bluuebunny/crossref_metadata_2025_split huggingface dataset:
varVAMP: automated pan-specific primer design for tiled full genome sequencing and qPCR of highly diverse viral pathogens
Authors: Fuchs Jonas , Kleine Johanna , Schemmerer Mathias , Kreibich Julian , Maier Wolfgang , Battur Namuun , Krannich Thomas , Sedaghatjoo Somayyeh , Jaki Lena , Maks Anastasija , Boehm Christina , Wilhelm Carina , Schulze Jessica , Mache Christin , Berger Elischa , Panajotov Jessica , Eidenschink Lisa , Grüning Björn , Bauswein Markus , Böttcher Sindy , Johne Reimar , Wenzel Jürgen , Hölzer Martin , Panning Marcus 
Published: May 2024

ABSTRACTTime- and cost-saving surveillance of viral pathogens is achieved by tiled sequencing in which a viral genome is amplified in overlapping PCR amplicons and qPCR. However, designing pan-specific primers for viral pathogens that have high genomic variability represents a major challenge. Here, we present a bioinformatics command-line tool, called varVAMP (variablevirusamplicons). It relies on multiple sequence alignments of highly variable virus sequences and enables automatic pan-specific primer design for qPCR or tiled amplicon whole genome sequencing.The varVAMP software guarantees pan-specificity by two means: it designs primers in regions with minimal variability and introduces degenerate nucleotides into primer sequences to compensate for common sequence variations. We demonstrate varVAMP’s utility by designing and evaluating novel pan-specific primer schemes suitable for sequencing the genomes of SARS-CoV-2, Hepatitis E virus, rat Hepatitis E virus, Hepatitis A virus, Borna-disease-virus-1, and Poliovirus. Moreover, we established highly sensitive and specific Poliovirus qPCR assays that could potentially simplify current Poliovirus surveillance. Importantly, wet-lab and bioinformatic techniques established for SARS-CoV-2 tiled amplicon sequencing were readily transferable to these new primer schemes and will allow sequencing laboratories to extend their established methodology to other human pathogens.
Mismatch between pollen and pistil size causes asymmetric mechanical reproductive isolation acrossPhloxspecies
Authors: Feller Anna F. , Burgin Grace , Lewis Nia , Prabhu Rohan , Hopkins Robin 
Published: May 2024

AbstractIn flowering plants, pollen-pistil interactions can serve as an important barrier to reproduction between species. As the last barrier to reproduction before fertilization, interactions between these reproductive organs are both complex and important for determining a suitable mate. Here, we test whether differences in style length generate a post-mating prezygotic mechanical barrier between five species of perennialPhloxwildflowers with geographically overlapping distributions. We perform controlled pairwise reciprocal crosses between three species with long styles and two species with short styles to assess crossing success (seed set). We find that heterospecific seed set is broadly reduced compared to conspecific cross success and reveal a striking asymmetry in heterospecific crosses between species with different style lengths. To determine the mechanism underlying this asymmetric reproductive isolating barrier we assess pollen tube growthin vitroandin vivo. We demonstrate that pollen tubes of short-styled species do not grow long enough to reach the ovaries of long-styled species. We find that short-styled species also have smaller pollen and that both within and between species pollen diameter is highly correlated with pollen tube length. Our results support the hypothesis that the small pollen of short-styled species lacks resources to grow pollen tubes long enough to access the ovaries of the long-styled species, resulting in an asymmetrical, mechanical barrier to reproduction. Such mechanisms, combined with additional pollen-pistil incompatibilities, may be particularly important for closely related species in geographic proximity that share pollinators.
In vitroassays for clinical isolates of sequence type 131Escherichia colido not recapitulatein vivoinfectivity using a murine model of urinary tract infection
Authors: Rudick Courtney P. , Cox Rachel S. , Bourret Travis J. , Hanson Nancy D. 
Published: May 2024

AbstractSequence Type 131 isolates are a major cause of cystitis and pyelonephritis. Many studies rely solely onin vitroassays to screen for bacterial virulence factors associated with the pathogenicity of clinical isolates ofE. coli. Few studies have comparedin vitrofindings toin vivoinfectivity of clinical isolates. The purpose of this study was to evaluate the correlation betweenin vitroassays with the ability to cause cystitis and pyelonephritis in a murine model of urinary tract infection.In vitroassays were conducted according to published protocols and included: motility assays, biofilm formation, epithelial cell adhesion and invasion, and curli production. Twenty-one UPEC isolates ofE. coliST131 and non-ST131 were used for bothin vivoandin vitrostudies. Six mice per isolate were inoculated via urethral catheterization. CFUs were determined from bladder and kidneys.In vitroandin vivocorrelations were evaluated by multiple linear regression analysis. Pairwise linear regressions showed trendlines with weak positive correlations for motility, adhesion, and invasion and weak negative correlations for hemagglutination, biofilm and curli production. The ability ofE. coliST131 and non-ST131 clinical isolates to cause cystitis and pyelonephritis varies among strains. The R2Pearson Correlation value was less than ±0.5 for any pair, indicating little to no statistical association betweenin vitroandin vivofindings. These data showin vitrodata are not predictive of the ability of ST131E. colito infect and/or cause disease in a mouse model.Author summaryUrinary tract infections affect 150 million people annually andE. coliST131 have become the pandemic strain responsible for a majority of UTI, cystitis, and pyelonephritis cases. How ST131E. colihave become such prolific strain still remains to be elucidated. When evaluating bacterial pathogenicity, it is customary practice to usein vitroassays to predict isolate virulence and mechanisms of fitness, due to the lower cost, and relative ease of experimentation compared to more costly and complicatedin vivomodels. It is also common to use model organisms like pathogenicE. coliCFT073 or non-pathogenic lab strains such as BW25113 as representatives for the entire species. However, our research has shown that not only are model organisms substantially different from clinical isolates of ST131E. coli, butin vitroassays are poor predictors of clinical isolates’ ability to cause infection in a murine model of UTI. As such, research into the mechanisms of fitness for ST131 infectivity need to veer away from studying only model organisms and focus on utilizing pathogenic clinical isolates in conditions that more closely recapitulate urinary tract environmental niches.
Enhanced binding of guanylated poly(A) RNA by the LaM domain of LARP1
Authors: Kozlov Guennadi , Jiang Jianning , Rutherford Tyler , Noronha Anne M. , Wilds Christopher J. , Gehring Kalle 
Published: May 2024

ABSTRACTLa-related proteins (LARPs) are a family of RNA-binding proteins that share a conserved La motif (LaM) domain. LARP1 plays a role in regulating ribosomal protein synthesis and stabilizing mRNAs and has a unique structure without an RNA binding RRM domain adjoining the LaM domain. In this study, we investigated the physical basis for LARP1 specificity for poly(A) sequences and observed an unexpected bias for sequences with single guanines. Multiple guanine substitutions did not increase the affinity, demonstrating preferential recognition of singly guanylated sequences. We also observed that the cyclic di- nucleotides in the cCAS/STING pathway, cyclic-di-GMP and 3’,3’-cGAMP, bound with sub-micromolar affinity. Isothermal titration measurements were complemented by high-resolution crystal structures of the LARP1 LaM with six different RNA ligands, including two stereoisomers of a phosphorothioate linkage. The selectivity for singly substituted poly(A) sequences suggests LARP1 may play a role in the stabilizing effect of poly(A) tail guanylation.
Laser NIR irradiation enhances antimicrobial photodynamic inactivation of biofilms ofStaphylococcus aureus
Authors: Mamone Leandro , Tomás Roberto , Di Venosa Gabriela , Gándara Lautaro , Durantini Edgardo , Buzzola Fernanda , Casas Adriana 
Published: May 2024

ABSTRACTPhotodynamic inactivation (PDI) utilizes a photosensitizer (PS) activated by visible light to generate reactive oxygen species (ROS), to kill bacteria. PDI is effective against planktonic microorganisms, but biofilms are less sensitive due to limited PS and oxygen penetration. Near-infrared treatment (NIRT), involve the use of near-infrared light to kill bacteria either via thermal effects or ROS production.Our objective was to enhanceS. aureusbiofilm’s sensitivity to PDI by pre-treating with NIR irradiation before visible light exposure.In anin vitrobiofilm model, laser NIRT (980 nm) followed by exposure to PDI, showed a synergistic effect on bacterial viability loss (4-log CFU vs 1-log loss with individual treatments). Interestingly, pre-heating liquid medium had no significant impact on PDI efficacy, suggesting that both thermal and non-thermal effects of NIR may be involved.NIRT increased PS uptake, induced clefts in the biofilm matrix, and released bacterial cells from the biofilm. NIRT induced a transient increase in the temperature to 46°C ofin vitrocultures, however under the same conditions, when mice were irradiated, skin temperature rose to 37°.Our findings suggest that NIR irradiation serves as a complementary treatment to PDI, allowing reducing PS concentration, and highlighting its potential as an effective and resource-efficient antibacterial approach.
The roles of TGFβ and serotonin signaling in regulating proliferation of oocyte precursors and germline aging
Authors: Aprison Erin Z. , Dzitoyeva Svetlana , Ruvinsky Ilya 
Published: May 2024

AbstractThe decline of oocyte quality in aging but otherwise relatively healthy individuals compels a search for underlying mechanisms. Building upon a finding that exposure to male pheromone ascr#10 improves oocyte quality inC. elegans, we uncovered a regulatory cascade that promotes proliferation of oocyte precursors in adults and regulates oocyte quality. We found that the male pheromone promotes proliferation of oocyte precursors by upregulating LAG-2, a ligand of the Notch-like pathway in the germline stem cell niche. LAG-2 is upregulated by a TGFβ-like ligand DAF-7 revealing similarity of regulatory mechanisms that promote germline proliferation in adults and larvae. A serotonin circuit that also regulates food search and consumption upregulates DAF-7 specifically in adults. The serotonin/DAF-7 signaling promotes germline expansion to compensate for oocyte expenditure which is increased by the male pheromone. Finally, we show that the earliest events in reproductive aging may be due to declining expression of LAG-2 and DAF-7. Our findings highlight neuronal signals that promote germline proliferation in response to the environment and argue that deteriorating oocyte quality may be due to reduced neuronal expression of key germline regulators.
An unbiased method to partition diverse neuronal responses into functional ensembles reveals interpretable population dynamics during innate social behavior
Authors: Lin Alexander , Akafia Cyril , Dal Monte Olga , Fan Siqi , Fagan Nicholas , Putnam Philip , Tye Kay M. , Chang Steve , Ba Demba , Allsop AZA Stephen 
Published: May 2024

AbstractIn neuroscience, understanding how single-neuron firing contributes to distributed neural ensembles is crucial. Traditional methods of analysis have been limited to descriptions of whole population activity, or, when analyzing individual neurons, criteria for response categorization varied significantly across experiments. Current methods lack scalability for large datasets, fail to capture temporal changes and rely on parametric assumptions. There’s a need for a robust, scalable, and non-parametric functional clustering approach to capture interpretable dynamics. To address this challenge, we developed a model-based, statistical framework for unsupervised clustering of multiple time series datasets that exhibit nonlinear dynamics into ana-priori-unknown number of parameterized ensembles called Functional Encoding Units (FEUs). FEU outperforms existing techniques in accuracy and benchmark scores. Here, we apply this FEU formalism to single-unit recordings collected during social behaviors in rodents and primates and demonstrate its hypothesis-generating and testing capacities. This novel pipeline serves as an analytic bridge, translating neural ensemble codes across model systems.
Neural correlates of rapid familiarization to novel taste
Authors: Svedberg Daniel A. , Katz Donald B. 
Published: May 2024

AbstractThe gustatory cortex (GC) plays a pivotal role in taste perception, with neural ensemble responses reflecting taste quality and influencing behavior. Recent work, however, has shown that GC taste responses change across sessions of novel taste exposure in taste-naïve rats. Here, we use single-trial analyses to explore changes in the cortical taste-code on the scale of individual trials. Contrary to the traditional view of taste perception as innate, our findings suggest rapid, experience-dependent changes in GC responses during initial taste exposure trials. Specifically, we find that early responses to novel taste are less “stereotyped” and encode taste identity less reliably compared to later responses. These changes underscore the dynamic nature of sensory processing and provides novel insights into the real-time dynamics of sensory processing across novel-taste familiarization.
A novel, high throughput, and low-cost method for the detection of 40 amines relevant to inborn errors of metabolism, in under 60 minutes, using reverse phase high performance liquid chromatography
Authors: Wilson Kirkland A , Zhou Yun , Cunningham Gary , Chapman Kimberly , Summar Marshall , Regier Debra 
Published: May 2024

AbstractObjectivesAn assessment of amino acid and amine concentrations is important for the diagnosis and management of inborn errors of metabolism (IEMs). Methods exist that measure these biologically important metabolites but are cost-prohibitive and/or time consuming. We therefore sought to develop a novel methodology, applicable to IEMs, that is both high-throughput and low cost.MethodsPreviously, we developed a methodology for rapid, repeatable, and cost-efficient separation of approximately 20 amines as a proof of concept and now expand it to amines relevant to IEMs. We describe our separation methodology using reverse phase high performance liquid chromatography with ultraviolet-visible spectrum absorbance paired with precolumn derivatization witho-phthaladehyde.ResultsWe show reproducibility via concentration assessments, in triplicate, for each amine. We assess amines in prepared standard solutions and in biologic samples from patients with IEMs. We also detected and assessed the amino group containing compounds oxidized and reduced glutathione and ammonia. Validation was established using absolute area under the curve (AUC) and via comparison using a single internal standard.ConclusionsWe report good separation of 40 primary amino group containing metabolites, in a single, less than 60-minute run. This rapid, low cost, and accurate methodology only requires a small volume of sample and can greatly increase availability and access. Finally, the numerous disease associated amines (ie homocitrulline, trimethyllysine, alloisoleucine) and unique compounds detected in our single run has broad research and clinical utility and can increase efficiency, important as the need for analysis of amines grows globally.
Single unit-derived connectivity networks in tuberous sclerosis complex reveal propensity for network hypersynchrony driven by tuber-tuber interactions
Authors: Chari Aswin , Hernan Amanda E , Mahoney J Matthew , Thornton Rachel , Tahir M Zubair , Tisdall Martin M , Scott Rod C 
Published: May 2024

AbstractNetwork hypersynchrony is emerging as an important system-level mechanism underlying seizures, as well as cognitive and behavioural impairments, in children with structural brain abnormalities. We investigated patterns of single neuron action potential behaviour in 206 neurons recorded from tubers, transmantle tails of tubers and normal looking cortex in 3 children with tuberous sclerosis. The patterns of neuronal firing, on a neuron-by-neuron (autocorrelation) basis did not reveal any differences as a function of anatomy. However, at the level of functional networks (cross-correlation), there is a much larger propensity towards hypersynchrony of tuber-tuber neurons that in neurons from any other anatomical site. This suggests that tubers are the primary drivers of adverse outcomes in children with tuberous sclerosis.
Housing instability among young men who have sex with men in a US national sample
Authors: Sisselman-Borgia Amanda , Patel Viraj V , Grov Christian 
Published: May 2024

AbstractBackgroundYouth, including those experiencing housing instability, are among the fastest growing groups of individuals with new STI diagnoses, including HIV. The unpredictable nature of the lives of youth experiencing housing instability often leads to inconsistent or non-existent health care and preventive follow up, leaving gaps in our knowledge about the most prominent needs for intervention.MethodsUsing data from theTogether 5000(T5K) study, we examined factors associated with housing instability in a sample of 2,228 youth between the ages of 16-24 who identified as sexual and gender minority (SGM) men having sex with men. Logistic regression was used to assess the most prominent factors associated with housing instability. The model included seven significant factors - former peer victimization, gender, age, sex work, IPV, social support, and health insurance status.FindingsParticipants who reported more behavioral risk factors for STI and those who reported sex work in the last three months were more likely to experience housing instability (OR = 2.5 and 2.76 respectively). Youth with higher levels of reported social support, health insurance, and older age were more likely to report stable housing (OR = .98, 1.61, and 1.13 respectively). Surprisingly, youth with stable housing were more likely to report intimate partner violence than those experiencing housing instability (OR = .89).DiscussionImplications for addressing STIs among adolescent SGM men having sex with men are discussed including bolstering support systems and addressing basic needs deficits and trauma associated with sex work and behavioral risk factors for STI.Implications and contributions statementThe study examines correlates of housing instability among a sample of young sexual and gender minority men who have sex with other men. Correlates of housing instability included behavioral risk factors for sexually transmitted infection and reporting sex work in the last three months. Health insurance, older age, and higher levels of social support were correlated with more stable housing.
One way or another, you’re not going to fit: Trans and gender diverse people’s perspectives on sexual health services in the United Kingdom
Authors: Witney Tom , Rait Greta , Saunders John , Hobbes Lorna , Mitchell Laura , Stewart Jay , McDonagh Lorraine 
Published: May 2024

AbstractObjectivesTrans and/or gender diverse (T/GD) people in the UK are less likely to access sexual health services (SHS) than cisgender people but are more likely to report negative experiences. The British Association for Sexual Health and HIV (BASHH) developed expert recommendations for T/GD-inclusive SHS, but these lack service user perspectives. This study addressed this gap by asking T/GD people how SHS could be T/GD-inclusive.MethodsSemi-structured interviews (n=31) and focus groups (n=21) were conducted with T/GD people aged 17-71 years old recruited through community organisations and social media, exploring experiences of SHS and inclusivity. Study design, materials, and analysis were informed by T/GD people and an advisory committee of charities and sexual health clinicians. Data were analysed using thematic analysis, managed using NVivo.ResultsParticipants often expected that SHS were not set up for T/GD people. This was reinforced by poor experiences in other healthcare settings and the lack of information on NHS websites. Some participants had been denied care because they were ‘too complex.’ Participants wanted to know that SHS had engaged with the needs of T/GD people and looked for hallmarks of inclusivity, such as Trans Pride flags in reception areas. Some participants wanted specialist T/GD services, but others preferred to access general SHS. Staff attitudes were a key factor underpinning inclusivity. Anticipating having their identity questioned or needs dismissed, participants sought kindness and openness. Although the needs of T/GD people are diverse and different from cisgender service users, participants stressed that SHS staff already had the skills to deliver sensitive person-centred care and emphasised the value of inclusive SHS.ConclusionThese findings provide insight into what a sample of T/GD people in the UK consider important for T/GD-inclusive SHS. Participants’ suggestions aligned with and reinforce BASHH expert recommendations. Importantly, they highlight the need for ongoing engagement to deliver T/GD-inclusive SHS.Key messagesWhat is already known on this topicTrans and/or gender diverse people are less likely to engage with sexual health services than cis-gender peopleThe British Association for Sexual Health and HIV (BASHH) Gender and Sexual Minority Special Interest Group (GSM SIG) has developed expert recommendations for trans-inclusive sexual health services, but user perspectives are missingWhat this study addsParticipant suggestions and preferences for inclusive services support BASHH GSM recommendationsParticipants looked for inclusive SHS thatrecognise, understand and affirmtheir needsHow this study might affect research, practice or policyEnhancing T/GD inclusivity involvesactive engagementwithclinical spaces, processes and delivery