bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding the Microbiome-Metabolome Nexus: A Systematic Benchmark of Integrative Strategies
Authors: Mangnier Loïc , Bodein Antoine , Mariaz Margaux , Scott-Boyer Marie-Pier , Mathieu Alban , Vashist Neerja , Bramble Matthew S. , Droit Arnaud
Published: January 2024

Background

The exponential growth of high-throughput sequencing technologies was an incredible opportunity for researchers to combine various -omics within computational frameworks. Among these, metagenomics and metabolomics data have gained an increasing interest due to their involvement in many complex diseases. However, currently, no standard seems to emerge for jointly integrating both microbiome and metabolome datasets within statistical models.

Results

Thus, in this paper we comprehensively benchmarked nineteen different integrative methods to untangle the complex relationships between microorganisms and metabolites. Methods evaluated in this paper cover most of the researcher’s goals such as global associations, data summarization, individual associations, and feature selection. Through an extensive and realistic simulation we identified best methods across questions commonly encountered by researchers. We applied the most promising methods in an application to real gut microbial datasets, unraveling complementary biological processes involved between the two omics. We also provided practical guidelines for practitioners tailored to specific scientific questions and data types.

Conclusion

In summary, our work paves the way toward establishing research standards when mutually analyzing metagenomics and metabolomics data, building foundations for future methodological developments.
Macrophage Polarizations in the Placenta and Lung are Associated with Bronchopulmonary Dysplasia
Authors: Mestan Karen K. , Sharma Abhineet , Lazar Sarah , Pandey Sonalisa , Parast Mana M. , Laurent Louise C. , Prince Lawrence S. , Sahoo Debashis
Published: January 2024

The intricate interplay between macrophage polarization and placenta vascular dysfunction has garnered increasing attention in the context of placental inflammatory diseases. This study delves into the complex relationship between macrophage polarization within the placenta and its potential impact on the development of vascular dysfunction and inflammatory conditions. The placenta, a crucial organ in fetal development, relies on a finely tuned balance of immune responses for proper functioning. Disruptions in this delicate equilibrium can lead to pathological conditions, including inflammatory diseases affecting the fetus and newborn infant.

We explored the interconnectedness between placental macrophage polarization and its relevance to lung macrophages, particularly in the context of early life lung development. Bronchopulmonary dysplasia (BPD), the most common chronic lung disease of prematurity, has been associated with abnormal immune responses, and understanding the role of macrophages in this context is pivotal. The investigation aims to shed light on how alterations in placental macrophage polarization may contribute to lung macrophage behavior and, consequently, influence the development of BPD. By unraveling the intricate mechanisms linking macrophage polarization, placental dysfunction and BPD, this research seeks to provide insights that could pave the way for targeted therapeutic interventions. The findings may offer novel perspectives on preventing and managing placental and lung-related pathologies, ultimately contributing to improved maternal and neonatal health outcomes.
TTSBBC: Triplex Target Site Biomarkers and Barcodes in Cancer
Authors: Ylagan Maya , Xu Qi , Kowalski Jeanne
Published: January 2024

The technology of Triplex-forming oligonucleotides (TFOs) provides an approach to manipulate genes at the DNA level. TFOs bind to specific sites on genomic DNA, creating a unique intermolecular triple-helix DNA structure through Hoogsteen hydrogen bonding. This targeting by TFOs is site-specific and the locations TFOs bind are referred to as TFO target sites (TTS). Triplexes have been observed to selectively influence gene expression, homologous recombination, mutations, protein binding, and DNA damage. These sites typically feature a poly-purine sequence in duplex DNA, and the characteristics of these TTS sequences greatly influence the formation of the triplex. We introduce TTSBBC, a novel analysis and visualization platform designed to explore features of TTS sequences to enable users to design and validate TTSs. The web server can be freely accessed athttps://kowalski-labapps.dellmed.utexas.edu/TTSBC/.
Initial pig developmental stage influences intestinal organoid growth but not phenotype
Authors: Duchesne Camille , Randuineau Gwénaëlle , Normand Laurence Le , Romé Véronique , Laraqui Samia , Arnaud Alexis Pierre , Boudry Gaëlle
Published: January 2024

Intestinal organoids are promising tools in the context of animal experiment reduction. Yet, a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig, a valuable model of Humans. Organoids were derived from jejunal and colonic ISC obtained from 1, 7, 28, 36 and 180-day old pigs and passaged three times. We first confirmed by qPCR that the expression of 18% of the >80 studied genes related to various intestinal functions differed between jejunal and colonic organoids after two passages (P<0.05). Growth and morphology of organoids depended on intestinal location (greater number and larger organoids derived from colonic than jejunal ISC, P<0.05) but also pig age. Indeed, when ISC were derived from young piglets, the ratio of organoids to spheroids was greater (P<0.05), spheroids were larger during the primary culture but smaller after two passages (P<0.05) and organoids smaller after one passage (P>0.05) compared to ISC from older pigs. Finally, no difference in cellular composition, evaluated by immunostaining of markers of the major intestinal cell types (absorptive, enteroendocrine and goblet cells) were observed between organoids originating from 7 or 180-day old pigs, while difference between intestinal site origin were noticed. In conclusion, while the age of the tissue donor affected organoid growth and morphology, it did not influence their phenotype.
Silver nanoparticles can be sampled by ultrafiltration probe but elution into & recovery from plasma and DPBS differsin vitro
Authors: Risselada Marije , McCain Robyn R , Bates Miriam G , Anderson Makensie L
Published: January 2024

We compared 1) the influence of elution fluid on rate, pattern, and completeness of silver nanoparticle (AgNP) elution, and 2) ultrafiltration (UF) probe and direct samplingin vitro. Six specimens (2.5ml of 0.02mg/ml 10nm AgNP and 5.0ml of 30% poloxamer 407) contained in a dialysis tube (12-14kDa pores) were placed in 100ml Dulbecco’s Phosphate Buffered Saline (DPBS) (n=3) or canine plasma (n=3) for 96h on a stirred hot plate (37°C and 600rpm) and sampled 20 times. Six pipette and UF probe samples were taken of a 0.001mg AgNP/ml DPBS or plasma solution. Inductively coupled plasma mass spectrometry was used to analyze Ag. Stock plasma contained Ag. At 96h, 5/6 dialysis tubes had not fully released AgNP. One peak in hourly Ag increase was present in DPBS (10-13h), and two peaks in plasma (6-8h and 10-13h). The hourly Ag increase in plasma decreased earlier than in DPBS. UF probe sampling was possible in both DPBS and plasma and resulted in higher Ag concentrations but with more variation than pipette samples. Whilein vitrouse of DPBS might be more cost effective, plasma should be considered due to difference in elution and recovery.
Single-cell transcriptomics reveals colonic immune perturbations during amyloid-β driven Alzheimer’s disease in mice
Authors: Makhijani Priya , Emani Rohini , Aguirre Carlos Galicia , Mu Wei-Chieh , Rane Anand , Ng Jenny Hong Yu , Valentino Taylor R. , Manwaring-Mueller Max , Tan Christopher Ryan , Du Huixun , Wu Fei , Khan Saad , Wilson Kenneth A. , Winer Shawn , Wang Chao , Mortha Arthur , Furman David , Ellerby Lisa M. , Rojas Olga L. , Andersen Julie K. , Winer Daniel A.
Published: January 2024

The “gut-brain axis” is emerging as an important target in Alzheimer’s disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-β (Aβ) mouse model, we uncovered AD-associated changes in ribosomal activity, oxidative stress, and BCR/plasma cell activity. Strikingly, levels of colon CXCR4+antibody secreting cells (ASCs) were significantly reduced. This corresponded with accumulating CXCR4+B cells and gut-specific IgA+cells in the brain and dura mater, respectively. Consistently, a chemokine ligand for CXCR4, CXCL12, was expressed at higher levels in 5XFAD glial cells and in in silico analyzed human brain studies, supporting altered neuroimmune trafficking. An inulin prebiotic fiber diet attenuated AD markers including Aβ plaques and overall frailty. These changes corresponded to an expansion of gut IgA+cells and rescued peripheral Tregslevels. Our study points to a key glia-gut axis and potential targets against AD.

Study Highlights

AD is associated with altered immune parameters in the gut of5XFADmice.

5XFADcolon has reduced ASCs, including CXCR4+cells with a migratory gene signature.

5XFADbrain gliosis includes increased CXCL12 expression.

CXCR4+B cells and gut-specific IgA+ASCs accumulate in the5XFADbrain and/or dura mater.

Inulin diet attenuates AD disease parameters while boosting IgA+cell and Treglevels.
Spaceflight increases sarcoplasmic reticulum Ca2+leak and this cannot be counteracted with BuOE treatment
Authors: Braun Jessica L. , Fajardo Val A.
Published: January 2024

Spending time in a microgravity environment is known to cause significant skeletal muscle atrophy and weakness via muscle unloading, which can be partly attributed to Ca2+dysregulation. The sarco(endo)plasmic reticulum Ca2+ATPase (SERCA) pump is responsible for bringing Ca2+from the cytosol into its storage site, the sarcoplasmic reticulum (SR), at the expense of ATP. We have recently demonstrated that, in the soleus of spaceflown mice, the Ca2+uptake ability of the SERCA pump is severely impaired and this may be attributed to increases in reactive oxygen/nitrogen species (RONS), to which SERCA is highly susceptible. The purpose of this study was therefore to investigate whether treatment with the antioxidant, MnTnBuOE-2-PyP (BuOE), could attenuate muscle atrophy and SERCA dysfunction. We received soleus muscles from the rodent research 18 mission which had male mice housed on the international space station for 35 days and treated with either saline or BuOE. Spaceflight significantly reduced the soleus:body mass ratio and significantly increased SERCA’s ionophore ratio, a measure of SR Ca2+leak, and 4-HNE content (marker of RONS), none of which could be rescued by BuOE treatment. In conclusion, we find that spaceflight induces significant soleus muscle atrophy and SR Ca2+leak that cannot be counteracted with antioxidant treatment. Future work should investigate alternative therapeutics that are specifically aimed at increasing SERCA activation or reducing Ca2+leak.

Highlights

Spaceflight induces soleus muscle atrophy and increases SR Ca2+leak

Treatment with the antioxidant, BuOE, was unable to attenuate the detrimental effects of spaceflight on the soleus muscle

Future work should investigate the potential benefits of SERCA activation or reducing SR Ca2+leak
From Planning Stage To FAIR Data: A Practical Metadatasheet For Biomedical Scientists
Authors: Seep Lea , Grein Stephan , Splichalova Iva , Ran Danli , Mikhael Mickel , Hildebrand Staffan , Lauterbach Mario , Hiller Karsten , Silva Ribeiro Dalila Juliana , Sieckmann Katharina , Kardinal Ronja , Huang Hao , Yu Jiangyan , Kallabis Sebastian , Behrens Janina , Till Andreas , Peeva Viktoriya , Strohmeyer Akim , Bruder Johanna , Blum Tobias , Soriano-Arroquia Ana , Tischer Dominik , Kuellmer Katharina , Li Yuanfang , Beyer Marc , Gellner Anne-Kathrin , Fromme Tobias , Wackerhage Henning , Klingenspor Martin , Fenske Wiebke K. , Scheja Ludger , Meissner Felix , Schlitzer Andreas , Mass Elvira , Wachten Dagmar , Latz Eicke , Pfeifer Alexander , Hasenauer Jan
Published: January 2024

Datasets consist of measurement data and metadata. Metadata provides context, essential for understanding and (re-)using data. Various metadata standards exist for different methods, systems and contexts. However, relevant information resides at differing stages across the data-lifecycle. Often, this information is defined and standardized only at publication stage, which can lead to data loss and workload increase.

In this study, we developed Metadatasheet, a metadata standard based on interviews with members of two biomedical consortia and systematic screening of data repositories. It aligns with the data-lifecycle allowing synchronous metadata recording within Microsoft Excel, a widespread data recording software. Additionally, we provide an implementation, the Metadata Workbook, that offers user-friendly features like automation, dynamic adaption, metadata integrity checks, and export options for various metadata standards.

By design and due to its extensive documentation, the proposed metadata standard simplifies recording and structuring of metadata for biomedical scientists, promoting practicality and convenience in data management. This framework can accelerate scientific progress by enhancing collaboration and knowledge transfer throughout the intermediate steps of data creation.
Embedding biomimetic vascular networks via coaxial sacrificial writing into functional tissue
Authors: Stankey Paul P. , Kroll Katharina T. , Ainscough Alexander J. , Reynolds Daniel S. , Elamine Alexander , Fichtenkort Ben T. , Uzel Sebastien G.M. , Lewis Jennifer A.
Published: January 2024

Printing human tissue constructs replete with biomimetic vascular networks is of growing interest for tissue and organ engineering. While it is now possible to embed perfusable channels within acellular and densely cellular matrices, they lack either the branching or multilayer architecture of native vessels. Here, we report a generalizable method for printing hierarchical branching vascular networks within soft and living matrices. We embed biomimetic vessels into granular hydrogel matrices via coaxial embedded printing (co-EMB3DP) as well as into bulk cardiac tissues via coaxial sacrificial writing into functional tissues (co-SWIFT). Each method relies on an extended core-shell printhead that promote facile interconnections between printed branching vessels. Though careful optimization of multiple core-shell inks and matrices, we show that embedded biomimetic vessels can be coaxially printed, which possess a smooth muscle cell-laden shell that surrounds perfusable lumens. Upon seeding these vessels with a confluent layer of endothelial cells, they exhibit good barrier function. As a final demonstration, we construct biomimetic vascularized cardiac tissues composed of a densely cellular matrix of cardiac spheroids derived from human induced pluripotent stem cells. Importantly, these co-SWIFT cardiac tissues mature under perfusion, beat synchronously, and exhibit a cardio-effective drug response in vitro. This advance opens new avenues for the scalable biomanufacturing of organ-specific tissues for drug testing, disease modeling, and therapeutic use.
Ordered and disordered regions of the Origin Recognition Complex (ORC) combine to direct in-vivo binding at symmetric and non-symmetric motif sequences
Authors: Chappleboim Michal , Naveh-Tassa Segev , Carmi Miri , Levy Yaakov , Barkai Naama
Published: January 2024

The Origin Recognition Complex (ORC) seeds replication-fork formation by binding to DNA replication origins, which in budding yeast contain a 17bp DNA motif. High resolution structure of the ORC-DNA complex revealed two base-interacting elements: a disordered basic patch (Orc1-BP4) and an insertion helix (Orc4-IH). To define the ORC elements guiding its DNA bindingin-vivo, we mapped genomic locations of 38 designed ORC mutants, revealing that different ORC elements guide binding at different sites. At silencing-associated sites lacking the motif, ORC binding and activity were fully explained by a BAH domain. Within replication origins, we reveal two dominating motif variants showing differential binding modes and symmetry: an asymmetric motif whose binding requires Orc1-BP4 and Orc4-IH, and a symmetric one where another basic patch, Orc1-BP3, can replace Orc4-IH. Disordered basic patches are therefore key for ORC-motif bindingin-vivo, and we discuss how these conserved, minor-groove interacting elements can guide specific ORC-DNA recognition.
Serological Survey in a university community after the fourth wave of COVID-19 in Senegal
Authors: Thiam Fatou , Diouara Abou Abdallah Malick , Ndiaye Clemence Stephanie Chloe Anoumba , Diouf Ibrahima , Kebe Khadim , Senghor Assane , Djoumoi Djibaba , Mbaye Mame Ndew , Diop Idy , Sane Sarbanding , Coundoul Seynabou , Tene Sophie deli , Diop Mamadou , Dieng Abdou Lahat , Ndiaye Mamadou , Sall Saidou Moustapha , Diouf Massamba , Nguer Cheikh Momar
Published: January 2024

Cross-sectional survey was conducted to assess the true extent of COVID-19 exposure among students and staff of Polytechnic High School (PHS). Random cluster sampling was carried out between May 19 and August 18, 2022, after the fourth wave of COVID-19 transmission. IgM and IgG SARS-CoV-2 antibodies were screened using WANTAI SARS-CoV-2 ELISA assays. Seroprevalence and descriptive statistics were calculated. Moreover, the associations between seropositivity and different factors (age, gender, preventive, etc.) were determined using logistic regression. A total of 637 participants were recruited, including 563 students, followed by 52 TAS officers, and 22 professors. The median age among was 21 years [18–63]. 62.0% of the participants were female, and 36.89% were male, with a male-to-female ratio = 0.59. The overall IgG and IgM seroprevalence were 92% and 6.91% respectively. We found a higher IgM seroprevalence in men than women (9.4% vs. 5.6%) and a lower IgM seroprevalence in (18-25) age group compared to (55-65) years. Low compliance with preventive measures was found with a significant IgM seroprevalence depending on non-respect of social distancing (p = 0.008). IgM seropositivity was associated with Body Mass Indice (BMI) categorized (O.R. 0.238,p= 0.043), ethnic group (O.R. 0.723,p= 0.046) and marital status (O.R. 2.399,p= 0.021). Moreover, IgG seropositivity was associated with vaccination status (O.R. 4.741,p< 0.001). Our study revealed that the majority of students and staff have already been exposed to SARS-CoV-2, which confirms the circulation of SARS-CoV-2 in PHS at the time of the survey. Our results underline the importance of seroepidemiological surveys to estimate the real impact of the COVID-19 pandemic in a community and to monitor disparities in antibody response in the population.
Towards the identification of the molecular toolkit involved in scale worm bioluminescence (Polinoidae, Annelida)
Authors: Gracia-Sancha Carlota , Conejero María , Taboada Sergio , Martín Daniel , Riesgo Ana , Holford Mandë , Verdes Aida
Published: January 2024

Background

Bioluminescence, or the ability of a living organism to produce light, has evolved independently in numerous taxa inhabiting a panoply of ecosystems, although it is more frequent among marine animals. Scale worms are a group of marine polynoid annelids characterized by having dorsal scales, known as elytra, capable of emitting bioluminescent light by a mostly unknown molecular mechanism that may involve a photoprotein called polynoidin. Here, we used RNA-seq data to characterize the expression of genes potentially involved in light production in the polynoid speciesHarmothoe imbricata(Linnaeus, 1767) andHarmothoe areolata(Grube, 1860) across tissues of the specimens. We also compared the transcriptomes of the selected species with other bioluminescent and non-bioluminescent polynoids, to identify shared orthologous genes potentially involved in light production. In addition, we investigated the disposition of the photocytes on the elytra using confocal microscopy and histological analyses.

Results

Our results showed a total of 16 candidate genes, 15 orthologous genes and 12 enriched GO terms potentially involved in bioluminescence, including genes related with oxidative stress, cytoskeleton, nervous system, stress response, wounding response, eye constituents and metabolic pathways. We also confirmed the presence of photocytes in both species, which appeared distributed around the elytrophore.

Conclusions

Among the genes found potentially implicated in bioluminescence we suggest that the oxidoreductase protein, peroxidasin, could be a polynoidin candidate since it appears overexpressed in the elytra of both species and it is located in the endoplasmic reticulum, where this photoprotein has been described to be found.
Sequence-function mapping of proline-rich antimicrobial peptides
Authors: Collins Jonathan , McConnell Adam , Schmitz Zachary D. , Hackel Benjamin J.
Published: January 2024

Antimicrobial peptides (AMPs) are essential elements of natural cellular combat and candidates as antibiotic therapy. Elevated function may be needed for robust physiological performance. Yet, both pure protein design and combinatorial library discovery are hindered by the complexity of antimicrobial activity. We applied a recently developed high-throughput technique, sequence-activity mapping of AMPs via depletion (SAMP-Dep), to proline-rich AMPs. Robust self-inhibition was achieved for metalnikowin 1 (Met) and apidaecin 1b (Api). SAMP-Dep exhibited high reproducibility with correlation coefficients 0.90 and 0.92, for Met and Api, respectively, between replicates and 0.99 and 0.96 for synonymous genetic variants. Sequence-activity maps were obtained via characterization of 26,000 and 34,000 mutants of Met and Api, respectively. Both AMPs exhibit similar mutational profiles including beneficial mutations at one terminus, the C-terminus for Met and N-terminus for Api, which is consistent with their opposite binding orientations in the ribosome. While Met and Api reside with the family of proline-rich AMPs, different proline sites exhibit substantially different mutational tolerance. Within the PRP motif, proline mutation eliminates activity, whereas non-PRP prolines readily tolerate mutation. Homologous mutations are more tolerated, particularly at alternating sites on one ‘face’ of the peptide. Important and consistent epistasis was observed following the PRP domain within the segment that extends into the ribosomal exit tunnel for both peptides. Variants identified from the SAMP-Dep platform were produced and exposed toward Gram-negative species exogenously, showing either increased potency or specificity for strains tested. In addition to mapping sequence-activity space for fundamental insight and therapeutic engineering, the results advance the robustness of the SAMP-Dep platform for activity characterization.
On the role of urban tropical tree collections in carbon allocation: expanding their functions beyond cultural and biodiversity conservation
Authors: Echeverri-Salazar Edwin , Villegas Juan Camilo , Alviar-Ramírez Lía Isabel , Mora Edwin Andrés
Published: January 2024

Trees support key processes in both natural and managed ecosystems. In highly intervened urban environments, trees have been generally associated with benefits such as air quality, microclimate regulation, and biodiversity conservation. University campuses contain diverse and well-managed tree collections that provide local functions such as education, conservation, research, and landscaping. However, little has been discussed about these collections in the general urban setting and how they relate to other urban ecosystem processes, such as carbon cycling. This is particularly evident in tropical regions where no current urban forest carbon sequestration estimations are available. In this work, we present the results of a pilot estimation of the carbon storage function of the university tree collection at the Universidad de Antioquia (Medellín, Colombia) through a bounding calculation that combines tree inventory data and allometric equations. Our results show that, on average, the university tree collection (including palms) sequesters 3.4 Mg C/ha/year (4.2x10−2Mg C/tree/year). Remarkably, our results are comparable to natural tropical forests, particularly in locations with similar climatic and biophysical conditions. When compared to other urban studies, our estimation ranges between 1.2-20.8 times larger than cities and other urban areas with similar estimations. We present a novel integrative method for estimating carbon storage and sequestration that can be widely applied in information-limited tropical contexts. We discuss how management practices of these urban forests contribute to improving their capacity to store carbon more efficiently and effectively participate in other urban ecosystem processes that derive benefits to society. More generally, our results highlight the role of universities and other similar urban tree collections (i.e. botanical gardens and urban parks) in local and regional ecosystem functions and their potential contribution to global carbon cycling.
Modulation of locomotion and motor neuron response by the cohesive effect of acute and chronic feeding states and acute d-amphetamine treatment in zebrafish larvae
Authors: Bansal Pushkar , Roitman Mitchell F. , Jung Erica E.
Published: January 2024

Amphetamine (AMPH) increases locomotor activities in animals, and the locomotor response to AMPH is further modulated by caloric deficits such as food deprivation and restriction. The increment in locomotor activity regulated by AMPH-caloric deficit concomitance can be further modulated by varying feeding schedules (e.g. acute and chronic food deprivation and acute feeding after chronic food deprivation). However, the effects of different feeding schedules on AMPH-induced locomotor activity are yet to be explicated. Here, we have explored the stimulatory responses of acutely administered d-amphetamine in locomotion under systematically varying feeding states (fed/sated and food deprivation) and schedules (chronic and acute) in zebrafish larvae. We used wild-type and transgenic[Tg(mnx1:GCaMP5)] zebrafish larvae and measured swimming activity and spinal motor neuron activityin vivoin real-time in time-elapsed and cumulative manner pre- and post-AMPH treatment. Our results showed that locomotion and motor neuron activity increased in both chronic and acute food deprivation post-AMPH treatment cumulatively. A steady increase in locomotion was observed in acute food-deprivation compared to an immediate abrupt increase in chronic food-deprivation state. The ad libitum-fed larvae exhibited a moderate increase both in locomotion and motor neuron activity. Conversely to all other caloric states, food-sated (acute feeding after chronic food deprivation) larvae moved moderately less and exhibited a mild decrease in motor neuron activity after AMPH treatment. These results point to the importance of the feeding schedule in modulating amphetamine’s characteristic stimulatory response on behavior and motor neurons.
Characterization of the placenta-specific EnvV2-Fca soluble protein derived from endogenous retrovirus
Authors: Pramono Didik , Sugimoto Kenji , Kimura Tohru , Miyake Ariko , Nishigaki Kazuo
Published: January 2024

Endogenous retroviruses (ERVs) are remnants of ancestral viruses in the host genome. Here, we identified the expression of a defective retroviralenvgene belonging to the ERV group V member 2 Env (EnvV2) inFelis catus(EnvV2-Fca), which was specifically detected in the placental trophoblast syncytiotrophobic layer. EnV2-Fca was expressed as a secreted protein in cultured cells. Genetic analyses indicated that EnvV2 genes are widely present in vertebrate, and are under purifying selection among carnivores, suggesting a potential benefit for the host. Notably, this study suggests that birds, bats, and rodents carrying EnvV2 may play significant roles as intermediate vectors in spreading or cross-transmitting viruses among species. Overall, our findings provide valuable insights into the evolution of ERV in vertebrate hosts.
Laboratory evaluation of the regeneration time, efficacy and wash-resistance of PermaNet® Dual (a deltamethrin-chlorfenapyr net) against susceptible and pyrethroid-resistant strains ofAnopheles gambiae
Authors: Syme Thomas , N’dombidjé Boris , Todjinou Damien , Ariori Victoria , Ngufor Corine
Published: January 2024

Pyrethroid-chlorfenapyr nets have been recommended for malaria control by the World Health Organisation (WHO) after an alpha-cypermethrin-chlorfenapyr net showed improved impact in epidemiological trials. PermaNet® Dual is a new deltamethrin-chlorfenapyr net developed by Vestergaard Sàrl to expand options to control programmes. We performed a series of laboratory studies according to WHO guidelines to assess the regeneration time, efficacy and wash-resistance of PermaNet® Dual. Regeneration time was determined by subjecting net pieces to cone bioassays and tunnel tests before and 0, 1, 2, 3, 5 and 7 days after washing. The wash-resistance of PermaNet® Dual was evaluated compared to WHO-prequalified pyrethroid-only (PermaNet® 2.0) and pyrethroid-chlorfenapyr (Interceptor® G2) nets by testing net pieces washed 0, 1, 3, 5, 10, 15 and 20 times in cone bioassays and tunnel tests. Tests were performed with susceptible and pyrethroid-resistant strains ofAnopheles gambiaeto separately assess the pyrethroid and chlorfenapyr components. Net pieces were also analysed to determine insecticide content. In regeneration time studies, the biological activity of the deltamethrin and chlorfenapyr components of PermaNet® Dual regenerated within 1 day after washing and a 1-day washing interval was adopted for wash-resistance studies. PermaNet® Dual induced high mortality (98%) and blood-feeding inhibition (98%) of the susceptible strain after 20 washes fulfilling WHO efficacy criteria in tunnel tests (≥80% mortality, ≥90% blood-feeding inhibition). Similar results were obtained with PermaNet® 2.0 (99% mortality, 99% blood-feeding inhibition) and Interceptor® G2 (99% mortality, 98% blood-feeding inhibition) washed 20 times. In wash-resistance tunnel tests against the pyrethroid-resistant strain, PermaNet® Dual washed 20 times induced high mortality (91%) and blood-feeding inhibition (73%) which was similar to Interceptor® G2 (87% mortality, 79% blood-feeding inhibition) and superior to PermaNet® 2.0 (47% mortality, 68% blood-feeding inhibition). PermaNet® Dual fulfilled WHO efficacy criteria in laboratory bioassays and showed potential to improve control of pyrethroid-resistant malaria vectors.
Development and Validation of The Activity-Based Checks (ABCs) of Pain: A Functional Pain Scale
Authors: Virgen Celina G. , Wright Robert , Renslo Bryan , Sawaf Tuleen , Moradi Hanna , Edelen Maria , Villwock Jennifer
Published: January 2024

The Activity-Based-Checks of Pain (ABCs) is a pain assessment tool incorporating activities of daily living and instrumental activities of daily living. Unlike widely used pain scales which are oftentimes unidimensional and highly subjective, the ABCs was designed to focus on function capabilities and limitations of patients due to pain. This study sought out to validate the factorial structure of the ABCs and assess its use in participants with chronic pain. Participants were recruited in two phases from Prolific – an online service designed to identify research participant recruitment based on study criteria. Phase one optimized the design of the ABCs, with 297 subjects selecting their preferred icon for each function and rating its understandability. The most preferred and understandable icons were then used in phase two, where 304 chronic pain participants completed the ABCs, PROMIS-29, additional PROMIS items that were analogous to the ABCs functions but not represented in the PROMIS-29, and the Brief Pain Inventory (BPI). Data was analyzed using exploratory factor analysis and confirmatory factor analysis demonstrating four factor loadings: multi-planal activities, sitting/hip flexor pain, walking/ambulation, and pain interference with lightweight unilateral activities. High internal consistency was demonstrated with all four factor loadings. Correlations between items in the ABCs, PROMIS, and BPI resulted in moderate to strong correlations demonstrating strong evidence for the validity of the ABCs as a functional pain assessment tool.
Use of Noisy Labels as Weak Learners to Identify Incompletely Ascertainable Outcomes: A Feasibility Study with Opioid-Induced Respiratory Depression
Authors: Jeffery Alvin D. , Fabbri Daniel , Reeves Ruth M. , Matheny Michael E.
Published: January 2024

Objective

Assigning outcome labels to large observational data sets in a timely and accurate manner, particularly when outcomes are rare or not directly ascertainable, remains a significant challenge within biomedical informatics. We examined whether noisy labels generated from subject matter experts’ heuristics using heterogenous data types within a data programming paradigm could provide outcomes labels to a large, observational data set. We chose the clinical condition of opioid-induced respiratory depression for our use case because it is rare, has no administrative codes to easily identify the condition, and typically requires at least some unstructured text to ascertain its presence.

Materials and Methods

Using de-identified electronic health records of 52,861 post-operative encounters, we applied a data programming paradigm (implemented in the Snorkel software) for the development of a machine learning classifier for opioid-induced respiratory depression. Our approach included subject matter experts creating 14 labeling functions that served as noisy labels for developing a probabilistic Generative model. We used probabilistic labels from the Generative model as outcome labels for training a Discriminative model on the source data. We evaluated performance of the Discriminative model with a hold-out test set of 599 independently-reviewed patient records.

Results

The final Discriminative classification model achieved an accuracy of 0.977, an F1 score of 0.417, a sensitivity of 1.0, and an AUC of 0.988 in the hold-out test set with a prevalence of 0.83% (5/599).

Discussion

All of the confirmed Cases were identified by the classifier. For rare outcomes, this finding is encouraging because it reduces the number of manual reviews needed by excluding visits/patients with low probabilities.

Conclusion

Application of a data programming paradigm with expert-informed labeling functions might have utility for phenotyping clinical phenomena that are not easily ascertainable from highly-structured data.
Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory
Authors: Feierman Emily R. , Louzon Sean , Prescott Nicholas A. , Biaco Tracy , Gao Qingzeng , Qiu Qi , Choi Kyuhyun , Palozola Katherine C. , Voss Anna J. , Mehta Shreya D. , Quaye Camille N. , Lynch Katherine T. , Fuccillo Marc V. , Wu Hao , David Yael , Korb Erica
Published: January 2024

Regulation of histone proteins affects gene expression through multiple mechanisms including exchange with histone variants. However, widely expressed variants of H2B remain elusive. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. We applied new tools including novel antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE, and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Lastly, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a novel mechanism linking histone variants to chromatin regulation, neuronal function, and memory. This work further identifies the first widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.
ListPred: A predictive ML tool for virulence potential and disinfectant tolerance inListeria monocytogenes
Authors: Gmeiner Alexander , Ivanova Mirena , Kaas Rolf Sommer , Xiao Yinghua , Otani Saria , Leekitcharoenphon Pimlapas
Published: January 2024

Despite current surveillance and sanitation strategies, foodborne pathogens continue to threaten the food industry and public health. Whole genome sequencing (WGS) has reached an unprecedented resolution to analyse and compare pathogenic bacterial isolates. The increased resolution significantly enhances the possibility of tracing transmission routes and contamination sources of foodborne pathogens. In addition, machine learning (ML) on WGS data has shown promising applications for predicting important microbial traits such as virulence, growth potential, and resistance to antimicrobials. Many regulatory agencies have already adapted WGS and ML methods. However, the food industry hasn’t followed a similarly enthusiastic implementation. Some possible reasons for this might be the lack of computational resources and limited expertise to analyse WGS and ML data and interpret the results. Here, we present ListPred, a ML tool to analyse WGS data ofListeria monocytogenes, a very concerning foodborne pathogen. ListPred is able to predict two important bacterial traits, namely virulence potential and disinfectant tolerance, and only requires limited computational resources and practically no bioinformatic expertise, which is essential for a broad application in the food industry.

AUTHOR SUMMARY

The contamination of food products with microbes such as pathogenic bacteria is a big concern for the food industry. The rapid detection, characterisation and eradication of microbial contaminants are of utmost importance to ensure safe food products. Fortunately, strict food safety regulations and stringent cleaning protocols prevent the transmission of harmful bacteria to humans. Individual bacteria of the same species can have varying abilities to resist cleaning agents or infect a host, meaning that some pathogen isolates might be more dangerous than others. Novel techniques such as genome sequencing and machine learning can help to determine such differences in individual bacteria. Unfortunately, these techniques require a lot of computational power and expertise that is limited in the food industry. This is why we developed an easy-to-use software tool called ListPred that can be used with few computational requirements and little expertise. ListPred helps food companies to answer two essential questions: how dangerous areListeria monocytogenespathogens, and how to get rid of them most efficiently?
Wild Patagonian yeast improve the evolutionary potential of novel interspecific hybrid strains for Lager brewing
Authors: Molinet Jennifer , Navarrete Juan P. , Villarroel Carlos A. , Villarreal Pablo , Sandoval Felipe I. , Nespolo Roberto F. , Stelkens Rike , Cubillos Francisco A.
Published: January 2024

ABSTRACT

Lager yeasts are limited to a few strains worldwide, imposing restrictions on flavour and aroma diversity and hindering our understanding of the complex evolutionary mechanisms during yeast domestication. The recent finding of diverseS. eubayanuslineages from Patagonia offers potential for generating new Lager yeasts and obtaining insights into the domestication process. Here, we leverage the natural genetic diversity ofS. eubayanusand expand the Lager yeast repertoire by including three distinct PatagonianS. eubayanuslineages. We used experimental evolution and selection on desirable traits to enhance the fermentation profiles of novelS. cerevisiaexS. eubayanushybrids. Our analyses reveal an intricate interplay of pre-existing diversity, selection on species-specific mitochondria,de-novomutations, and gene copy variations in sugar metabolism genes, resulting in high ethanol production and unique aroma profiles. Hybrids withS. eubayanusmitochondria exhibited greater evolutionary potential and superior fitness post-evolution, analogous to commercial Lager hybrids. Using genome-wide screens of the parental subgenomes, we identified genetic changes inIRA2,SNF3,IMA1andMALXgenes that influence maltose metabolism, and increase glycolytic flux and sugar consumption in the evolved hybrids. Functional validation and transcriptome analyses confirmed increased maltose-related gene expression, influencing grater maltotriose consumption in evolved hybrids. This study demonstrates the potential for generating industrially viable Lager yeast hybrids from wild Patagonian strains. Our hybridization, evolution, and mitochondrial selection approach produced hybrids with high fermentation capacity, expands Lager beer brewing options, and deepens our knowledge of Lager yeast domestication.
graded-CRISPRi, a novel tool for tuning the strengths of CRISPRi-mediated knockdowns inVibrio natriegensusing gRNA libraries
Authors: Stukenberg Daniel , Faber Anna , Becker Anke
Published: January 2024

In recent years, the fast-growing bacteriumVibrio natriegenshas gained increasing attention as it has the potential to become a next-generation chassis for Synthetic Biology. A wide range of genetic parts and genome engineering methods have already been developed. However, there is still a need for a well-characterized tool to effectively and gradually reduce the expression level of native genes. To bridge this gap, we created graded-CRISPRi, a system utilizing gRNA variants that lead to varying levels of repression strength. By incorporating multiple gRNA sequences into our design, we successfully extended this concept to simultaneously repress four distinct reporter genes. Furthermore, we demonstrated the capability of using graded-CRISPRi to target native genes, thereby examining the effect of various knockdown levels on growth.
Mathematical model of replication-mutation dynamics in coronaviruses
Authors: Blyuss K.B. , Kyrychko Y.N.
Published: January 2024

RNA viruses are known for their fascinating evolutionary dynamics, characterised by high mutation rates, fast replication, and ability to form quasispecies - clouds of genetically related mutants. Fast replication in RNA viruses is achieved by a very fast but error-prone RNA-dependent RNA polymerase (RdRP). High mutation rates are a double-edged sword: they provide RNA viruses with a mechanism of fast adaptation to a changing environment or host immune system, but at the same time they pose risk to virus survivability in terms of virus mutating beyond its error threshold. Coronaviruses, being a subset of RNA viruses, are unique in having a special enzyme, exoribonuclease (ExoN), responsible for proofreading and correcting errors induced by the RdRP. In this paper we consider replication dynamics of coronaviruses with account for mutations that can be neutral, deleterious or lethal, as well as ExoN. Special attention is paid to different virus replication modes that are known to be crucial for controlling the dynamics of virus populations. We analyse extinction, mutant-only and quasispecies steady states, and study their stability in terms of different parameters, identifying regimes of error catastrophe and lethal mutagenesis. With coronaviruses being responsible for some of the largest pandemics in the last twenty years, we also model the effects of antiviral treatment with various replication inhibitors and mutagenic drugs.
The EGF/EGFR-YAP1/TEAD2 axis-mediated BRAF inhibitor vemurafenib resistance upregulates STIM1 in melanoma
Authors: Bai Weiyu , Yan Chenghao , Yang Yichen , Sang Lei , Hao Qinggang , Yao Xinyi , Yu Jia , Wang Yifan , Li Xiaowen , Meng Mingyao , Yang Jilong , Shen Junling , Sun Yan , Sun Jianwei
Published: January 2024

STIM1 is the endoplasmic reticulum (ER) Ca2+sensor for store-operated entry (SOCE) and closely correlated to carcinogenesis and tumor progression. Previously we found that STIM1 is upregulated in melanoma cells resistant to the BRAF inhibitor vemurafenib, but the regulation mechanism is unknown. Here, we show that vemurafenib resistance upregulates STIM1 through an EGF/EGFR-YAP1/TEAD2 axis. Vemurafenib resistance can lead to the increase of EGF and EGFR levels to activate the EGFR signaling pathway. Reactivated EGFR signal promotes YAP1 nuclear localization to increase the expression of STIM1. Our finding not only demonstrates the mechanism by which vemurafenib resistance promotes STIM1 expression, but also provides combined targeting EGF/EGFR-YAP1/TEAD2-STIM1 to improve the therapeutic efficiency of BRAF inhibitor in melanoma patients.
Understanding species-specific and conserved RNA-protein interactionsin vivoandin vitro
Authors: Harris Sarah E. , Alexis Maria S. , Giri Gilbert , Cavazos Francisco F. , Murn Jernej , Aleman Maria M. , Burge Christopher B. , Dominguez Daniel
Published: January 2024

While evolution is often considered from a DNA- and protein-centric view, RNA-based regulation can also impact gene expression and protein sequences. Here we examined interspecies differences in RNA-protein interactions using the conserved neuronal RNA binding protein, Unkempt (UNK) as model. We find that roughly half of mRNAs bound in human are also bound in mouse. Unexpectedly, even when transcript-level binding was conserved across species differential motif usage was prevalent. To understand the biochemical basis of UNK-RNA interactions, we reconstituted the human and mouse UNK-RNA interactomes using a high-throughput biochemical assay. We uncover detailed features driving binding, show thatin vivopatterns are capturedin vitro, find that highly conserved sites are the strongest bound, and associate binding strength with downstream regulation. Furthermore, subtle sequence differences surrounding motifs are key determinants of species-specific binding. We highlight the complex features driving protein-RNA interactions and how these evolve to confer species-specific regulation.
Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders
Authors: Carbonell-Roig Josep , Aaltonen Alina , Cartocci Veronica , McGuirt Avery , Mosharov Eugene , Kehr Jan , Lieberman Ori J. , Sulzer David , Borgkvist Anders , Santini Emanuela
Published: January 2024

Autism Spectrum Disorders (ASD) consist of diverse neurodevelopmental conditions where core behavioral symptoms are critical for diagnosis. Altered dopamine neurotransmission in the striatum has been suggested to contribute to the behavioral features of ASD. Here, we examine dopamine neurotransmission in a mouse model of ASD characterized by elevated expression of the eukaryotic initiation factor 4E (eIF4E), a key regulator of cap-dependent translation, using a comprehensive approach that encompasses genetics, behavior, synaptic physiology, and imaging. The results indicate that increased eIF4E expression leads to behavioral inflexibility and impaired striatal dopamine release. The loss of normal dopamine neurotransmission is due to a defective nicotinic receptor signaling that regulates calcium dynamics in dopaminergic axons. These findings reveal an intricate interplay between eIF4E, DA neurotransmission, and behavioral flexibility, provide a mechanistic understanding of ASD symptoms and offer a foundation for targeted therapeutic interventions.