bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimentally quantifying impact of herbivory on duckweed communities in natural pond ecosystems
Authors: Subramanian Swapna K. , Turcotte Martin M.
Published: August 2023

Plant herbivory structures communities, impacts energy and nutrient flow in ecosystems, and drives speciation. Yet, our knowledge of plant-herbivore interactions remains limited in freshwater ecosystems compared to terrestrial ones. We still lack robust experimental data on the impact of herbivores in nature on whole families of important macrophytes such as the globally distributed duckweed family (Lemnaceae). We conducted a replicated manipulative field experiment, using exclosures, across multiple bodies of water quantifying both ambient herbivory as well as herbivory caused by the addition of two different weevil and aphid herbivores. We found that invertebrate herbivores can strongly impact duckweed multi-generational population growth (e.g., reducing daily relative growth rate by up to 82% compared to controls) and differentially impact duckweed species composition. These impacts, however, vary greatly across sites and with the identity of the herbivores. Our results suggest that insect herbivores can severely slow the growth of the of the world’s fastest growing plant family. It also provides crucial information as duckweed continue to be developed for various applied purposes such a biofuel production and bioremediation.
Island biogeography theory and the gut: why taller people tend to harbor more diverse gut microbiomes
Authors: Sarmiento Katherine Ramos , Carr Alex , Diener Christian , Locey Kenneth J. , Gibbons Sean M.
Published: August 2023

Prior work has shown a positive scaling relationship between vertebrate body size and gut microbiome alpha-diversity. This observation mirrors commonly observed species area relationships (SAR) in many other ecosystems. Here, we show a similar scaling relationship between human height and gut microbiome alpha-diversity across two large, independent cohorts, controlling for a wide range of relevant covariates, such as body mass index, age, sex, and bowel movement frequency. Island Biogeography Theory (IBT), which predicts that larger islands tend to harbor greater species diversity through neutral demographic processes, provides a simple mechanism for these positive SARs. Using an individual-based model of IBT adapted to the gut, we demonstrate that increasing the length of a flow-through ecosystem is associated with increased species diversity. We delve into the possible clinical implications of these SARs in the American Gut Cohort. Consistent with prior observations that lower alpha-diversity is a risk factor forClostridioides difficileinfection (CDI), we found that individuals who reported a history of CDI were shorter than those who did not and that this relationship appeared to be mediated by alpha-diversity. We also observed that vegetable consumption mitigated this risk increase, also by mediation through alpha-diversity. In summary, we find that body size and gut microbiome diversity show a robust positive association, that this macroecological scaling relationship is related to CDI risk, and that greater vegetable intake can mitigate this effect.
Quantitative evaluation of internal clustering validation indices using binary datasets
Authors: Pakgohar Naghmeh , Lengyel Attila , Botta-Dukát Zoltán
Published: August 2023

Different clustering methods often classify the same dataset differently. Selecting the ‘best’ clustering solution out of a multitude of alternatives is possible with cluster validation indices. The behavior of validity indices changes with the structure of the sample and the properties of the clustering algorithm. Unique properties of each index cause increasing or decreasing performance in some conditions. Due to the large variety of cluster validation indices, choosing the most suitable index concerning the dataset and clustering algorithms is challenging. We aim to assess different internal clustering validation indices. In the present paper, the validity indices consist of geometric and non-geometric methods. For this purpose, we applied simulated datasets with different noise levels. Each dataset was repeated 20 times. Three clustering algorithms with Jaccard dissimilarity are used, and 27 clustering validation indices are evaluated. The results provide a reliability guideline for the selection cluster validity indices.
CIRI-hub: an integrated and visual analytics platform for circular RNAs in cancers
Authors: Wu Wanying , Zhang Jinyang , Zhao Fangqing
Published: August 2023

Recent studies have demonstrated the emerging functions of circular RNAs (circRNAs) in regulating tumor progression and metastasis, and various databases have been established for exploring the expression patterns and features of circRNAs. However, all these databases only provide simple browsing or searching functions with a limited collection of samples, and none of them provides integrated analytical functions of given circRNAs or in-house RNA-Seq data. Here, we developed CIRI-hub, which provides a user-friendly webserver for integrative analyses of circRNAs and outputting publication-quality figures. CIRI-hub integrates a compendium of 2187 tumor and 680 normal RNA-seq libraries spanning 33 tissue types. The CIRI-hub webserver can accept various formats of input, and perform automated analysis of circRNAs in user input data as well as a variety of tumor and matching normal tissues. All analysis results can be downloaded as vectorized figures, and thresholds and plotting parameters can be interactively customized using the visual interface. We believe that CIRI-Hub will serve as a powerful tool for identifying novel cancer biomarkers and exploring the biological functions of circRNAs in tumorigenesis.

Key Points

CIRI-hub integrates a compendium of 2187 tumor and 680 normal RNA-seq libraries spanning 33 tissue types, and provides comprehensive analysis and visualization functions for pan-cancer circRNA analysis.

CIRI-hub permits users to specific circRNAs of their interests or upload their dataset and provides interactively customization of analysis algorithms and plotting parameters on the web interface.

CIRI-hub can serve as a powerful tool for identifying novel cancer biomarkers and exploring the biological functions of circRNAs in tumorigenesis.
Noninvasive focal transgene delivery with viral neuronal tracers in the marmoset monkey
Authors: Parks T. Vincenza , Szczupak Diego , Choi Sang-Ho , Schaeffer David J.
Published: August 2023

Although preclinical neuroscientific modeling species permit invasive intracranial delivery of targeted neurotropic agents, direct intracranial injections are not readily translatable to clinical therapeutics. Transcranial focused ultrasound (tFUS) has been identified as a technique to circumvent surgical injections altogether by transiently opening the blood-brain barrier (BBB) with selective focus. We have recently characterized the ability to focally deliver substances across the BBB in the marmoset, a non-human primate model with similar husbandry requirements to rodents but with cortical topologies more similar to humans. Here, we establish a reliable method for selectively delivering adeno-associated viral vectors (AAVs) across the BBB in marmoset frontal cortex with tFUS and demonstrate long-range anterograde neuronal tracing. Using a single-element 1.46 MHz transducer, we focally perturbed the BBB (∼1 x 2 mm) in area 8aD of frontal cortex in four adult marmoset monkeys using low-intensity focused ultrasound aided by microbubbles. We confirmed BBB opening via a gadolinium-enhanced MRI at 9.4 T prior to AAV delivery. Within an hour of opening the BBB, either AAV2 or AAV9 was delivered systemically via tail-vein injection. Four to six weeks later, animals were sacrificed, and microscopy was performed to confirm the presence of neurons transduced as indicated by EGFP or mCherry fluorescence. In all four marmosets, neurons were observed at the site of BBB perturbation, with AAV2 showing an exiguous distribution of transduced neurons when compared to AAV9. The results are compared to direct intracortical injections of anterograde tracers into area 8aD and similar (albeit sparser) long-range connectivity was observed. With evidence of transduced neurons specific to the region of BBB opening as well as long-distance tracing, we establish a framework for focal noninvasive transgene delivery to the marmoset brain. This technique will be of utility for the burgeoning marmoset model, with applications for noninvasive delivery of therapeutics, genetic delivery of precursors for techniques like two-photon imaging, or neuronal tracing across the lifespan.
Fractionating difficulty during sentence comprehension using functional neuroimaging
Authors: Thothathiri Malathi , Basnakova Jana , Lewis Ashley G. , Briand Josephine M.
Published: August 2023

Sentence comprehension is highly practiced and largely automatic, but this belies the complexity of the underlying processes. We used functional neuroimaging (fMRI) to investigate garden-path sentences that cause difficulty during comprehension, in order to unpack the different processes used to support sentence interpretation. By investigating garden-path and other types of sentences within the same individuals, we functionally profiled different regions within the temporal and frontal cortices in the left hemisphere. The results revealed that different aspects of comprehension difficulty are handled by left posterior temporal, left anterior temporal, ventral left frontal, and dorsal left frontal cortices. The functional profiles of these regions likely lie along a spectrum of specificity to generality, including language-specific processing of linguistic representations, more general conflict resolution processes operating over linguistic representations, and processes for handling difficulty in general. These findings suggest that difficulty is not unitary and that there is a role for a variety of linguistic and non-linguistic processes in supporting comprehension.
Uumarrty: Agent Based Simulation Model of Predator Prey Interactions with a Game Theoretical Framework
Authors: Remington Michael , Clark Rulon W. , Hanscom Ryan , Higham Timothy E. , Sukumaran Jeet
Published: August 2023

Evolutionary game theory boasts a rich history of application in the study of phenotypic evolution and behavioral strategies. Complementing this, agent-based modeling offers a powerful simulation framework that allows for explicit modeling and parameterization of individual agents within a virtual environment. The agent-based modelling approach empowers ecologists and evolutionary biologists to accurately model highly complex and dynamic systems. Leveraging these methodologies, we developed the agent-based model Uumarrty, which integrates concepts from game theory to investigate the evolution of behavioral phenotypes. Our model embraces essential game theoretical principles, including pay-offs, mixed versus pure strategies, and optimal behavioral strategies, seamlessly within the agent-based framework. Furthermore, we introduced a novel metric called the Nash score, which serves as an analog of the evolutionarily stable strategy within our agent-based environment. With this innovative approach, researchers gain a versatile tool to comprehensively explore optimal behavioral strategies and assess their evolutionary stability. To demonstrate the efficacy of our model, we applied it to a predator-prey system involving kangaroo rats and rattlesnakes. By examining various factors such as differing foraging gains by kangaroo rats, varying strike success of rattlesnakes by microhabitat, and the influence of introducing a second predator, we gained valuable insights into the evolution of microhabitat preferences within this predator-prey system.
Stellate Ganglion Block to Treat Long COVID-19 Syndrome, A 41 patient Retrospective Cohort Study
Authors: Pearson Lisa , Maina Alfred , Thompson Leah , Harden Sherri , Aaroe Abbey , Compratt Taylor
Published: August 2023

Post Covid-19 condition (PCC), long COVID-19 syndrome and post-acute sequelae of SARS-CoV-2 (PASC) all refer to a constellation of symptoms that are unresolved long after the acute phase of the viral infection. The severity of symptoms can vary from mild and tolerable to severe and debilitating.1,2Due to the evolving nature of the SARS-CoV-2 pandemic, treatment protocols for the illness are in a constant state of evolution. The early stage of long COVID-19 syndrome contributes to a dearth of treatment protocols based on empirical evidence, while the absence of a conclusive pathophysiological understanding further complicates the development of such protocols. Current treatment regimens include homeopathic medicine, specialist system focused treatments, infusion therapies, hyperbaric oxygenation, and polypharmacy. The physiological, psychological, and societal impact of long COVID-19 cannot be approached casually and must govern the intensity with which the healthcare community approaches treatment of long COVID-19 syndrome.

In this 41-patient cohort study from a chronic pain management practice, the use of either unilateral or bilateral stellate ganglion block (SGB) was explored to manage symptoms associated with long COVID-19 syndrome. Results indicated that a substantial proportion of patients (86%) experienced a reduction of their symptoms following SGB treatment.
Why mothers continue to die in Pakistan: a nested case-control study of predictors of maternal mortality
Authors: Ahmad Ahsan Maqbool , Shah Iqbal H. , Mir Ali Muhammad , Sadiq Maqsood , Bosan Muddassir Altaf
Published: August 2023

Background

Maternal mortality ratio (MMR) declined in Pakistan from 276 maternal deaths per 100,000 live births in 2006-07 to 186 (confidence interval: 138-234) in 2019. Despite this decline, reasons why mothers continue to die, the inequity in the burden of maternal mortality and its predictors largely remain unknown. We investigate the levels and predictors of maternal mortality in Pakistan.

Methods

The in-depth analysis of Pakistan Maternal Mortality Survey (PMMS) 2019 was undertaken using the nested case-control design. We matched 147 maternal deaths that occurred during three years prior to PMMS 2019, defined as “cases”, with 724 women who delivered during the same period, defined as “controls”. We compared socio-demographic background characteristics of cases and controls and performed multivariate regression to investigate the predictors of maternal mortality in Pakistan.

Results

Cases and controls were similar on access to antenatal care (ANC) and ANC provider, but differed on age, education, number of pregnancies, type of delivery, tetanus toxoid vaccination during last pregnancy, and ever using a contraceptive method. More of the cases had their last delivery by a skilled birth attendant (83% compared to 63% among controls) and delivered at the government hospital (43% compared to 33% among controls) while home delivery was relatively more common among controls (32% compared to 25% among cases). Odds of maternal death were lowest for women giving birth during age 20-29 (odds ratio – OR: 0.5; 95% CI 0.23-1.07) as compared to women in age 15-19 and those age 30-39 (OR: 1.34; 95% CI 0.61-2.95) and 40-49 (OR: 1.21; 95% CI 0.42-3.45), and among women with secondary or higher education (OR: 0.35; 95% CI 0.17-0.74) compared to women with no education. Surprisingly, women who had their delivery by a skilled birth attendant experienced higher odds of maternal death (OR: 4.07; 95% CI 2.19- 7.57) compared to those who did not. Whereas women having had tetanus injection during last pregnancy (OR: 0.1; 95% CI 0.0-0.96) and ever-used contraceptives (OR: 0.23; 95% CI 0.11-0.39) tend to have reduced odds of maternal death compared to women who did not have the injection and who never used contraceptives, respectively.

Conclusions

Women in certain sub-groups confront higher risks of maternal death. Increasing female education, preventing early and late childbearing through contraceptive use, increasing tetanus vaccination during pregnancy, improving providers’ skills, and quality of health care are required to eliminate preventable maternal deaths in Pakistan.
Scaling laws of human transcriptional activity
Authors: Hong Jiayin , Cavga Ayse Derya , Shah Devina , Laue Ernest , Taipale Jussi
Published: August 2023

Each human chromosome maintains its individuality during the cell cycle, and occupies a spatially limited volume, termed chromosome territory. Each linear chromosomal DNA is folded into multiple loops in the three dimensional space, and further organized into densely packed heterochromatin, less dense euchromatin and nucleosome-free regions that are accessible for transcription factor binding. As the average density of chromatin in the nucleus is very high, size exclusion potentially restricts access of large macromolecules such as RNA polymerase II and Mediator to DNA buried in chromosomal interiors. To examine this idea, we investigated whether increase in chromosome size leads to relative decrease in transcriptional activity of larger chromosomes. We found that the scaling of gene expression relative to chromosome size follows exactly the surface-area-to-volume ratio, suggesting that active genes are located at chromosomal surfaces. To directly test this hypothesis, we developed a scalable probe to assess chromatin accessibility to macromolecules of different sizes. We show that, at the chromosomal level, open chromatin landscapes of small and large molecules are strikingly similar. However, at a finer locus level, regions accessible to small transcription factors were primarily enriched around promoters, whereas regions accessible to large molecules were dispersed along gene bodies. Collectively, our results indicate that DNA accessibility is controlled at two different scales, and suggest that making chromatin accessible to large molecules is a critical step in the control of gene expression.
MetaCerberus: distributed highly parallelized scalable HMM-based implementation for robust functional annotation across the tree of life
Authors: Figueroa Jose L. , Dhungel Eliza , Brouwer Cory R. , White Richard Allen
Published: August 2023

MetaCerberus is an exclusive HMM/HMMER-based tool that is massively parallel, on low memory, and provides rapid scalable annotation for functional gene inference across genomes to metacommunities. It provides robust enumeration of functional genes and pathways across many current public databases including KEGG (KO), COGs, CAZy, FOAM, and viral specific databases (i.e., VOGs and PHROGs). In a direct comparison, MetaCerberus was twice as fast as EggNOG-Mapper, and produced better annotation of viruses, phages, and archaeal viruses than DRAM, PROKKA, or InterProScan. MetaCerberus annotates more KOs across domains when compared to DRAM, with a 186x smaller database and a third less memory. MetaCerberus is fully integrated with differential statistical tools (i.e., DESeq2 and edgeR), pathway enrichment (GAGE R), and Pathview R for quantitative elucidation of metabolic pathways. MetaCerberus implements the key to unlocking the biosphere across the tree of life at scale.

Availability and implementation

MetaCerberus is written in Python and distributed under a BSD-3 license. The source code of MetaCerberus is freely available athttps://github.com/raw-lab/metacerberus. Written in python 3 for both Linux and Mac OS X. MetaCerberus can also be easily installed using mamba create –n metacerberus –c bioconda –c conda-forge metacerberus
RNA binding limits the ligand induced transcriptional potential of estrogen receptor-alpha (ERα)
Authors: Soota Deepanshu , Saravanan Bharath , Mann Rajat , Kharbanda Tripti , Notani Dimple
Published: August 2023

Transcription factors (TFs) primarily regulate gene expression by binding to DNA through their DNA binding domains (DBD). Additionally, approximately half of these TFs also interact with RNA. However, the role of RNA in enabling TF binding on chromatin and subsequent transcription is poorly understood. Estrogen receptor-α (ERα) is one such TF that activates genes in response to estrogen stimulation. Here, we report that ERα interacts with various types of RNAs in ligand dependent manner via its RNA binding motif in hinge region. RNA binding defects lead to a global loss of ERα binding in the genome, particularly at weaker ERα motifs. In the absence of RNA binding, the ERα exhibits dynamic behavior in the nucleus and unexpectedly, the dynamic binding coincides with robust polymerase loading on ERα bound chromatin regions. The higher occupancy of PolII was recapitulated by robust ligand induced transcription of ERα-regulated genes. Collectively, our results suggest that RNA interactions strengthen ERα binding to chromatin limiting the ligand-dependent transcriptional upregulation of estrogen-induced genes.
Intracellular mechanical fingerprint reveals cell type specific mechanical tuning
Authors: Muenker Till M. , Vos Bart E. , Betz Timo
Published: August 2023

Living cells are complex entities that perform many different complex tasks with astonishing robustness. While the direct dependence of biological processes on controlled protein expression is well established, we only begin to understand how intracellular mechanical characteristics guide and support biological function. This is in stark contrast to the expected functional role that intracellular mechanical properties should have for many core cellular functions such as organization, homeostasis and transport. From a mechanical point of view, cells are complex viscoelastic materials that are continuously driven out of thermodynamic equilibrium, which makes both a physical measurement and mathematical modeling of its properties difficult. Here, we define a “mechanical fingerprint” that can not only characterize the intracellular mechanical state, but also carve out the mechanical differences between cell types with the potential to relate these to proper cell function. By analyzing the frequency-dependent viscoelastic properties and intracellular activity of cells using microrheology, we distilled the complex active mechanical state into just 6 parameters that comprise the mechanical fingerprint. The systematic investigation of the fingerprint illustrates a parameter tuning that can be explained by the functional cellular requirements. However, the full potential of the mechanical fingerprint is given by a statistical analysis of its parameters across all investigated cell types, which suggests that cells adjust mechanical parameters in a correlated way to position their intracellular mechanical properties within a well defined phase-space that is spanned between activity, mechanical resistance and fluidity. This paves the way for a systematic study of the interdependence of biological function and intracellular active mechanics.
Transferrin Receptor Targeting Chimeras (TransTACs) for Membrane Protein Degradation
Authors: Zhang Dingpeng , Duque-Jimenez Jhoely , Brixi Garyk , Facchinetti Francesco , Rhee Kaitlin , Feng William W. , Jänne Pasi A. , Zhou Xin
Published: August 2023

Cancer cells require high levels of iron for rapid proliferation, leading to a significant upregulation of the iron carrier protein Transferrin Receptor (TfR) on their cell surface. Leveraging this phenomenon and the exceptionally fast endocytosis rate of TfR, we introduce Transferrin Receptor TArgeting Chimeras (TransTAC), a novel molecular archetype for membrane protein degradation in cancers and other cell types. TransTACs repurpose the naturally recycling receptor TfR1 for protein degradation. To accomplish this, we utilized a combination of protein engineering strategies to redirect the target protein from recycling-endosome trafficking to lysosomal degradation. We show that TransTACs can highly efficiently degrade a diverse range of single-pass, multi-pass, native, or synthetic membrane proteins, establishing new possibilities for targeted cancer therapy.
Increased tolerance to commonly used antibiotics in aPseudomonas aeruginosa ex vivoporcine keratitis model
Authors: Okurowska K. , Monk P. N. , Karunakaran E.
Published: August 2023

Antibiotics in development are usually tested on rapidly dividing cells in a culture medium and do not reflect the complexity of infectionsin vivo, while testingin vivois limited, expensive and ethically concerning. This often results in the development and subsequent prescription of antibiotics only targeting infections in which pathogens are undergoing rapid cell division and in case of persistent infections like keratitis leads to poor clinical outcomes such as impaired vision or loss of an eye. In this study, we demonstrate antibiotic tolerance ofPseudomonas aeruginosastrains PA01 and PA14 using theex vivoporcine keratitis model in which bacterial physiology more closely mimics infectionsin vivothan in a culture medium.

MBEC and MIC were used as a guideline to establish the concentration of applied antibiotics on tissue. Infectedex vivoporcine corneas were treated with therapeutically relevant concentrations of gentamicin, ciprofloxacin and chloramphenicol. Ciprofloxacin was the most potent across all tests demonstrating a positive correlation with MIC but not MBEC. Nonetheless, the results demonstrated that MIC and MBEC concentrations were not sufficient to clear infection even after 18 hours of continuous exposure to the tested antibiotics reflecting the need for novel antibiotics that can target the persistent subpopulation of these pathogens and the ability of theex vivokeratitis model to be a relevant platform to identify novel antibiotics with suitable activities. There was a clear visual distinction between corneas infected with cytotoxic strain PA14 and invasive strain PA01. In this study, both strains PA14 and PA01 showed a high level of antibiotic tolerance, which suggests that in clinical settings the treatment approach could be similar regardless of the causative strain.

Data summary

The authors confirm all supporting data and protocols have been provided within the article or through supplementary data files.
Downstream effects of dre-miR-210-5p in zebrafish primary ovarian cell culture
Authors: van Gelderen T.A. , Ribas L.
Published: August 2023

MicroRNAs (miRNAs) are small, non-coding RNAs that are involved in post-transcriptional gene regulation in many cellular functions and are highly conserved throughout evolution. In teleost fish species, miRNAs are believed to play a role in the reproductive system, but more research is needed to better understand the functions of miRNAs in fish gonads. Furthermore, miR-210 has previously been described to be involved in many processes, such as hypoxia response, angiogenesis, cell proliferation and male infertility. The aim of this study was, first, to develop anin vitromodel in fish to study the functions of miRNAs and second, to identify target genes of dre-miR-210-5p by establishing a primary ovarian cell culture in zebrafish (Danio rerio). The cell culture was performed by isolating ovaries from adult female fish (n=4) which were incubated with dre-miR-210-5p mimic or scramble miRNA mimic. Cell survival was studied by flow cytometry analysis and fluorescent microscopy. Following, the effect of dre-miR-210-5p on ovarian cells was uncovered by RNA-sequencing, identifying ∼6,000 targeted-genes differentially expressed (DEGs), of which ∼2,600 downregulated and ∼3,400 upregulated. GO term and KEGG pathway analyses showed downregulated genes involved in cell cycle processes and reproduction-related pathways while, in contrast, immune-related pathways were upregulated after miR-210 mimic treatment in the ovarian cells. To provide the molecular mechanisms triggered by miRNA-210, seed regions of targeted genes were identified andin silicoanalysis classified DEGs as potential biomarkers in reproduction or immune cell types. These results support the crosstalk between the reproductive and immune system in which dre-miR-210-5p plays a key role in the transcriptomic alteration in the fish ovaries.

Take home message

miR-210 promotes the immune response and suppresses oocyte meiosis in the ovarian cells in zebrafish
Is it what’s inside that matters? A conserved microbiome in woody tissues ofPinus radiata
Authors: Daley Kaitlyn , Eslami Yeganeh , Armstrong Charlotte , Wigley Kathryn , Wakelin Steven A.
Published: August 2023

Understanding the interaction of endophytic microbiomes and their tree hosts may provide insights into wood formation and quality. Given the role of wood in carbon and nutrient cycling, this will provide valuable insights for forest growth and carbon cycling globally. Furthermore, the management of these interactions may add new value to wood-and fibre-based forest products. We assessed the microbiome of outer and inner bark, cambium tissue, year 2-8 wood increments, and the pith of 11Pinus radiatatrees, a widely planted, model conifer species. Diverse prokaryotic and fungal microbiomes were present in all trees, with communities structured by tissue type (p<0.001). Inner and outer bark tissues had high richness and the most distinct communities. Microbiome richness was lowest in year 2 through to year 8 wood, and the communities in these samples had similar composition. Prokaryote communities were dominated by Alpha-Beta-, and Gamma-proteobacteria, Actinobacteria, Firmicutes (Clostridia and Bacilli). Within fungal communities, Sordariomycetes comprised over 90% of the taxa present. Microbiomes of cambial and pith tissues were distinct to those niches. Overall, we provide further support that the wood of conifers is host to distinct microbiome communities. Microbiomes in these niches are profoundly placed to impact tree physiology, health, and fitness, through to ecosystem function and global carbon cycles.
Association of coffee consumption in metabolic syndrome: a cross-sectional and Mendelian randomization study in UK Biobank
Authors: Wong Tommy Hon Ting , Luo Shan , Au Yeung Shiu Lun , Louie Jimmy Chun Yu
Published: August 2023

Objective

To investigate the associations between coffee consumption and metabolic syndrome and its component conditions, as well as the effect of using milk, sugar, and artificial sweetener on these associations.

Research Design and Methods

The cross-sectional analysis included 351,805 participants from the UK Biobank. Coffee consumption data was obtained using food frequency questionnaire and 24-hour recall and metabolic syndrome was ascertained based on blood biochemistry results and self-reported medication use. Odds ratios were calculated using multivariable logistic regression adjusted for lifestyle and socioeconomic factors, with verification using two-sample Mendelian randomization.

Results

Coffee consumption up to 2 cups per day was inversely associated with metabolic syndrome (1 cup/day, OR: 0.88, 95% CI: 0.85, 0.92; 2 cups/day, OR: 0.90, 95% CI: 0.86, 0.93) while associations at higher intakes were near null. Mendelian randomization did not support a causal association between coffee intake and metabolic syndrome. Both self-reported and genetically predicted high coffee consumption (4 cups per day or more) were associated with central obesity. The inverse association between coffee consumption and metabolic syndrome was more profound among drinkers of ground coffee than those of instant coffee. Results were similar when stratified by the use of milk and sugar, yet the use of artificial sweetener with coffee was positively associated with metabolic syndrome and all component conditions.

Conclusions

Coffee consumption likely increase the risk of central obesity but unlikely impact risk of metabolic syndrome. The possible health effect of using artificial sweetener with coffee warrant investigations in future studies.
Elevated pre-treatment Neutrophil-to-lymphocyte and neutrophil-to-lymphocyte-platelet ratios are associated with a high risk of in-hospital death among patients with prostate cancer in Nigeria
Authors: Okoye Jude Ogechukwu , Ogbonnaya Vivian Ifunanya , Chiemeka Michael Emeka , Ogenyi Samuel Ifedioranma
Published: August 2023

Introduction

In the last decade, there is an increasing mortality rate among patients diagnosed with prostate cancer (PCa) in West Africa. To identify the causes of the high mortality rate, this study analyzed the occurrence of high-grade tumours and the presence of BRCA2 mutation. It also assessed the systemic inflammatory indices as prognostic tools in low-resource settings.

Methods

This study included 72 cases of PCa diagnosed from Jan. 2017 to Dec. 2020. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelets-neutrophils-to-lymphocytes ratio (PNLR), and neutrophils-to-lymphocytes platelets ratio (NLPR) were assessed and analyzed accordingly. Significance was set at p< 0.05.

Results

The prevalence of Gleason grades (G) 1 to 5 was 9.3%, 16.3%, 16.3%, 25.6, and 32.6%, respectively. There was a high frequency of BRCA2 mutation (58.3%) and the frequency was higher among patients with G4/5 tumours (59.5%) than in patients with G1-G3 tumours (46.7%) at p= 0.347. A high frequency of G4/5 tumours was observed among patients within the age group of 50-59 years (n= 7/8; 87.5%) and patients with castration-resistant PCa (n= 12/17; 70.6%). The pre-treatment PLR and calcium concentration were higher among patients with G4/5 tumours compared to patients with G1-G3 tumours (p= 0.046 and < 0.001, respectively.) There were direct relationships between BRCA2 expression and age (p= 0.019), tumour grade and calcium (p= 0.000), BRCA2 and calcium expression (p= 0.027), unemployment and G4/5 (p< 0.001), and education status and G4/5 (p= 0.020). The pretreatment NLR and NLPR were 2.0 and 4.7 times higher in in-hospital deaths than in stable discharges at p= 0.005 and 0.001, respectively.

Conclusion

This study revealed high frequencies of BRCA2 mutation and high-grade PCa in Southern Nigeria. It also suggests that pre-treatment PLR could be used to identify patients with G4/5 while pretreatment NLR and NLPR could be used to predict treatment outcomes.
Reproduction Number EXCEL Model of COVID-19 for predictive calculation of nearby trend up to the end of infection
Authors: Matsuda Shinzaburo , Toki Hiroshi
Published: August 2023

Reproduction Number (RN-)EXCEL Model has been developed on an EXCEL sheet to provide important characteristics of COVID-19 infectious disease for practical use. The model is developed based only on observed data to predict future infection toward herd immunity threshold and until the end stage of the infection. Basic equations are simple and constructed in analogy with neutron multiplication reactions in nuclear reactor. To know the next day infection, we calculate an exponential increase in one day step with a rate obtained from nearby PCR positive infectious numbers, which are daily input in the EXCEL sheet. In a closed community, main players are non-immune holders and immune holders, where total number of immune holders derived from infection and vaccination plays an essential role. In traditional SIR model, infection behavior is characterized by the reproduction rate in differential equation where social actions such as governmental regulations or vaccinations are included as constant breaking term for infection spread. However, in actual situation these terms are time dependent and is difficult to solve by a set of differential equations. In contrast, RN-EXCEL model deals with infection by defining successive reproduction number for each time interval as inchworm that represents a clear physical picture of the virus infectivity. Using this model, a lot of predictions were made for semi-closed communities domestically and world-wide, timely for practical use.
Increased Risk of Ischemic Stroke in Amyotrophic Lateral Sclerosis: A Nationwide Cohort Study in South Korea
Authors: Kwon Soonwook , Kim Bongseong , Han Kyung-Do , Jung Wonyoung , Cho Eun Bin , Shin Dong Wook , Min Ju-Hong
Published: August 2023

Background

We investigated the risk of ischemic stroke in ALS and analyzed the effect of ALS-related physical disability using the Korean National Health Insurance Service database.

Methods

A total of 2,252 ALS patients diagnosed between January 1, 2012, and December 31, 2015, and 1:10 age- and sex-matched control populations were included. After selection of cases that participated in the national health check-up programs, 659 ALS patients and 10,927 non-ALS participants were remained. Newly developing ischemic stroke as primary outcome was also defined by the ICD code and the incidence probability was assessed using by the Kaplan– Meier method during the follow-up duration. A Cox hazard regression model was used to examine the hazard ratios (HRs) for ischemic stroke in ALS after adjusting for potential confounders.

Results

ALS patients were younger than the control group (60.3 ± 10.2 years vs. 61.4 ± 10.5 years, p = 0.008), and the proportion of male patients was similar between the two groups (61.0% vs. 62.5%, p = 0.447). ALS patients were more likely to have a lower body mass index (23.1 ± 2.92 vs. 24.0 ± 3.00, p < 0.001) and be non-drinkers (64.2% vs. 57.4%, p = 0.002) than the controls. In ALS patients, the incidence of ischemic stroke was 7.8 per 1,000 person-years, and the adjusted HR of ischemic stroke was 3.67 (95% confidence interval 2.02−6.67) compared with the control group. The risk of ischemic stroke did not differ by the presence of disability in ALS patients.

Conclusions

Our findings suggest that ALS patients face increased risk of ischemic stroke compared with controls, but the risk did not differ by the presence of disability in ALS.
D-serine- andp-fluorophenylalanine-resistant mutants ofPhyscomitrium patensare defective in amino acid uptake
Authors: Albone Stephen , Cove David J , Ashton Neil W
Published: August 2023

Two amino acid analogue-resistant lines ofPhyscomitrium(formerlyPhyscomitrella)patens, DSR8andPFR4, are resistant to a range of D-amino acids and an inhibitory concentration of L-lysine. Both are defective in the uptake of [35S]-L-methionine. Uptake by the wild-type line is pH-dependent (decreasing with raised external proton concentrations) and is depressed by dinitrophenol and by ammonium ions. We discuss the possible involvement of an active proton-general amino acid antiport pump in the plasma membrane.
Phylogenetic and functional analyses ofN6-methyladenosine RNA methylation factors in the wheat scab fungusFusarium graminearum
Authors: Kim Hyeonjae , Hu Jianzhong , Kang Hunseung , Kim Wonyong
Published: August 2023

In eukaryotes,N6-methyladenosine (m6A) RNA modification plays crucial roles in governing the fate of RNA molecules and has been linked to various developmental processes. However, the phyletic distribution and functions of genetic factors responsible for m6A modification remain largely unexplored in fungi. To get insights into evolution of m6A machineries, we reconstructed global phylogenies of potential m6A writers, readers, and erasers in fungi. Substantial copy number variations were observed, ranging from up to five m6A writers in early-diverging fungi to a single copy in the subphylum Pezizomycotina, which primarily comprises filamentous fungi. To characterize m6A factors in a phytopathogenic fungusFusarium graminearum, we generated knockout mutants lacking potential m6A factors including the sole m6A writerMTA1. However, the resulting knockouts did not exhibit any noticeable phenotypic changes during vegetative and sexual growth stages. As obtaining a homozygous knockout lackingMTA1was likely hindered by its essential role, we generatedMTA1-overexpressing strains (MTA1-OE). TheMTA1-OE5 strain showed delayed conidial germination and reduced hyphal branching, suggesting its involvement during vegetative growth. Consistent with these findings, the expression levels ofMTA1and a potential m6A readerYTH1were dramatically induced in germinating conidia, followed by the expression of potential m6A erasers at later vegetative stages. Several genes including transcription factors, transporters and various enzymes were found to be significantly up- and down-regulated in theMTA1-OE5 strain. Overall, our study highlights the functional importance of the m6A methylation during conidial germination inF. graminearumand provides a foundation for future investigations into m6A modification sites in filamentous fungi.

Importance

N6-methyladenosine (m6A) RNA methylation is a reversible posttranscriptional modification that regulates RNA function and plays a crucial role in diverse developmental processes. This study addresses the knowledge gap regarding phyletic distribution and functions of m6A factors in fungi. The identification of copy number variations among fungal groups enriches our knowledge regarding the evolution of m6A machinery in fungi. Functional characterization of m6A factors in a phytopathogenic filamentous fungusFusarium graminearumprovides insights into the essential role of the m6A writerMTA1in conidial germination and hyphal branching. The observed effects of overexpressingMTA1on fungal growth and gene expression patterns of m6A factors throughout the life cycle ofF. graminearumfurther underscore the importance of m6A modification in conidial germination. Overall, this study significantly advances our understanding of m6A modification in fungi, paving the way for future research into its roles in filamentous growth and potential applications in disease control.
The Electron Transport Chain ofShewanella oneidensisMR-1 can Operate Bidirectionally to Enable Microbial Electrosynthesis
Authors: Ford Kathryne C. , TerAvest Michaela A.
Published: August 2023

Extracellular electron transfer (EET) is a process by which bacterial cells can exchange electrons with a redox active material located outside of the cell. InShewanella oneidensis, this process is natively used to facilitate respiration using extracellular electron acceptors such as Fe(III) or an anode. Previously, it was demonstrated that this process can be used to drive microbial electrosynthesis of 2,3-butanediol (2,3-BDO) inS. oneidensisexogenously expressing butanediol dehydrogenase (Bdh). Electrons taken into the cell from a cathode are used to generate NADH, which in turn is used to reduce acetoin to 2,3-BDO via Bdh. However, generating NADH via electron uptake from a cathode is energetically unfavorable, so NADH dehydrogenases couple the reaction to proton motive force. We therefore need to maintain the proton gradient across the membrane to sustain NADH production. This work explores accomplishing this task by bidirectional electron transfer, where electrons provided by the cathode go to both NADH formation and O2reduction by oxidases. We show that oxidases use trace dissolved oxygen in a microaerobic bioelectrical chemical systems (BES), and the translocation of protons across the membrane during O2reduction supports 2,3-BDO generation. Interestingly, this process is inhibited by high levels of dissolved oxygen in this system. In an aerated BES, O2molecules react with the strong reductant (cathode) to form reactive oxygen species, resulting in cell death.

Importance

Microbial electrosynthesis is increasingly employed for the generation of specialty chemicals such as biofuels, bioplastics, and cancer therapeutics. For these systems to be viable for industrial scale-up, it is important to understand the energetic requirements of the bacteria to mitigate unnecessary costs. This work demonstrates sustained production of an industrially relevant chemical driven by a cathode. Additionally, it optimizes a previously published system by removing any requirement for phototrophic energy, thereby removing the additional cost of providing a light source. We also demonstrate the severe impact of oxygen intrusion into bioelectrochemical systems, offering insight to future researchers aiming to work in an anaerobic environment. These studies provide insight into both the thermodynamics of electrosynthesis and the importance of bioelectrochemical systems design.
Microbial community organization during anaerobic pulp and paper mill wastewater treatment
Authors: Meyer Torsten , Yang Minqing Ivy , Nesbø Camilla , Master Emma , Edwards Elizabeth A.
Published: August 2023

Amplicon sequencing data and operating data from anaerobic wastewater treatment plants from three Canadian pulp and paper mills were explored using correlation and network modularization approaches to study the microbial community organization and identify relationships between organisms and operating conditions.

Each of the digesters contain two or three modules consisting of organisms that cover all trophic stages of anaerobic digestion. These modules are functioning independently from each other, and their relative abundance changes in response to varying operating conditions.

The time delay between a change in digester operation and the change in the abundance of microorganisms was investigated using time-lagged operating parameters. This time delay ranged between two to four days and is likely influenced by the growth rates of the anaerobic microorganisms and the digester hydraulic retention time.

Digester upsets due to plant shutdown periods and organic overload caused a drastic increase in the population of acetoclastic methanogens, acidogenic fermenters, and syntrophic acid degraders. As a response to impaired process conditions, the sameMethanothrixamplicon sequence variant (ASV) dominated methanogenesis in the digesters of all three mills. The common characteristics of the organisms represented by this ASV should be further investigated for their role in alleviating the impact of digester upset conditions.

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Unraveling the Half and Full Site Sequence Specificity of theSaccharomyces cerevisiaePdr1p and Pdr3p Transcription Factors
Authors: Buechel Evan R. , Pinkett Heather W.
Published: August 2023

The transcription factors Pdr1p and Pdr3p regulate pleotropic drug resistance (PDR) inSaccharomyces cerevisiae, via the PDR responsive elements (PDREs) to modulate gene expression. However, the exact mechanisms underlying the differences in their regulons remain unclear. Employing genomic occupancy profiling (CUT&RUN), binding assays, and transcription studies, we characterized the differences in sequence specificity between transcription factors. Findings reveal distinct preferences for core PDRE sequences and the flanking sequences for both proteins. While flanking sequences moderately alter DNA binding affinity, they significantly impact Pdr1/3p transcriptional activity. Notably, both proteins demonstrated the ability to bind half sites, showing potential enhancement of transcription from adjacent PDREs. This insight sheds light on ways Pdr1/3 can differentially regulate PDR.