5e led to severe defects in photoreceptor outer segment morphology and ultimately photoreceptor cell loss. The primary morphological defect consisted of outer segment shortening and reduction in the number of newly forming discs at the outer segment base. This was accompanied by structural abnormalities of the Golgi apparatus, mislocalized rhodopsin, and an accumulation of extracellular vesicles. In addition, knockout cells showed a reduction in the size and prevalence of the actin network at the site of new disc morphogenesis and the occasional formation of membrane whorls instead of discs in a subset of cells. Together, these data demonstrate that Inpp5e plays a critical role in maintaining the outer segment and the normal process of outer segment renewal depends on the activity of this enzyme.
Microbiome diversity, intra-mucosal bacteria and immune integration within normal and asthmatic airway mucosa
Authors: Moffatt Miriam F. , Nishimura Tamiko , Cox Michael J. , McBrien Claire , Burke Conor , Cuthbertson Leah , Lewis Keir , Attanoos Richard , Davies Gwyneth , Chung Kian Fan , Robertus Jan Lukas , Ish-Horowicz Jonathan , O’Carroll Orla , Bozeman John M. , McGowan Aisling , Hopkin Julian M. , Lathrop G. Mark , Riazalhosseini Yasser , Cookson William O.C. 
Published: August 2024

AbstractAsthma is characterized by reduced bronchial bacterial diversity and airway mucosal disruption. We examined spatial distributions of microbial sequences and host mucosal transcripts in bronchial biopsies from healthy controls and adult asthmatics. Bacteria were discovered by 16S ribosomal RNA staining in the lamina propria of all biopsies, with counts positively associated to lumenal bacterial diversity. Weighted correlation network analysis identified fifteen co-expression networks, including distinct programs of adaptive and innate immunity in differing spatial distributions. Stromal bacterial counts correlated significantly with eight of the network eigenvectors in directions compatible with beneficial relationships. The results suggest that dysbiosis may affect mucosal immunity through impaired interactions beneath the epithelial border. Intra-mucosal companion bacteria may be a potential substrate for selective management of immunity in a wide range of diseases.One-Sentence SummaryThe lung microbiome extends within the airway mucosa and associates spatially and functionally with immune networks.
Tracing active members in microbial communities by BONCAT and click chemistry-based enrichment of newly synthesised proteins
Authors: Hellwig Patrick , Kautzner Daniel , Heyer Robert , Dittrich Anna , Wibberg Daniel , Busche Tobias , Winkler Anika , Reichl Udo , Benndorf Dirk 
Published: August 2024

AbstractA comprehensive understanding of microbial community dynamics is fundamental to the advancement of environmental microbiology, human health, and biotechnology. Metaproteomics, i.e. the analysis of all proteins in a microbial community, provides insights into these complex systems. Microbial adaptation and activity depend to an important extent on newly synthesized proteins (nP), however, the distinction between nP and bulk proteins is challenging. The application of bioorthogonal non-canonical amino acid tagging (BONCAT) with click chemistry has demonstrated efficacy in the enrichment of nP in pure cultures. However, the transfer of this technique to microbial communities has proven challenging and has therefore not been used on microbial communities before. To address this, a new workflow with efficient and specific nP enrichment was developed using a laboratory-scale mixture of labelledE. coliand unlabelled yeast. This workflow was successfully applied to an anaerobic microbial community with initially low BONCAT efficiency. A substrate shift from glucose to ethanol selectively enriched nP with minimal background. The identification of bifunctional alcohol dehydrogenase and a syntrophic interaction between an ethanol-utilizing bacterium and two methanogens (hydrogenotrophic and acetoclastic) demonstrates the potential of metaproteomics targeting nP to trace microbial activity in complex microbial communities.
Fibrilpaint targets amyloid fibrils for ubiquitination
Authors: Dekker Françoise A. , Pedrola Júlia Aragonès , Poza-Rodriguez Adriana , Mayer Guy , Singh Shalini , Heesink Gobert , Claessens Mireille M. A. E. , Friedler Assaf , Rüdiger Stefan G. D. 
Published: August 2024

AbstractNeurodegenerative diseases are characterised by the progressive loss of neuronal tissue, and the accumulation of amyloid fibrils. Currently, there are no therapeutics that remove these amyloids. Targeted protein degradation could be a promising strategy to remove fibrils or oligomeric precursors. This approach requires degraders that specifically recognise amyloid fibrils, preferentially in early stages. Here, we introduce FibrilPaint20 (FP20), a peptide that specifically mediates the ubiquitination of amyloid fibrils. It acts as a PROTAC, containing both of a fibril recognition module and a recruitment motif for the E3 ubiquitin ligase CHIP. Importantly, FP20 does not bind to the functional monomer but exclusively to fibrils. Remarkably, FP20 ubiquitinates a set chemically diverse fibrils, unrelated in sequence and morphology. This includes fibrils of the disease-related proteins of α-synuclein, Aβ, Huntingtin and various Tau species, such as patient-derived fibrils from Alzheimer, Frontotemporal Dementia and Corticobasal Degeneration. This makes FP20 interesting for targeting mixed pathologies. Together, FP20 is an attractive lead compound for targeted protein degradation of amyloid fibrils.
Bioorthogonal labeling of chitin in pathogenic Candida species reveals biochemical mechanisms of hyphal growth and homeostasis
Authors: Williams Caroline , Carnahan Bella R. , Hyland Stephen N. , Grimes Catherine L. 
Published: August 2024

AbstractPathogenic fungi rely on the cell wall component, chitin, for critical structural and immunological functions. Here a chitin labeling method to visualize the hyphal pathogenic response was developed. The data show that filamentous fungi,Candida albicans, transportN-acetylglucosamine (NAG) bio-orthogonal probes and incorporate them into the cell wall, indicating the probes utility forin vivostudy of the morphological, pathogenic switch. As yeast reside in complex microenvironments, The data show that the opportunistic microbeC. albicans, has developed processes to utilize surrounding bacterial cell wall fragments to initiate the morphogenic switch. The probes are utilized for visualization of growth patterns of pathogenic fungi, providing insights into novel mechanisms for the development of antifungals. Remodeling chitin in fungi using NAG derivatives will advance yeast pathogenic studies.