bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal adaptive optics for microscopy through embedded neural network control
Authors: Hu Qi , Hailstone Martin , Wang Jingyu , Wincott Matthew , Stoychev Danail , Atilgan Huriye , Gala Dalia , Chaiamarit Tai , Parton Richard M. , Antonello Jacopo , Packer Adam M. , Davis Ilan , Booth Martin J. 
Published: November 2023

AbstractThe resolution and contrast of microscope imaging is often affected by aberrations introduced by imperfect optical systems and inhomogeneous refractive structures in specimens. Adaptive optics (AO) compensates these aberrations and restores diffraction limited performance. A wide range of AO solutions have been introduced, often tailored to a specific microscope type or application. Until now, a universal AO solution – one that can be readily transferred between microscope modalities – has not been deployed. We propose versatile and fast aberration correction using a physics-based machine learning assisted wavefront-sensorless AO control (MLAO) method. Unlike previous ML methods, we used a specially constructed neural network (NN) architecture, designed using physical understanding of the general microscope image formation, that was embedded in the control loop of different microscope systems. The approach means that not only is the resulting NN orders of magnitude simpler than previous NN methods, but the concept is translatable across microscope modalities. We demonstrated the method on a two-photon, a three-photon and a widefield three-dimensional (3D) structured illumination microscope. Results showed that the method outperformed commonly-used modal-based sensorless AO methods. We also showed that our ML-based method was robust in a range of challenging imaging conditions, such as 3D sample structures, specimen motion, low signal to noise ratio and activity-induced fluorescence fluctuations. Moreover, as the bespoke architecture encapsulated physical understanding of the imaging process, the internal NN configuration was no-longer a “black box”, but provided physical insights on internal workings, which could influence future designs.
Multifunctional transition and temperature-responsive contact lenses
Authors: Salih Ahmed E. , Butt Haider 
Published: November 2023

AbstractSmart contact lenses have recently gained traction due to their functionalization as noninvasive diagnostic and therapeutic wearables that can address several ocular diseases. Herein, multifunctional contact lenses exhibiting UV-transition and temperature-responsive capabilities were developed utilizing chromogenic materials that were integrated simultaneously into poly(2-hydroxyethyl methacrylate) (pHEMA) contact lenses. The functionalities of the contact lenses were optically evaluated in both their activated and non-activated states. Transition contact lenses offered excellent UV and blue light blocking capabilities (~45%) at their inactive states. When activated via UV exposure, the transparent lenses darkened instantaneously and absorbed portions of the visible light spectrum. The absorption intensity and transient discoloration of the transition lenses relied primarily on the utilized photochromic material. Likewise, the temperature-responsive contact lenses exhibited distinct colorimetric variations in response to temperature changes within the physiological range (33–38 °C). The maximum sensitivity of the thermochromic lens was 8% transmitted light per Celsius degree shift. Physiochemical and morphological analysis indicated the adequacy of the contact lenses. Hence, the multifunctional contact lenses can be deployed as smart wearables to manage ophthalmic deficiencies that are deterred by UV radiations and variations in ocular surface temperature.
Unistrand piRNA clusters are an evolutionarily conserved mechanism to suppress endogenous retroviruses across the Drosophila genus
Authors: van Lopik Jasper , Alizada Azad , Trapotsi Maria-Anna , Hannon Gregory J. , Bornelöv Susanne , Czech Nicholson Benjamin 
Published: November 2023

AbstractThe PIWI-interacting RNA (piRNA) pathway prevents endogenous genomic parasites, i.e. transposable elements, from damaging the genetic material of animal gonadal cells. Specific regions in the genome, called piRNA clusters, are thought to define each species’ piRNA repertoire and therefore its capacity to recognize and silence specific transposon families. The unistrand cluster flamenco (flam) is essential in the somatic compartment of the Drosophila ovary to restrict Gypsy-family transposons from infecting the neighbouring germ cells. Disruption of flam results in transposon de-repression and sterility, yet it remains unknown whether this silencing mechanism is present more widely. Here, we systematically characterise 119 Drosophila species and identify five additional flam-like clusters separated by up to 45 million years of evolution. Small RNA-sequencing validated these as bona-fide unistrand piRNA clusters expressed in somatic cells of the ovary, where they selectively target transposons of the Gypsy family. Together, our study provides compelling evidence of a widely conserved transposon silencing mechanism that co-evolved with virus-like Gypsy-family transposons.
A fish cartel for Africa
Authors: Englander Gabriel , Costello Christopher 
Published: November 2023

AbstractMany countries sell fishing rights to foreign nations and fishers. Although African coastal waters are among the world’s most biologically rich, African countries earn much less than their peers from selling access to foreign fishers. African countries sell fishing access individually (in contrast to some Pacific countries who sell access as a bloc). We develop a bilateral oligopoly model to simulate the effects of an African fish cartel. The model shows that wielding market power entails both ecological and economic dimensions. Africa would substantially restrict access catch, which raises biomass by 16%. But this also confers economic benefits to all African nations, raising profits by an average of 23%. These benefits arise because market power shifts from foreign buyers to African sellers. While impediments to sustainable development like corruption are hard to change in the medium-term, deeper African integration is an already-emerging solution to African countries’ economic and ecological challenges.
Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly
Authors: Goellner Sarah , Enkavi Giray , Prasad Vibhu , Denolly Solène , Eu Sungmin , Mizzon Giulia , Witte Leander , Kulig Waldemar , Uckeley Zina M. , Lavacca Teresa M. , Haselmann Uta , Lozach Pierre-Yves , Brügger Britta , Vattulainen Ilpo , Bartenschlager Ralf 
Published: November 2023

AbstractFor successful infection of host cells and virion production, enveloped viruses, including Zika virus (ZIKV), extensively rely on cellular lipids. However, how virus protein–lipid interactions contribute to the viral life cycle remains unclear. Here, we employ a chemo-proteomics approach with a bifunctional cholesterol probe and show that cholesterol is closely associated with the ZIKV structural protein prM. Bioinformatic analyses, reverse genetics alongside with photoaffinity labeling assays, and atomistic molecular dynamics simulations identified two functional cholesterol binding motifs within the prM transmembrane domain. Loss of prM–cholesterol association has a bipartite effect reducing ZIKV entry and leading to assembly defects. We propose a model in which membrane-resident M facilitates cholesterol-supported lipid exchange during endosomal entry and, together with cholesterol, creates a platform promoting virion assembly. In summary, we identify a bifunctional role of prM in the ZIKV life cycle by mediating viral entry and virus assembly in a cholesterol-dependent manner.
Impact of vaccinations, boosters and lockdowns on COVID-19 waves in French Polynesia
Authors: Chapman Lloyd A. C. , Aubry Maite , Maset Noémie , Russell Timothy W. , Knock Edward S. , Lees John A. , Mallet Henri-Pierre , Cao-Lormeau Van-Mai , Kucharski Adam J. 
Published: November 2023

AbstractEstimating the impact of vaccination and non-pharmaceutical interventions on COVID-19 incidence is complicated by several factors, including successive emergence of SARS-CoV-2 variants of concern and changing population immunity from vaccination and infection. We develop an age-structured multi-strain COVID-19 transmission model and inference framework to estimate vaccination and non-pharmaceutical intervention impact accounting for these factors. We apply this framework to COVID-19 waves in French Polynesia and estimate that the vaccination programme averted 34.8% (95% credible interval: 34.5–35.2%) of 223,000 symptomatic cases, 49.6% (48.7–50.5%) of 5830 hospitalisations and 64.2% (63.1–65.3%) of 1540 hospital deaths that would have occurred in a scenario without vaccination up to May 2022. We estimate the booster campaign contributed 4.5%, 1.9%, and 0.4% to overall reductions in cases, hospitalisations, and deaths. Our results suggest that removing lockdowns during the first two waves would have had non-linear effects on incidence by altering accumulation of population immunity. Our estimates of vaccination and booster impact differ from those for other countries due to differences in age structure, previous exposure levels and timing of variant introduction relative to vaccination, emphasising the importance of detailed analysis that accounts for these factors.
Copy number variation of the restorer Rf4 underlies human selection of three-line hybrid rice breeding
Authors: Zhao Zhe , Ding Zhi , Huang Jingjing , Meng Hengjun , Zhang Zixu , Gou Xin , Tang Huiwu , Xie Xianrong , Ping Jingyao , Xiao Fangming , Liu Yao-Guang , Xie Yongyao , Chen Letian 
Published: November 2023

AbstractCytoplasmic male sterility (CMS) lines are important for breeding hybrid crops, and utilization of CMS lines requires strong fertility restorer (Rf) genes. Rf4, a major Rf for Wild-Abortive CMS (CMS-WA), has been cloned in rice. However, the Rf4 evolution and formation of CMS-WA/Rf system remain elusive. Here, we show that the Rf4 locus emerges earlier than the CMS-WA gene WA352 in wild rice, and 69 haplotypes of the Rf4 locus are generated in the Oryza genus through the copy number and sequence variations. Eight of these haplotypes of the Rf4 locus are enriched in modern rice cultivars during natural and human selections, whereas non-functional rf4i is preferentially selected for breeding current CMS-WA lines. We further verify that varieties carrying two-copy Rf4 haplotype have stronger fertility restoration ability and are widely used in three-line hybrid rice breeding. Our findings increase our understanding of CMS/Rf systems and will likely benefit crop breeding.
The Imageable Genome
Authors: Jané Pablo , Xu Xiaoying , Taelman Vincent , Jané Eduardo , Gariani Karim , Dumont Rebecca A. , Garama Yonathan , Kim Francisco , del Val Gomez María , Walter Martin A. 
Published: November 2023

AbstractUnderstanding human disease on a molecular level, and translating this understanding into targeted diagnostics and therapies are central tenets of molecular medicine1. Realizing this doctrine requires an efficient adaptation of molecular discoveries into the clinic. We present an approach to facilitate this process by describing the Imageable Genome, the part of the human genome whose expression can be assessed via molecular imaging. Using a deep learning-based hybrid human-AI pipeline, we bridge individual genes and their relevance in human diseases with specific molecular imaging methods. Cross-referencing the Imageable Genome with RNA-seq data from over 60,000 individuals reveals diagnostic, prognostic and predictive imageable genes for a wide variety of major human diseases. Having both the critical size and focus to be altered in its expression during the development and progression of any human disease, the Imageable Genome will generate new imaging tools that improve the understanding, diagnosis and management of human diseases.
A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics
Authors: Lee Hyeong-Min , Wright William C. , Pan Min , Low Jonathan , Currier Duane , Fang Jie , Singh Shivendra , Nance Stephanie , Delahunty Ian , Kim Yuna , Chapple Richard H. , Zhang Yinwen , Liu Xueying , Steele Jacob A. , Qi Jun , Pruett-Miller Shondra M. , Easton John , Chen Taosheng , Yang Jun , Durbin Adam D. , Geeleher Paul 
Published: November 2023

AbstractCombination chemotherapy is crucial for successfully treating cancer. However, the enormous number of possible drug combinations means discovering safe and effective combinations remains a significant challenge. To improve this process, we conduct large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritize neuroblastoma, the most common extracranial pediatric solid tumor, where ~50% of high-risk patients do not survive. Our screen examines all druggable gene knockouts in 18 cell lines (10 neuroblastoma, 8 others) treated with 8 widely used drugs, resulting in 94,320 unique combination-cell line perturbations, which is comparable to the largest existing drug combination screens. Using dense drug-drug rescreening, we find that the top CRISPR-nominated drug combinations are more synergistic than standard-of-care combinations, suggesting existing combinations could be improved. As proof of principle, we discover that inhibition of PRKDC, a component of the non-homologous end-joining pathway, sensitizes high-risk neuroblastoma cells to the standard-of-care drug doxorubicin in vitro and in vivo using patient-derived xenograft (PDX) models. Our findings provide a valuable resource and demonstrate the feasibility of using targeted CRISPR knockout to discover combinations with common chemotherapeutics, a methodology with application across all cancers.
Functional and structural diversity in deubiquitinases of the Chlamydia-like bacterium Simkania negevensis
Authors: Boll Vanessa , Hermanns Thomas , Uthoff Matthias , Erven Ilka , Hörner Eva-Maria , Kozjak-Pavlovic Vera , Baumann Ulrich , Hofmann Kay 
Published: November 2023

AbstractBesides the regulation of many cellular pathways, ubiquitination is important for defense against invading pathogens. Some intracellular bacteria have evolved deubiquitinase (DUB) effector proteins, which interfere with the host ubiquitin system and help the pathogen to evade xenophagy and lysosomal degradation. Most intracellular bacteria encode one or two DUBs, which are often linkage-promiscuous or preferentially cleave K63-linked chains attached to bacteria or bacteria-containing vacuoles. By contrast, the respiratory pathogen Legionella pneumophila possesses a much larger number of DUB effectors, including a K6-specific enzyme belonging to the OTU family and an M1-specific DUB uniquely found in this bacterium. Here, we report that the opportunistic pathogen Simkania negevensis, which is unrelated to Legionella but has a similar lifestyle, encodes a similarly large number of DUBs, including M1- and K6-specific enzymes. Simkania DUBs are highly diverse and include DUB classes never before seen in bacteria. Interestingly, the M1- and K6-specific DUBs of Legionella and Simkania are unrelated, suggesting that their acquisition occurred independently. We characterize the DUB activity of eight Simkania-encoded enzymes belonging to five different DUB classes. We also provide a structural basis for the M1-specificity of a Simkania DUB, which most likely evolved from a eukaryotic otubain-like precursor.
NAD+ regulates nucleotide metabolism and genomic DNA replication
Authors: Munk Sebastian Howen Nesgaard , Merchut-Maya Joanna Maria , Adelantado Rubio Alba , Hall Arnaldur , Pappas George , Milletti Giacomo , Lee MyungHee , Johnsen Lea Giørtz , Guldberg Per , Bartek Jiri , Maya-Mendoza Apolinar 
Published: November 2023

AbstractThe intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb’s cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb’s cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy.
Forecasting the dynamics of a complex microbial community using integrated meta-omics
Authors: Delogu Francesco , Kunath Benoit J. , Queirós Pedro M. , Halder Rashi , Lebrun Laura A. , Pope Phillip B. , May Patrick , Widder Stefanie , Muller Emilie E. L. , Wilmes Paul 
Published: November 2023

AbstractPredicting the behaviour of complex microbial communities is challenging. However, this is essential for complex biotechnological processes such as those in biological wastewater treatment plants (BWWTPs), which require sustainable operation. Here we summarize 14 months of longitudinal meta-omics data from a BWWTP anaerobic tank into 17 temporal signals, explaining 91.1% of the temporal variance, and link those signals to ecological events within the community. We forecast the signals over the subsequent five years and use 21 extra samples collected at defined time intervals for testing and validation. Our forecasts are correct for six signals and hint on phenomena such as predation cycles. Using all the 17 forecasts and the environmental variables, we predict gene abundance and expression, with a coefficient of determination ≥0.87 for the subsequent three years. Our study demonstrates the ability to forecast the dynamics of open microbial ecosystems using interactions between community cycles and environmental parameters.
Volatile methyl jasmonate from roots triggers host-beneficial soil microbiome biofilms
Authors: Kulkarni Omkar S. , Mazumder Mrinmoy , Kini Shruthi , Hill Eric D. , Aow Johanan Shao Bing , Phua Samantha Mun Lin , Elejalde Untzizu , Kjelleberg Staffan , Swarup Sanjay 
Published: November 2023

AbstractThe rhizosphere is a niche surrounding plant roots, where soluble and volatile molecules mediate signaling between plants and the associated microbiota. The preferred lifestyle of soil microorganisms is in the form of biofilms. However, less is known about whether root volatile organic compounds (rVOCs) can influence soil biofilms beyond the 2–10 mm rhizosphere zone influenced by root exudates. We report that rVOCs shift the microbiome composition and growth dynamics of complex soil biofilms. This signaling is evolutionarily conserved from ferns to higher plants. Methyl jasmonate (MeJA) is a bioactive signal of rVOCs that rapidly triggers both biofilm and microbiome changes. In contrast to the planktonic community, the resulting biofilm community provides ecological benefits to the host from a distance via growth enhancement. Thus, a volatile host defense signal, MeJA, is co-opted for assembling host-beneficial biofilms in the soil microbiota and extending the sphere of host influence in the rhizosphere.
Bio-friendly long-term subcellular dynamic recording by self-supervised image enhancement microscopy
Authors: Zhang Guoxun , Li Xiaopeng , Zhang Yuanlong , Han Xiaofei , Li Xinyang , Yu Jinqiang , Liu Boqi , Wu Jiamin , Yu Li , Dai Qionghai 
Published: November 2023

AbstractFluorescence microscopy has become an indispensable tool for revealing the dynamic regulation of cells and organelles. However, stochastic noise inherently restricts optical interrogation quality and exacerbates observation fidelity when balancing the joint demands of high frame rate, long-term recording and low phototoxicity. Here we propose DeepSeMi, a self-supervised-learning-based denoising framework capable of increasing signal-to-noise ratio by over 12 dB across various conditions. With the introduction of newly designed eccentric blind-spot convolution filters, DeepSeMi effectively denoises images with no loss of spatiotemporal resolution. In combination with confocal microscopy, DeepSeMi allows for recording organelle interactions in four colors at high frame rates across tens of thousands of frames, monitoring migrasomes and retractosomes over a half day, and imaging ultra-phototoxicity-sensitive Dictyostelium cells over thousands of frames. Through comprehensive validations across various samples and instruments, we prove DeepSeMi to be a versatile and biocompatible tool for breaking the shot-noise limit.
The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegeneration and neuroinflammation
Authors: Nelson Maxine R. , Liu Peng , Agrawal Ayushi , Yip Oscar , Blumenfeld Jessica , Traglia Michela , Kim Min Joo , Koutsodendris Nicole , Rao Antara , Grone Brian , Hao Yanxia , Yoon Seo Yeon , Xu Qin , De Leon Samuel , Choenyi Tenzing , Thomas Reuben , Lopera Francisco , Quiroz Yakeel T. , Arboleda-Velasquez Joseph F. , Reiman Eric M. , Mahley Robert W. , Huang Yadong 
Published: November 2023

AbstractApolipoprotein E4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD), leading to earlier age of clinical onset and exacerbating pathologies. There is a critical need to identify protective targets. Recently, a rare APOE variant, APOE3-R136S (Christchurch), was found to protect against early-onset AD in a PSEN1-E280A carrier. In this study, we sought to determine if the R136S mutation also protects against APOE4-driven effects in LOAD. We generated tauopathy mouse and human iPSC-derived neuron models carrying human APOE4 with the homozygous or heterozygous R136S mutation. We found that the homozygous R136S mutation rescued APOE4-driven Tau pathology, neurodegeneration and neuroinflammation. The heterozygous R136S mutation partially protected against APOE4-driven neurodegeneration and neuroinflammation but not Tau pathology. Single-nucleus RNA sequencing revealed that the APOE4-R136S mutation increased disease-protective and diminished disease-associated cell populations in a gene dose-dependent manner. Thus, the APOE-R136S mutation protects against APOE4-driven AD pathologies, providing a target for therapeutic development against AD.