bluuebunny/crossref_metadata_2025 huggingface dataset:
Refugee Networks, Cooperation, and Resource Access
Authors: MASTERSON DANIEL
Published: November 2023

Without formal avenues for claims-making or political participation, refugees must find their own means of securing services from state and non-state providers. This article asks why some refugee communities are more effective than others in mitigating community problems. I present a framework for understanding how refugees’ social networks shape the constraints and capabilities for collective action. I analyze a field experiment where I organized community meetings with Syrian refugees in Lebanon and Jordan, randomly assigning the recruitment method for meetings to introduce exogenous variation in network structure. During meetings, participants were tasked with resolving collective action problems. I examine the dynamics of subsequent group discussion. Results show that although densely networked refugee groups exhibit more cooperation, they suffer from a resource diversity disadvantage. Group diversity facilitates access to resources that may help refugee communities confront community problems. The novel experimental design allows for separately identifying group-level and individual-level mechanisms.
Resonant excitation of single Kelvin–Helmholtz high-order waves in a magnetized electron fluid vortex
Authors: Maero G. , Panzeri N. , Patricelli L. , Romé M.
Published: November 2023

Thanks to the isomorphism between the drift-Poisson and Euler equations, inviscid two-dimensional fluid experiments can be performed in magnetized, single-component plasmas in Penning–Malmberg traps. Within this analogy, a trapped electron plasma column is equivalent to a two-dimensional vortex. Here, we focus our attention on the generation of V-states, i.e.

$l$

-fold symmetric rotating vorticity patches where the deformation with respect to the circular cross-section has reached the nonlinear regime. We detail a linear theoretical analysis and devise an experimental routine to generate V-states through the precise excitation of single Kelvin–Helmholtz perturbations in a magnetized electron plasma. This technique makes use of suitable multipolar rotating electric fields, which are shown to be able to select the desired wavemode. In particular, with rotating fields, a hardware limitation in the highest accessible mode is removed and nonlinear Kelvin–Helmholtz waves of generic order

$l$

can be attained, which pave the way for further investigations on the evolution and stability properties of V-states. Systematic experimental results for the selective mode growth in the linear and nonlinear regimes up to saturation and collapse are discussed.
Characterization of the complete mitochondrial genomes of the zoonotic parasites Bolbosoma nipponicum and Corynosoma villosum (Acanthocephala: Polymorphida) and the molecular phylogeny of the order Polymorphida
Authors: Li Dai-Xuan , Yang Rui-Jia , Chen Hui-Xia , Kuzmina Tetiana A. , Spraker Terry R. , Li Liang
Published: November 2023

Acanthocephalans of the order Polymorphida mainly parasitic in birds and mammals, are of veterinary, medical and economic importance. However, the evolutionary relationships of its 3 families (Centrorhynchidae, Polymorphidae and Plagiorhynchidae) remain under debate. Additionally, some species of Polymorphida (i.e. Bolbosoma spp. and Corynosoma spp.) are recognized as zoonotic parasites, associated with human acanthocephaliasis, but the mitochondrial genomes for representatives of Bolbosoma and Corynosoma have not been reported so far. In the present study, the complete mitochondrial genomes B. nipponicum and C. villosum (Acanthocephala: Polymorphidae) are reported for the first time, which are 14 296 and 14 241 bp in length, respectively, and both contain 36 genes [including 12 PCGs, 22 tRNA genes and 2 rRNA genes] and 2 non-coding regions (NCR1 and NCR2). The gene arrangement of some tRNAs in the mitogenomes of B. nipponicum and C. villosum differs from that found in all other acanthocephalans, except Polymorphus minutus. Phylogenetic results based on concatenated amino acid (AA) sequences of the 12 protein-coding genes (PCGs) strongly supported that the family Polymorphidae is a sister to the Centrorhynchidae rather than the Plagiorhynchidae, and also confirmed the sister relationship of the genera Bolbosoma and Corynosoma in the Polymorphidae based on the mitogenomic data for the first time. Our present findings further clarified the phylogenetic relationships of the 3 families Plagiorhynchidae, Centrorhynchidae and Polymorphidae, enriched the mitogenome data of the phylum Acanthocephala (especially the order Polymorphida), and provided the resource of genetic data for diagnosing these 2 pathogenic parasites of human acanthocephaliasis.
The design and kinematic representation of a soft robot in a simulation environment
Authors: Emet Hazal , Gür Berke , Dede Mehmet İsmet Can
Published: November 2023

The increase of human presence in the subsea and seabed environments necessitates the development of more capable and highly dexterous, innovative underwater manipulators. Biomimetic soft-robot arms represent a promising candidate for such manipulation systems. However, the well-known modeling techniques and control theories of traditional rigid robots do not apply to soft robots. The challenges of kinematic and dynamic modeling of soft robots with infinite degrees of freedom require the development of dedicated modeling methods. A novel procedure for representing soft-robotic arms and their motion in a rigid-body simulation environment is proposed in this paper. The proposed procedure relies on the piecewise constant curvature approach to simplify the very complex model of hyper-redundant soft-robotic arms, making it suitable for real-time applications. The proposed method is implemented and verified to be used in model-mediated teleoperation of the soft arms of a biomimetic robotic squid designed for underwater manipulation as a case study.
Prevalence and incidence of emergency department presentations and hospital separations with injecting-related infections in a longitudinal cohort of people who inject drugs
Authors: Curtis Stephanie J. , Colledge-Frisby Samantha , Stewardson Andrew J. , Doyle Joseph S. , Higgs Peter , Maher Lisa , Hickman Matthew , Stoové Mark A. , Dietze Paul M.
Published: November 2023

People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31–36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25–30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.
The nutrient profile and cost of specialty dietary patterns: a hypothetical case study
Authors: Lenferna De La Motte Kayla-Anne , Zinn Caryn
Published: November 2023

Objective:

Ketogenic and vegan diets have become increasingly popular. The rising popularity of these dietary trends has been met in kind by the food industry producing a variety of specialty ultra-processed foods (UPF). Despite increasing popularity, the cost and nutrient profile of vegan and ketogenic diets (KD) that rely on UPF specialty products is poorly understood. We aimed to assess the cost and nutrient profile of vegan and KD that relied primarily on UPF and compare this to those that relied primarily on whole foods.

Design:

We designed and calculated the cost of four 1-d meal plans for a hypothetical weight-stable adult female. Two meal plans were created for the vegan-style and ketogenic-style diets, respectively, with one of each being predominantly whole food based and the other constituting primarily of UPF. Carbohydrates were limited to ≤50 g, protein was set at 15–20 % and fat ≥75 % for the ketogenic meal plans. Carbohydrates were set between 45 and 65 %, protein 15 and 25 % and fat 20 and 35 % for the vegan meal plans. FoodWorks dietary analysis software was used to assess data against the national Australian/New Zealand nutrient reference value for adult females and cost was calculated using Countdown online shopping (a local New Zealand supermarket).

Setting:

New Zealand.

Participants:

None.

Results:

The whole food-based meal plans met a greater proportion of the macro and micronutrient thresholds and were less costly when compared with the specialty-based meal plans.

Conclusions:

This study demonstrates that well-planned, predominantly whole food diets (regardless of dietary trend) are nutritionally superior and more cost-effective than those that rely on UPF.
Pain in patients with motor neuron disease: Variation of pain and association with disease severity, health-related quality of life and depression – A longitudinal study
Authors: Spörndly-Nees Sören , Jakobsson Larsson Birgitta , Zetterberg Lena , Åkerblom Ylva , Nyholm Dag , Åsenlöf Pernilla
Published: November 2023

Objectives

To describe levels of pain over time during disease progression in individual patients and for a total sample of patients with motor neuron disease (MND), respectively, and to examine associations between pain, disease severity, health-related quality of life (HRQOL), and depression.

Methods

A prospective cohort study was conducted on 68 patients with MND, including data collected on five occasions over a period of 2 years. Pain was assessed using the Brief Pain Inventory – Short Form. Depression was assessed using the Amyotrophic Lateral Sclerosis (ALS)-Depression-Inventory (ADI-12). Disability progression was measured using the Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised Version (ALSFRS-R). HRQOL was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5).

Results

Participants reported great individual variation over time. The median level of pain was 4 (min 0 and max 10). Higher levels of pain during the last 24 h were associated with higher depression scores (ADI-12), poorer quality of life (ALSAQ-5), and lower reporting of fine and gross motor skills (ALSFRS-R). Baseline pain levels did not predict future values of depression and function. Individuals reporting average pain >3 experienced more hopelessness toward the future and reported higher depression scores compared with participants reporting average pain <3.

Significance of results

Great within-individual variation of pain intensity was reported. Pain intensity was associated with depression, function and HRQOL cross-sectionally, but it did not have a strong prognostic value for future depression, function, or HRQOL. Patients with MND should be offered frequent assessment of pain and depressive symptoms in person-centered care, allowing for individualization of treatment.
A generative model to simulate spatiotemporal dynamics of biomolecules in cells
Authors: Balsollier Lisa , Lavancier Frédéric , Salamero Jean , Kervrann Charles
Published: November 2023

Generators of space-time dynamics in bioimaging have become essential to build ground truth datasets for image processing algorithm evaluation such as biomolecule detectors and trackers, as well as to generate training datasets for deep learning algorithms. In this contribution, we leverage a stochastic model, called birth-death-move (BDM) point process, in order to generate joint dynamics of biomolecules in cells. This particle-based stochastic simulation method is very flexible and can be seen as a generalization of well-established standard particle-based generators. In comparison, our approach allows us: (1) to model a system of particles in motion, possibly in interaction, that can each possibly switch from a motion regime (e.g., Brownian) to another (e.g., a directed motion); (2) to take into account finely the appearance over time of new trajectories and their disappearance, these events possibly depending on the cell regions but also on the current spatial configuration of all existing particles. This flexibility enables to generate more realistic dynamics than standard particle-based simulation procedures, by for example accounting for the colocalization phenomena often observed between intracellular vesicles. We explain how to specify all characteristics of a BDM model, with many practical examples that are relevant for bioimaging applications. As an illustration, based on real fluorescence microscopy datasets, we finally calibrate our model to mimic the joint dynamics of Langerin and Rab11 proteins near the plasma membrane, including the well-known colocalization occurrence between these two types of vesicles. We show that the resulting synthetic sequences exhibit comparable features as those observed in real microscopy image sequences.
VistoSeg: Processing utilities for high-resolution images for spatially resolved transcriptomics data
Authors: Tippani Madhavi , Divecha Heena R. , Catallini Joseph L. , Kwon Sang H. , Weber Lukas M. , Spangler Abby , Jaffe Andrew E. , Hyde Thomas M. , Kleinman Joel E. , Hicks Stephanie C. , Martinowich Keri , Collado-Torres Leonardo , Page Stephanie C. , Maynard Kristen R.
Published: November 2023

Spatially resolved transcriptomics (SRT) is a growing field that links gene expression to anatomical context. SRT approaches that use next-generation sequencing (NGS) combine RNA sequencing with histological or fluorescent imaging to generate spatial maps of gene expression in intact tissue sections. These technologies directly couple gene expression measurements with high-resolution histological or immunofluorescent images that contain rich morphological information about the tissue under study. While broad access to NGS-based spatial transcriptomic technology is now commercially available through the Visium platform from the vendor 10× Genomics, computational tools for extracting image-derived metrics for integration with gene expression data remain limited. We developed VistoSeg as a MATLAB pipeline to process, analyze and interactively visualize the high-resolution images generated in the Visium platform. VistoSeg outputs can be easily integrated with accompanying transcriptomic data to facilitate downstream analyses in common programing languages including R and Python. VistoSeg provides user-friendly tools for integrating image-derived metrics from histological and immunofluorescent images with spatially resolved gene expression data. Integration of this data enhances the ability to understand the transcriptional landscape within tissue architecture. VistoSeg is freely available at http://research.libd.org/VistoSeg/.
A spatial statistical framework for the parametric study of fiber networks: Application to fibronectin deposition by normal and activated fibroblasts
Authors: Grapa Anca-Ioana , Efthymiou Georgios , Van Obberghen-Schilling Ellen , Blanc-Féraud Laure , Descombes Xavier
Published: November 2023

Due to the complex architectural diversity of biological networks, there is an increasing need to complement statistical analyses with a qualitative and local description of their spatial properties. One such network is the extracellular matrix (ECM), a biological scaffold for which changes in its spatial organization significantly impact tissue functions in health and disease. Quantifying variations in the fibrillar architecture of major ECM proteins should considerably advance our understanding of the link between tissue structure and function. Inspired by the analysis of functional magnetic resonance imaging (fMRI) images, we propose a novel statistical analysis approach embedded into a machine learning paradigm, to measure and detect local variations of meaningful ECM parameters. We show that parametric maps representing fiber length and pore directionality can be analyzed within the proposed framework to differentiate among various tissue states. The parametric maps are derived from graph-based representations that reflect the network architecture of fibronectin (FN) fibers in a normal, or disease-mimicking in vitro setting. Such tools can potentially lead to a better characterization of dynamic matrix networks within fibrotic tumor microenvironments and contribute to the development of better imaging modalities for monitoring their remodeling and normalization following therapeutic intervention.
Physical and Chemical Stability of Nanoparticles in Ferrofluid Before and After Impregnation: Implications for Magnetic Pore Fabric Studies
Authors: Biedermann Andrea R. , Mazurek Martin , Schröder Johanna , Arenz Matthias
Published: November 2023

Magnetic pore fabrics (MPFs) are a promising approach to explore the 3D pore space of rocks. There exist empirical relationships between the orientation, degree, and shape of MPF with pore space geometry and permeability anisotropy. Nevertheless, the precise nature of these relationships remains elusive. A common assumption in MPF studies is that ferrofluid uniformly fills the pore space, establishing a constant nanoparticle density and magnetic properties in space and time. However, this assumption is challenged by observations of particle sedimentation and time‐dependent magnetic properties, which render the quantitative interpretation of MPFs challenging. This study explores the physical and chemical stability of ferrofluid, mobility of particles after impregnation, and the magnetic properties of impregnated rocks over time. Water‐based ferrofluids are physically more stable than oil‐based ferrofluids, though with higher magnetic variability. In impregnated rock, magnetic nanoparticles display a certain degree of mobility, resulting in changes in MPF degree and shape. When ferrofluid is mixed with epoxy, particles are less mobile, though some changes were observed both during polymerization and aging. The susceptibility of ferrofluid‐epoxy mixtures is lower than for ferrofluid and carrier liquid at the same concentration. Interestingly, the susceptibility of impregnated rock increases over time, regardless of the ferrofluid used for the impregnation. Understanding and controlling these processes will enhance the reliability of MPF interpretations and increase the applicability of the method.
Mapping Plague Risk Using Super Species Distribution Models and Forecasts for Rodents in the Zhambyl Region, Kazakhstan
Authors: Rametov N. M. , Steiner M. , Bizhanova N. A. , Abdel Z. Zh. , Yessimseit D. T. , Abdeliyev B. Z. , Mussagalieva R. S.
Published: November 2023

One of the most extensive natural plague centers, or foci, is located in Central Asia, in particular, the Zhambyl region in Southern Kazakhstan. Here, we conducted plague surveillance from 2000 to 2020 in the Zhambyl region in Kazakhstan and confirmed 3,072 cases of infected wild animals. We used Species Distribution Modeling by employing MaxEnt, and identified that the natural plague foci are primarily located in the Moiynqum, Betpaqdala, and Tauqum Deserts. The Zhambyl region's central part, including the Moiynqum and Sarysu districts, has a high potential risk of plague outbreak for the rural towns and villages. Since the phenomenon of climate change has been identified as a determinant that affects the rodent populations, thereby elevating the likelihood of an outbreak of plague, we investigated the potential dissemination routes of the disease under the changing climate conditions, thus creating Species Distribution Forecasts for the rodent species in southern part of Kazakhstan for the year 2100. By 2100, in case of increasing temperatures, the range of host species is likely to expand, leading to a higher risk of plague outbreaks. The highest risk of disease transmission can be expected at the outer limits of the modeled total distribution range, where infection rates are high, but antibody presence is low, making many species susceptible to the pathogen. To mitigate the risk of a potential plague outbreak, it is necessary to implement appropriate sanitary‐epidemiological measures and climate mitigation policies.
Time‐Dependent Weakening of Granite at Hydrothermal Conditions
Authors: Jeppson T. N. , Lockner D. A. , Beeler N. M. , Moore D. E.
Published: November 2023

The evolution of a fault's frictional strength during the interseismic period is a critical component of the earthquake cycle, yet there have been relatively few studies that examine the time‐dependent evolution of strength at conditions representative of seismogenic depths. Using a simulated fault in Westerly granite, we examined how frictional strength evolves under hydrothermal conditions up to 250°C during slide‐hold‐slide experiments. At temperatures ≤100°C, frictional strength generally increases with hold duration but, at 200 and 250°C, an initial increase in strength transitions to rapid time‐dependent weakening for holds longer than 14 hr. Forward modeling of long hold periods at 250°C using the rate and state friction constitutive equations requires a second, strongly negative, state variable with a long evolution distance. This implies that significant hydrothermal alteration is occurring at 250°C, consistent with microstructural observations of dissolution and secondary mineral precipitation.
Omphacite Melting and the Destruction of Early High‐Pressure Rock Records
Authors: Liu Shuaiqi , Zhang Guibin , Zhang Lifei , Webb A. Alexander G.
Published: November 2023

The presence of eclogite marks high‐pressure metamorphism and deep, cold burial of crust, and is therefore a widely accepted indicator for the onset of modern‐style plate tectonics. However, eclogite is rarely preserved in many heavily granulite‐overprinted orogens, which are particularly common across ancient metamorphic terranes (i.e., Archean and Paleoproterozoic terranes). Here, we show that eclogite melting processes may be principally responsible for the poor preservation of high‐pressure records. We demonstrate eclogite melting via detailed petrological, geochronological, and geochemical analyses on eclogites and separated centimetric leucosomes from the central Himalaya. The central Himalayan eclogites were overprinted by strong granulite‐facies metamorphism, such that omphacite is only sparsely preserved. Thermodynamic modeling results indicate the eclogite experienced two types of anatectic reactions: phengite dehydration melting at high‐pressure in the presence of omphacite, and subsequent omphacite dominated melting during exhumation. Diagnostic features for these melting reactions include (a) the occurrence of Kfs‐Pl‐Qz multiphase solid inclusions and Cpx‐Pl‐Qz polymineralic inclusions; (b) the high Na2O/K2O melts and Na‐rich plagioclase in leucosomes; (c) the consistent trace elements patterns between omphacite and leucosomes; and (d) obvious Na2O zonation in clinopyroxene. Omphacite dominated melting is characterized by the jadeite breakdown, releasing Na and Al into the melts. This melting mechanism subsequently forms a less sodic clinopyroxene and high Na2O/K2O melts. These Himalayan findings appear relevant to early Earth explorations because of the high thermal gradients and intense granulite‐facies overprints, implying that partial melting of eclogite dominated by omphacite breakdown could have erased early high‐pressure records of modern‐style plate tectonics.
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

The 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

Smart 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

The 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

Many 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

For 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

Estimating 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

Cytoplasmic 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

Understanding 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

Combination 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

Besides 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

The 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

Predicting 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

The 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

Fluorescence 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

Apolipoprotein 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.
EMC rectifies the topology of multipass membrane proteins
Authors: Wu Haoxi , Smalinskaitė Luka , Hegde Ramanujan S.
Published: November 2023

Most eukaryotic multipass membrane proteins are inserted into the membrane of the endoplasmic reticulum. Their transmembrane domains (TMDs) are thought to be inserted co-translationally as they emerge from a membrane-bound ribosome. Here we find that TMDs near the carboxyl terminus of mammalian multipass proteins are inserted post-translationally by the endoplasmic reticulum membrane protein complex (EMC). Site-specific crosslinking shows that the EMC’s cytosol-facing hydrophilic vestibule is adjacent to a pre-translocated C-terminal tail. EMC-mediated insertion is mostly agnostic to TMD hydrophobicity, favored for short uncharged C-tails and stimulated by a preceding unassembled TMD bundle. Thus, multipass membrane proteins can be released by the ribosome–translocon complex in an incompletely inserted state, requiring a separate EMC-mediated post-translational insertion step to rectify their topology, complete biogenesis and evade quality control. This sequential co-translational and post-translational mechanism may apply to ~250 diverse multipass proteins, including subunits of the pentameric ion channel family that are crucial for neurotransmission.