bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Genomes Reveal Evolutionary Relationships and Mechanisms Underlying Gene-Tree Discordance inNeodiprionSawflies
Authors: Herrig Danielle K. , Vertacnik Kim L. , Ridenbaugh Ryan D. , Everson Kathryn M. , Sim Sheina B. , Geib Scott M. , Weisrock David W. , Linnen Catherine R.
Published: January 2023

Abstract

Rapidly evolving taxa are excellent models for understanding the mechanisms that give rise to biodiversity. However, developing an accurate historical framework for comparative analysis of such lineages remains a challenge due to ubiquitous incomplete lineage sorting and introgression. Here, we use a whole-genome alignment, multiple locus-sampling strategies, and locus-based and SNP-based species-tree methods to infer a species tree for eastern North AmericanNeodiprionspecies, a clade of pine-feeding sawflies (Order: Hymenopteran; Family: Diprionidae). We recovered a well-supported species tree that—except for three uncertain relationships—is robust to different strategies for analyzing whole-genome data. Despite this consistency, underlying gene-tree discordance is high. To understand this discordance, we use multiple regression to model topological discordance as a function of several genomic features. We find that gene-tree discordance tends to be higher in regions of the genome that may be more prone to gene-tree estimation error, as indicated by a lower density of parsimony-informative sites, a higher density of genes, a higher average pairwise genetic distance, and gene trees with lower average bootstrap support. Also, contrary to the expectation that discordance via incomplete lineage sorting is reduced in low-recombination regions of the genome, we find anegativecorrelation between recombination rate and topological discordance. We offer potential explanations for this pattern and hypothesize that it may be unique to lineages that have diverged with gene flow. Our analysis also reveals an unexpected discordance hotspot on Chromosome 1, which contains several genes potentially involved in mitochondrial-nuclear interactions and produces a gene-tree that resembles a highly discordant mitochondrial tree. Based on these observations, we hypothesize that our genome-wide scan for topological discordance has identified a nuclear locus involved in a mito-nuclear incompatibility. Together, these results demonstrate how phylogenomic analysis coupled with high-quality, annotated genomes can generate novel hypotheses about the mechanisms that drive divergence and produce variable genealogical histories across genomes.
A parametric model for estimating the timing and intensity of animal migration
Authors: Thompson Peter R. , Harrington Peter D. , Mallory Conor D. , Lele Subhash R. , Bayne Erin M. , Derocher Andrew E. , Edwards Mark A. , Campbell Mitch , Lewis Mark A.
Published: January 2023

Animals of many different species, trophic levels, and life history strategies migrate, and the improvement of animal tracking technology allows ecologists to collect increasing amounts of detailed data on these movements. Understanding when animals migrate is important for managing their populations, but is still difficult despite modelling advancements. We designed a model that parametrically estimates the timing of migration from animal tracking data. Our model identifies the beginning and end of migratory movements as signaled by changes in step length and turning angle distributions. To this end, we can also use the model to estimate how an animal’s movement changes when it begins migrating. We tested our model on three datasets: migratory ferruginous hawks (Buteo regalis) in the Great Plains and barren-ground caribou (Rangifer tarandus groenlandicus) in northern Canada, and non-migratory brown bears (Ursus arctos) from the Canadian Arctic. We estimated the beginning and end of migration in caribou and hawks to the nearest day, while confirming a lack of migratory behaviour in the brown bear population. The flexibility of our modelling framework allowed us to assess intricacies associated with each dataset: long-term stopover behaviour in ferruginous hawks anda prioriknowledge of caribou calving areas and behaviour. In addition to estimating when caribou and ferruginous hawks migrated, our model also identified differences in how the two populations migrated; ferruginous hawks achieved efficient migrations by increasing their movement rates while caribou migration was achieved through significant increases in directional persistence. Our approach is broadly applicable to many animal movement studies. We anticipate that rigorous assessment of migration metrics will aid understanding of both how and why animals move.
Ongoing amphibian trade into the United States threatens salamander biodiversity
Authors: Connelly Patrick J. , Ross Noam , Stringham Oliver C. , Eskew Evan A.
Published: January 2023

The fungal pathogenBatrachochytrium salamandrivorans(Bsal) is a major potential threat to salamander biodiversity in North America, where it is not yet known to occur. In the United States, a 2016 policy restricted the trade in 20 salamander genera in attempts to preventBsalintroduction. However, little comprehensive data is available to evaluate the impact of this policy action. Here, we collated a dataset of United States amphibian imports from 1999 to 2021 and show that reported legal trade in the targeted taxa was effectively reduced by the ban. Unfortunately, amphibian trade into the United States continues to riskBsalintroduction given that other species and genera now known to carryBsalare still traded in large quantities (millions of live individuals annually). Additional policy responses focused onBsalcarrier taxa, especially frogs in the genusRana, could help mitigate the impact ofBsalon North American salamanders.
Somatic mutation but not aneuploidy differentiates lung cancer in never-smokers and smokers
Authors: Moorthi Sitapriya , Paguirigan Amy , Ko Minjeong , Pettinger Mary , Hoge Anna C. H. , Nag Anwesha , Patel Neil A. , Wu Feinan , Sather Cassie , Fitzgibbon Matthew P. , Thorner Aaron R. , Anderson Garnet L. , Ha Gavin , Berger Alice H.
Published: January 2023

Lung cancer in never-smokers disproportionately affects older women. To understand the mutational landscape of this cohort, we performed detailed genome characterization of 73 lung adenocarcinomas from participants of the Women’s Health Initiative (WHI). We find enrichment ofEGFRmutations in never-/light-smokers andKRASmutations in heavy smokers as expected, but we also show that the specific variants of these genes differ by smoking status, with important therapeutic implications. Mutational signature analysis revealed signatures of clock, APOBEC, and DNA repair deficiency in never-/light-smokers; however, the mutational load of these signatures did not differ significantly from those found in smokers. Last, tumors from both smokers and never-/light-smokers shared copy number subtypes, with no significant differences in aneuploidy. Thus, the genomic landscape of lung cancer in never-/light-smokers and smokers is predominantly differentiated by somatic mutations and not copy number alterations.
Joint effects of social interactions and environmental challenges on physiology, internal microbiome, and reproductive performance in tree swallows (Tachycineta bicolor)
Authors: Taff Conor C. , McNew Sabrina M. , Zimmer Cedric , Uehling Jennifer J. , Houtz Jennifer L. , Ryan Thomas A. , van Oordt David Chang , Injaian Allison S. , Vitousek Maren N.
Published: January 2023

The social environment that individuals experience appears to be a particularly salient mediator of stress resilience, as the nature and valence of social interactions are often related to subsequent health, physiology, microbiota, and overall stress resilience. Relatively few studies have simultaneously manipulated the social environment and ecological challenges under natural conditions. Here, we report the results of experiments in wild tree swallows (Tachycineta bicolor) in which we manipulated both ecological challenges (predator encounters and flight efficiency reduction) and social interactions (by experimental dulling of a social signal). In two experiments conducted in separate years, we reversed the order of these treatments so that females experienced either an altered social environment followed by a challenge or vice-versa. Before, during, and after treatments were applied, we tracked breeding success, morphology and physiology (mass, corticosterone, and glucose), social interactions via an RFID sensor network, cloacal microbiome diversity, and fledging success. Overall, we found that predator exposure during the nestling period reduced the likelihood of fledging and that signal manipulation sometimes altered social interactions, but little evidence that the two categories of treatment interacted with each other. We discuss the implications of our results for understanding what types of challenges and what conditions are most likely to result in interactions between the social environment and ecological challenges.
Leafhopper transmits soybean stay-green associated virus to legume plants
Authors: Yin Jinlong , Hu Zhuangzhuang , Xu Shuqi , Hong Xin , Qiu Yanglin , Cheng Xinge , Wang Liqun , Shen Weiliang , Zhi Haijian , Li Kai , Xu Kai
Published: January 2023

A novel geminivirus, soybean stay-green associated virus (SoSGV), was previously shown to cause soybean delayed senescence and is associated with the incidences of soybean stay-green syndrome. The transmission methods of SoSGV were not yet understood. We captured insects belonging to 24 distinct species in a soybean field with the SoSGV outbreak and detected the presence of SoSGV only in leafhoppers and bean bugs (Riptortus pedestris). Caged feeding experiments using captured leafhoppers and bean bugs from soybean fields showed that leafhoppers, but not bean bugs, are vectors transmitting SoSGV. The common brown leafhopper (Orosius orientalis) is identified as the dominant leafhopper species and can establish colonies feeding on soybean plants in experimental conditions. An investigation of SoSGV defective DNA revealed that soybean genomic DNA could be inserted into the SoSGV genome, while sequences from wild soybean, red bean, and cowpea were also identified. We further showed that the common brown leafhopper could transmit SoSGV to wild soybean and red bean plants, emphasizing the vector role of the leafhopper in the transmission of SoSGV in the field.
When Geometric Deep Learning Meets Pretrained Protein Language Models
Authors: Wu Fang , Tao Yu , Radev Dragomir , Xu Jinbo
Published: January 2023

Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the limited quantity of structural data. Meanwhile, protein language models trained on substantial 1D sequences have shown burgeoning capabilities with scale in a broad range of applications. Nevertheless, no preceding studies consider combining these different protein modalities to promote the representation power of geometric neural networks. To address this gap, we make the foremost step to integrate the knowledge learned by well-trained protein language models into several state-of-the-art geometric networks. Experiments are evaluated on a variety of protein representation learning benchmarks, including protein-protein interface prediction, model quality assessment, protein-protein rigid-body docking, and binding affinity prediction, leading to an overall improvement of 20% over baselines and the new state-of-the-art performance. Strong evidence indicates that the incorporation of protein language models’ knowledge enhances geometric networks’ capacity by a significant margin and can be generalized to complex tasks.
Evaluation Of Effect Of Bacteria On The Surface Of The Dental Implant
Authors: George S. Ajrish , Muralidharan N.P. , S Sahana , N Thiyaneswaran , R Subhashree
Published: January 2023

Background

Dental Implantology is the most preferred treatment among patients who are opting for the replacement of their missing teeth. It is said that the success of the dental depends on the effectiveness of the dental implant bonding to the maxilla/mandible. This effectiveness depends on many factors. The microbial flora surrounding the dental implant also affects the integrity of the dental implant.

Aim

The study aims to analyze any effect bacteria on the surface of the implant.

Materials and methods

In the present study, 10 sterile dental implants were taken. Plaque samples were collected from patients with poor oral hygiene, who underwent dental implants and were under review for more than one month to six months. It was incubated with broth at 37 degrees Celcius. The surface changes in the dental implant were then observed in a scanning electron microscope.

Results

The SEM results show a significant difference in the surface texture of the implant. There were pits, small craters, and cracks on the surface. The sharpness of the screw thread had also been noticeably blunt.

Conclusion

Thus the study concludes that bacteria have a significant effect on the surface of the dental implant.
Zika virus infection induces IL-1β-mediated inflammatory responses by macrophages in the brain of an adult mouse model
Authors: Jeong Gi Uk , Lee Sumin , Kim Do Yeon , Lyu Jaemyun , Yun Gun Young , Ko Junsu , Kwon Young-Chan
Published: January 2023

During the 2015/16 Zika virus (ZIKV) epidemic, ZIKV associated neurological diseases were reported in adults, including microcephaly, Guillain-Barre syndrome, myelitis, meningoencephalitis, and fatal encephalitis. However, the mechanisms underlying the neuropathogenesis of ZIKV infection are not yet fully understood. In this study, we used an adult ZIKV-infection mouse model (Ifnar1−/−) to investigate the mechanisms underlying neuroinflammation and neuropathogenesis. ZIKV infection induced the expression of proinflammatory cytokines, including IL-1β, IL-6, IFN-γ, and TNF-α, in the brains ofIfnar1−/−mice. RNA-seq analysis of the infected mouse brain also revealed that genes involved in innate immune responses and cytokine-mediated signaling pathways were significantly upregulated at 6 days post infection. Furthermore, ZIKV infection induced macrophage infiltration and activation, and augmented IL-1β expression, whereas microgliosis was not observed in the brain. Using human monocyte THP-1 cells, we confirmed that ZIKV infection promotes inflammatory cell death and increases IL-1β secretion. In addition, the expression of complement component C3, which is associated with neurodegenerative diseases and known to be upregulated by proinflammatory cytokines, was induced by ZIKV infection through the IL-1β-mediated pathway. An increase in C5a produced by complement activation in the brains of ZIKV-infected mice was also confirmed. Taken together, our results suggest that ZIKV infection of the brain in this animal model augments IL-1β expression in infiltrating macrophages and elicits IL-1β-mediated inflammation, which can lead to the destructive consequences of neuroinflammation.

Importance

Zika virus (ZIKV) associated neurological impairments are an important global health problem. Our results suggest that ZIKV infection of the mouse brain can induce IL-1β-mediated inflammation and complement activation, contributing to the development of neurological disorders. Thus, our findings reveal a mechanism by which ZIKV induces neuroinflammation in the mouse brain. Although we used adult type I IFN receptor IFNAR knockout (Ifnar1−/−) mice owing to the limited mouse model of ZIKV pathogenesis, our conclusion could contribute to understanding ZIKV associated neurological diseases to develop treatment strategies based on these findings for the patients with ZIKV infection.
Genetic Networks of Alzheimer’s Disease, Aging and Longevity in Humans
Authors: Balmorez Timothy , Sakazaki Amy , Murakami Shin
Published: January 2023

Human genomic analysis and genome-wide association studies (GWAS) have identified genes that are risk factors for early and late-onset Alzheimer’s disease (AD genes). Although the genetics of aging and longevity has been extensively studied, previous studies have focused on a specific set of genes that have been shown to contribute to or to be a risk factor for AD. Thus, the connections among the genes involved in AD, aging, and longevity are not well understood. Here, we identified the genetic interaction networks (referred to as pathways) of aging and longevity within the context of AD, using a gene set enrichment analysis by Reactome that cross-references more than 100 bioinformatic databases to allow interpretation of the biological functions of gene sets through a wide variety of gene networks. We validated the pathways with a threshold of p-value < 1.00E-05, using the databases to extract lists of 356 AD genes, 307 aging-related (AR) genes, and 357 longevity genes. There was a broad range of biological pathways involved in AR and Longevity genes shared with AD genes. AR genes identified 261 pathways within the threshold of p < 1.00E-05, of which 26 pathways (10% of AR gene pathways) were further identified by overlapping genes among AD and AR genes. The overlapped pathways included Gene Expression (p = 4.05E-11) including ApoE, SOD2, TP53 and TGFB1 (p = 2.84E-10); Protein Metabolism and SUMOylation including E3 ligases and target proteins (p = 1.08E-07), ERBB4 signal transduction (p = 2.69E-06), Immune System including IL-3 and IL-13 (p = 3.83E-06), Programmed Cell Death (p = 4.36E-06) and platelet degranulation (p = 8.16E-06) among others. Longevity genes identified 49 pathways within the threshold, of which 12 pathways (24% of Longevity gene pathways) were further identified by overlapping genes among AD and Longevity genes. They include the immune system including IL-3 and IL-13 (p = 7.64E-08), plasma lipoprotein assembly, remodeling and clearance (p < 4.02E-06), metabolism of fat-soluble vitamins (p = 1.96E-05). Thus, this study provides shared genetic hallmarks of aging, longevity, and AD backed up by statistical significance. We discuss significant genes involved in these pathways, including TP53, FOXO, Sumoylation, IL4, IL6, APOE, and CEPT, and suggest that mapping the gene network pathways provide a useful basis for further medical research, education, and community outreach.
“Novel Clinical Manifestations of Human Monkeypox Virus Infection and Current Therapeutic and Preventive Strategies: A Systematic Review “
Authors: Chenchula Santenna , Ghanta Mohan Krishna , Chavan Madhavrao , Amerneni Krishna Chaitanya , Padmavathi R , Gupta Rupesh
Published: January 2023

The escalating global monkeypox cases since early May 2022, acquired by the monkeypox virus (MPXV), a double-stranded DNA virus has been declared a public health emergency of international concern by the World Health Organization (WHO). Globally as of December 2022, the MPXV was transmitted to more than 100 countries with around 82,550 cases, among which 81577 cases from the 103 countries that are non-endemic to the MPXV with more than 50 deaths. The ripple effect of the Monkeypox outbreak in nonendemic countries globally could potentially bring significant challenges to worldwide health systems if the spread of the virus is not effectively controlled. In this urgent situation, only three antiviral drugs are in use against monkeypox infections and are not specific against monkeypox, hence the scientific communities across the world are in search to explore vaccines or therapeutic antiviral drugs selectively against the monkeypox virus. Here, in the present review, we discuss the clinical characteristics and treatment outcomes of the ongoing MPX outbreak of 2022 in nonendemic countries globally, from the published and grey literature in PubMed, Scopus and Google scholar. A total of 17 studies with 17,811 of MPX cases were found and included in the final qualitative analysis of the current systematic review.
The interplay between pre-season population susceptibility and the effectiveness of the rolled out vaccination control the timing and size of an emerging seasonal influenza wave in England
Authors: van Leeuwen E. , Panovska-Griffiths J. , Elgohari S. , Charlett A. , Watson C.
Published: January 2023

1.

Relaxing social distancing measures and reduced level of influenza over the last two seasons may lead to a winter 2022 influenza wave in England. We used an established model for influenza transmission and vaccination to evaluate the rolled out influenza immunisation programme over October to December 2022. Specifically, we explored how the interplay between pre-season population susceptibility and influenza vaccine efficacy control the timing and the size of a possible winter influenza wave. Our findings suggest that susceptibility affects the timing and the height of a potential influenza wave, with higher susceptibility leading to an earlier and larger influenza wave while vaccine efficacy controls the size of the peak of the influenza wave. With pre-season susceptibility higher than pre-COVID-19 levels, under the planned vaccine programme an early influenza epidemic wave is possible, its size dependent on vaccine effectiveness against the circulating strain. If pre-season susceptibility is low and similar to pre-COVID levels, the planned influenza vaccine programme with an effective vaccine could largely suppress a winter 2022 influenza outbreak in England.
Patient perspectives and hospital pay-for-performance: A qualitative study from Lebanon
Authors: Khalife Jade , Ekman Björn , Ammar Walid , El-Jardali Fadi , Halabi Abeer Al , Barakat Elise , Emmelin Maria
Published: January 2023

Background

Patient perspectives have received increasing importance within health systems over the past four decades. Measures of patient experience and satisfaction are commonly used. However, these do not capture all the information available through patient engagement. An improved understanding of the various types of patient perspectives and the distinctions between them is needed. The lack of such knowledge limits the usefulness of including patient perspectives as components within pay-for-performance initiatives. This study was aimed to identify and explore patient perspectives on hospital care in Lebanon, and to describe how they relate to the national pay-for-performance initiative.

Methods

We conducted a qualitative study using focus group discussions with persons recently discharged after hospitalization under the coverage of the Lebanese Ministry of Public Health. This study was implemented in 2017 and involved 42 participants across eight focus groups. Qualitative content analysis was used to analyze the information provided by participants.

Results

Five overall themes supported by 17 categories were identified, capturing the meaning of the informants’ perspectives: health is everything; being turned into second class citizens; money and ‘wasta’ (personal connections) make all the difference; wanting to be treated with dignity and respect; and tolerating letdown, for the sake of right treatment. The most frequently prioritized statement in a ranking exercise regarding patient satisfaction was regular contact with one’s doctor.

Conclusions

Patient perspectives include more than what is traditionally incorporated in measures of patient satisfaction and experience. Patient valuing of health and their perceptions on each of the health system, and access and quality of care should also be taken into account. Hospital pay-for-performance initiatives can be made more responsive through a broader consideration of these perspectives. More broadly, health systems would benefit from wider engagement of patients. We propose a framework relating patient perspectives to value-based healthcare and health system performance.
Joint estimation and imputation of variant functional effects using high throughput assay data
Authors: Yu Tian , Fife James D. , Adzhubey Ivan , Sherwood Richard , Cassa Christopher A.
Published: January 2023

Deep mutational scanning assays enable the functional assessment of variants in high throughput. Phenotypic measurements from these assays are broadly concordant with clinical outcomes but are prone to noise at the individual variant level. We develop a framework to exploit related measurements within and across experimental assays to jointly estimate variant impact. Drawing from a large corpus of deep mutational scanning data, we collectively estimate the mean functional effect per AA residue position within each gene, normalize observed functional effects by substitution type, and make estimates for individual allelic variants with a pipeline called FUSE (FunctionalSubstitutionEstimation). FUSE improves the correlation of functional screening datasets covering the same variants, better separates estimated functional impacts for known pathogenic and benign variants (ClinVarBRCA1, p=2.24×10−51), and increases the number of variants for which predictions can be made (2,741 to 10,347) by inferring additional variant effects for substitutions not experimentally screened. For UK Biobank patients who carry a rare variant inTP53, FUSE significantly improves the separation of patients who develop cancer syndromes from those without cancer (p=1.77×10−6). These approaches promise to improve estimates of variant impact and broaden the utility of screening data generated from functional assays.

Graphical Abstract

Highlights

Uses functional assay data collectively to improve the estimation of allelic variant effects

Infers the impact of variants not experimentally screened, broadening the utility of assays

Improves the discrimination of clinically actionable variants within ClinVar

Significantly separates patients at risk for cancer syndromes in the UK Biobank
Multi-scale transcriptome unveils spatial organisation and temporal dynamics ofBacillus subtilisbiofilms
Authors: Dergham Yasmine , Coq Dominique Le , Nicolas Pierre , Deschamps Julien , Huillet Eugénie , Sanchez-Vizuete Pilar , Hamze Kassem , Briandet Romain
Published: January 2023

Bacillus subtilishas been extensively used to study the molecular mechanisms behind the development and dispersal of surface bacterial multicellular communities. Well-structured spatially organised communities (colony, pellicle, and submerged biofilm) share some similarities, but also display considerable differences at the structural, chemical and biological levels. To unveil the spatial transcriptional heterogeneity between the different communities, we analysed by RNA-seq nine spatio-physiological populations selected from planktonic and spatially organised communities. This led to a global landscape characterisation of gene expression profiles uncovering genes specifically expressed in each compartmental population. From this mesoscale analysis and using fluorescent transcriptional reporter fusions, 17 genes were selected and their patterns of expression reported at single cell scale with time-lapse confocal laser scanning microscopy (CLSM). Derived kymographs allowed to emphasise spectacular mosaic gene expression patterns within a biofilm. A special emphasis on oppositely regulated carbon metabolism genes (gapAandgapB) permitted to pinpoint the coexistence of spatially segregated bacteria under either glycolytic or gluconeogenic regime in a same biofilm population. Altogether, this study gives novel insights on the development and dispersal ofB. subtilissurface-associated communities.
A strongly improved assembly of the pearl millet reference genome using Oxford Nanopore long reads and optical mapping
Authors: Salson Marine , Orjuela Julie , Mariac Cédric , Zekraouï Leïla , Couderc Marie , Arribat Sandrine , Rodde Nathalie , Faye Adama , Kane Ndjido A. , Tranchant-Dubreuil Christine , Vigouroux Yves , Berthouly-Salazar Cécile
Published: January 2023

Pearl millet (Pennisetum glaucum(L.)) R. Br. syn.Cenchrus americanus(L.) Morrone) is an important crop in South Asia and sub-Saharan Africa which contributes to ensure food security. Its genome has an estimated size of 1.76 Gb and displays a high level of repetitiveness above 80%. A first assembly was previously obtained for the Tift 23D2B1-P1-P5 cultivar genotype using short-read sequencing technologies. This assembly is however incomplete and fragmented with around 200 Mb unplaced on chromosomes. We report here an improved quality assembly of the pearl millet Tift 23D2B1-P1-P5 cultivar genotype obtained with an approach combining Oxford Nanopore long reads and Bionano Genomics optical maps. This strategy allowed us to add around 200 Mb at the chromosome-level assembly. Moreover we strongly improved continuity in the order of the contigs and scaffolds wihtin the chromosomes, particularly in the centromeric regions. Notably, we added more than 100 Mb around the centromeric region on chromosome 7. This new assembly also displayed a higher gene completeness with a complete BUSO score of 98.4% using the Poales database. This more complete and higher quality assembly of the Tift 23D2B1-P1-P5 genotype now available to the community will help in the development of research on the role of structural variants, and more broadly in genomics studies and the breeding of pearl millet.
Myddosome clustering in IL-1 receptor signaling regulates the formation of an NF-kB activating signalosome
Authors: Cao Fakun , Deliz-Aguirre Rafael , Gerpott Fenja H. U. , Ziska Elke , Taylor Marcus J.
Published: January 2023

Signaling pathways can produce digital invariant outputs and analog outputs that scale with the amount of stimulation. In IL-1 receptor (IL-1R) signaling both types of outputs require the Myddosome, a multi-protein complex. The Myddosome is required for polyubiquitin chain formation and NF-kB signaling. However, the ways in which these signals are spatially and temporally regulated to drive switch-like and proportional outcomes is not understood. We find that during IL-1R signaling, Myddosomes dynamically re-organize into large, multi-Myddosome clusters at the cell membrane. Blockade of Myddosome clustering using nanoscale extracellular barriers reduces NF-kB activation. We find that Myddosomes function as a scaffold that assembles an NF-kB signalosome consisting of E3-ubiquitin ligases TRAF6 and LUBAC, K63/M1-linked polyubiquitin chains, phospho-IKK, and phospho-p65. This signalosome preferentially assembles at regions of high Myddosome density, which enhances the recruitment of TRAF6 and LUBAC. Extracellular barriers that restrict Myddosome clustering perturbed the recruitment of both ligases. We found that LUBAC was especially sensitive to clustering with a sevenfold lower recruitment to single Myddosomes than clustered Myddosomes. This data reveals that the clustering behavior of Myddosome provides the basis for digital and analog IL-1R signaling.
Thermodynamic limitations on brain oxygen metabolism: physiological implications
Authors: Buxton Richard B.
Published: January 2023

A recent hypothesis is that maintaining the brain tissue ratio of O2to CO2is critical for preserving the entropy increase available from oxidative metabolism of glucose, with a fall of that available entropy leading to a reduction of the phosphorylation potential and impairment of brain energy metabolism. The hypothesis suggests that physiological responses under different conditions can be understood as preserving tissue O2/CO2. To test this idea, a mathematical model of O2and CO2transport was used to calculate how well different physiological responses maintain tissue O2/CO2, showing good agreement with reported experimental measurements for increased neural activity, hypercapnia and hypoxia. The results highlight the importance of thinking about brain blood flow as a way to modulate tissue O2/CO2, rather than simply in terms of O2delivery to the capillary bed. The hypoxia modeling focused on humans at high altitude, including acclimatized lowlanders and adapted populations, with a primary finding that decreasing CO2by increasing ventilation rate is much more effective for preserving tissue O2/CO2than increasing blood hemoglobin content. The modeling provides a new framework and perspective for understanding how blood flow and other physiological factors support energy metabolism in the brain under a wide range of conditions.

Key points summary

Recent thermodynamic modeling suggests that preserving the O2/CO2ratio in brain tissue is critical for preserving the entropy change available from the oxidative metabolism of glucose and the phosphorylation potential underlying energy metabolism.

The hypothesis tested is that normal physiological responses (notably blood flow changes) often act to preserve this ratio under changing conditions.

Using a detailed model to calculate tissue O2/CO2we found good agreement with the predictions of the hypothesis and reported experimental results during hypoxia, hypercapnia and increased oxygen metabolic rate in response to increased neural activity.

For the hypoxia modeling we considered high altitude acclimatization and adaptation in humans, showing the critical role of reducing CO2in preserving tissue O2/CO2.

The tissue O2/CO2hypothesis provides a useful perspective for understanding the function of observed physiological responses under different conditions in terms of preserving brain energy metabolism, although the mechanisms underlying these functions are not well understood.
A major 6 Mb superlocus is involved in pyrethroid resistance in the common bed bugCimex lectularius
Authors: Haberkorn Chloé , David Jean-Philippe , Henri Hélène , Delpuech Jean-Marie , Lasseur Romain , Vavre Fabrice , Varaldi Julien
Published: January 2023

In the last few years, the bed bugCimex lectulariushas been an increasing problem world-wide, mainly due to the development of insecticide resistance to pyrethroids. The characterization of resistance alleles is a prerequisite to improve surveillance and resistance management. To identify genomic variants associated with pyrethroid resistance inCimex lectularius, we compared the genetic composition of two recent and resistant populations with that of two ancientsusceptible strains using a genome-wide pool-seq design. We identified a large 6 Mb “superlocus” showing particularly high genetic differentiation and association with the resistance phenotype. This superlocus contained several clustered resistance genes, and was also characterized by a high density of structural variants (inversions, duplications). The possibility that this superlocus constitutes a resistance “supergene” that evolved after the clustering of alleles adapted to insecticide and after reduction in recombination is discussed.
RabbitVar: ultra-fast and accurate somatic small-variant calling on multi-core architectures
Authors: Zhang Hao , Song Honglei , Yin Zekun , Chang Qixin , Wei Yanjie , Niu Beifang , Schmidt Bertil , Liu Weiguo
Published: January 2023

The continuous development of next-generation sequencing (NGS) technology has led to extensive and frequent use of genomic analysis in cancer research. The associated production of large-scale NGS datasets establishes the need for high-precision somatic variant calling methods that are highly optimized on commonly used hardware platforms. We present RabbitVar (https://github.com/LeiHaoa/RabbitVar), a scalable variant caller that can detect small somatic variants from paired tumor/normal NGS data on modern multi-core CPUs. Our approach combines candidate-finding and machine-learning-based filtering strategies with optimized data structures and multi-threading to achieve both high accuracy and efficiency. We have compared the performance of RabbitVar to leading state-of-the-art callers (Strelka2, Mutect2, NeuSomatic, VarDict, VarScan2) on real-world HCC1395 breast cancer datasets under different sequencing conditions and contamination rates. The evaluation results demonstrate that RabbitVar achieves highly competitive F1-scores when calling SNVs. Moreover, when calling the more challenging indel variants, it consistently achieves the highest F1-scores. RabbitVar is able to process a paired tumor and normal whole human genome sequencing datasets with 80x depth in less than 20 minutes on a 48-core workstation outperforming all other tested variant callers in terms of efficiency.
Plants sum and subtract stimuli over different timescales
Authors: Rivière Mathieu , Meroz Yasmine
Published: January 2023

Mounting evidence suggests that plants engage complex computational processes to quantify and integrate sensory information over time, enabling remarkable adaptive growth strategies. However, quantitative understanding of these computational processes is limited. We report experiments probing the dependence of gravitropic responses of wheat coleoptiles on previous stimuli. First, building on a mathematical model that identifies this dependence as a form of memory, or a filter, we use experimental observations to reveal the mathematical principles of how coleoptiles integrate multiple stimuli over time. Next, we perform two-stimulus experiments, informed by model predictions, to reveal fundamental computational processes. We quantitatively show that coleoptiles respond not only to sums but also to differences between stimuli over different timescales, constituting first evidence that plants can compare stimuli – crucial for search and regulation processes. These timescales also coincide with oscillations observed in gravitropic responses of wheat coleoptiles, suggesting shoots may combine memory and movement in order to enhance posture control and sensing capabilities.
Somatostatin-expressing neurons in the ventral tegmental area innervate specific forebrain regions and are involved in the stress response
Authors: Nagaeva Elina , Schäfer Annika , Linden Anni-Maija , Elsilä Lauri V. , Ryazantseva Maria , Umemori Juzoh , Egorova Ksenia , Korpi Esa R.
Published: January 2023

Expanding knowledge about the cellular composition of subcortical brain regions demonstrates large heterogeneity and differences from the cortical architecture. Recently, we described three subtypes of somatostatin-expressing (Sst) neurons in the mouse ventral tegmental area (VTA) and showed their local inhibitory action on the neighbouring dopaminergic neurons (Nagaeva et al., 2020). Here, we report that VTA Sst neurons especially from the anterolateral part also project far outside the VTA and innervate several forebrain regions that are mainly involved in the regulation of emotional behaviour. Deletion of these VTA Sst neurons affected several behaviours and drug responses, such as home cage activity, sensitization of locomotor activity to morphine, fear conditioning responses, and reactions to inescapable stress of forced swimming, often in a sex-dependent manner. Together, these data demonstrate that VTA Sst neurons have selective projection targets, which are distinct from the main targets of VTA dopamine neurons and involved in the regulation of a variety of behaviours mostly associated with the stress response. This, makes Sst neurons a meaningful addition to the remote VTA circuit and stress-related neuronal network.
Mechanistic insight into substrate specificity of plant glucosinolate transporters
Authors: Kanstrup Christa , Wulff Nikolai , Peña-Varas Carlos , Jørgensen Morten Egevang , Bang-Sørensen Rose , Crocoll Christoph , Jørgensen Flemming Steen , Ramírez David , Dreyer Ingo , Mirza Osman , Nour-Eldin Hussam H.
Published: January 2023

Plants depend on transport processes for correct allocation of specialized metabolites. This is important for optimal defense, avoidance of autotoxicity, connecting compartmented biosynthetic modules and more. Transport of a wide variety of specialized metabolites is mediated by transporters from the Nitrate and Peptide transporter Family (NPF), which belongs to the Major Facilitator Superfamily (MFS). However, the mechanism by which NPF members recognize and transport specialized metabolites remains unknown.

Here we mutate eight residues to reciprocally swap the substrate-preference of two closely related glucosinolate transporters (GTRs). Seven of these residues assemble in a ring-like structure in all conformations of the transporters. We labeled the ring-like structure a selectivity filter and based on docking studies, we propose that the interaction between the selectivity filter and the glucosinolate side chain determines whether a given glucosinolate is recognized as a substrate. Besides partly explaining the distinct substrate preference of GTR1 (NPF2.10) and GTR3 (NPF2.9), this study proposes fundamental principles of substrate recognition in the NPF and establishes the GTR subclade as a novel model system for studying structure function relationships in the NPF.
RBM43 links adipose inflammation and energy expenditure through translational regulation of PGC1α
Authors: Dumesic Phillip A. , Wilensky Sarah E. , Bose Symanthika , Van Vranken Jonathan G. , Gygi Steven P. , Spiegelman Bruce M.
Published: January 2023

Adipose thermogenesis involves specialized mitochondrial function that counteracts metabolic disease through dissipation of chemical energy as heat. However, inflammation present in obese adipose tissue can impair oxidative metabolism. Here, we show that PGC1α, a key governor of mitochondrial biogenesis and thermogenesis, is negatively regulated at the level of mRNA translation by the little-known RNA-binding protein RBM43.Rbm43is expressed selectively in white adipose depots that have low thermogenic potential, and is induced by inflammatory cytokines. RBM43 suppresses mitochondrial and thermogenic gene expression in a PGC1α-dependent manner and its loss protects cells from cytokine-induced mitochondrial impairment. In mice, adipocyte-selectiveRbm43disruption increases PGC1α translation, resulting in mitochondrial biogenesis and adipose thermogenesis. These changes are accompanied by improvements in glucose homeostasis during diet-induced obesity that are independent of body weight. The action of RBM43 suggests a translational mechanism by which inflammatory signals associated with metabolic disease dampen mitochondrial function and thermogenesis.
Relationships between competition sprint cycling power and endurance power are high across ALL durations and energetic pathways
Authors: Ferguson Hamish , Harnish Chris , Klich Sebastian , Michalik Kamil , Dunst Anna Katharina , Zhou Tony , Chase J. Geoffrey
Published: January 2023

This study investigates associations between power at several durations to show inter- relationships of power across a range of durations in sprint track cyclists. The currently-accepted hypothesis peak power holds a near perfect relationship with sprint performance, and thus a near 1:1 slope with power at sprint durations up to 30-s, is tested. The equally well-accepted and complementary hypothesis there is no strong association with power over longer durations is also tested. 56 data sets from 27 cyclists (21 male, 6 female) provided maximal power for durations from 1-s to 20-min. Peak power values are compared to assess strength of correlation (R2), and any relationship (slope) across every level. R2between 15-s – 30-s power and durations from 1-s to 20-min remained high (R2≥ 0.83). Despite current assumptions around 1-s power, our data shows this relationship is stronger around competition durations, and 1-s power also still shared strong relationships with longer durations out to 20-min. Slopes for relationships shorter durations were closer to a 1:1 relationship than longer durations, but closer to long- duration slopes than to a 1:1 line. The present analyses contradicts both well-accepted hypotheses, and the concept of peak power being a primary metric for sprint cycling, based on very strong relationships to power from durations commonly associated with oxidative energetic pathways, as well as short durations. This study shows the importance and potential of training durations from 1-s to 20-min over a preparation period to improve competition sprint cycling performance.
Zinc nano-fertilization enhances wheat productivity and biofortification
Authors: Yadav Achchhelal , Krishnan Pramila , Kundu Monika , Bana Ram Swaroop , Shaloo  , Choudhary Anil K. , Shivay Y.S. , Meena Samrath Lal , Begam Shbana , Godara Samarth , Ranjan Rajeev , Kumar Sudhir , Yadav Sunita , Nain M.S. , Singh Teekam , Yadav Abhijeet , Raj Rishi
Published: January 2023

Zinc (Zn) malnutrition has emerged as one of the major health challenges in developing nations across the globe. Development of Zn management protocols in staple food crops using modern scientific tools to enhance Zn concentration in grains along with augmented crop yields became utmost necessary. In this context a 2-year experiment was carried out to assess the effects of zinc oxide nanoparticles (ZnO-NPs) vis-à-vis bulk zinc sulfate (ZnSO4) on wheat growth, yield and Zn concentration in plant parts. Four levels of application of ZnO-NPs (0, 20, 25 and 30 mg kg-1) were compared with ZnSO4(equal to Zinc concentration in ZnO-NPs). Results revealed that seed vigor was significantly (p <0.05) higher under 25 and 30 mg kg-1soil ZnO-NPs treatments over ZnSO4. Among the crop yield parameters such as tillers (plant-1), grain weight (plant-1), biomass (plant-1) and grain yield were significantly (p <0.05) higher under ZnO-NPs 25 mg kg-1treated soil as compared to any other treatment. Zinc concentration in grains increased with dose of ZnO-NPs and it was significantly more than ZnSO4treated soil at each treatment level. ZnO-NPs and ZnSO4treatments did not affect photosynthetic rate and chlorophyll (SPAD) content significantly. In conclusion, 25 mg kg-1ZnO-NPs application could be recommended in wheat cultivation to improve growth, yield and grain Zn biofortification.
The possible copepod link between kelp forests, the pelagic ecosystem and deep-sea carbon sequestration
Authors: Kvile Kristina Ø. , Anglès d’Auriac Marc , Altin Dag , Olsen Rolf Erik , Hancke Kasper
Published: January 2023

Kelp forests are dynamic coastal habitats that generate large amounts of carbon-rich detritus. The fate of this detritus is largely unknown and considered a missing link in global carbon budgets. Kelp detritus can serve as food for benthic invertebrates and pelagic invertebrate larvae, but we know close to nothing about the role of kelp detritus as food source for other zooplankton. Lipid-rich pelagic copepods constitute a key link from primary producers to higher trophic levels in marine boreal and arctic ecosystems, and they transport vast amounts of carbon into the deep sea. We conducted feeding experiments to test if the copepodCalanus finmarchicuscan feed on fragments of two dominant kelp species,Saccharina latissimaandLaminaria hyperborea. Such feeding would constitute an undescribed pathway from blue forests to pelagic consumers and deep-sea carbon sequestration. The experiment indicated thatC. finmarchicuscan ingest kelp particles, but the digestion is limited compared to a regular phytoplankton diet. Moreover, the results provide initial evidence thatL. hyperboreacontains substances that are toxic to copepods, an observation that warrants further research. Using specific qPCR assays to trace the consumption of kelp, we found that kelp DNA amplification signals were stronger for copepods fed withS. latissimathan L. hyperborea, but we were not able to conclusively separate consumed kelp from DNA attached to the outside of the copepods.