bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerically quantifying the spectral dependence of the absorption enhancement of partially-coated black carbon with complex microphysical properties
Authors: Luo Jie , Hu Miao , Luo Jianfei , Li Congcong , Bi Meihua , Zhou Xuefang , Geng Xiulin , Wu Chao , Li Kaitao , Wang Feng
Published: December 2024

The absorption of black carbon (BC) will be enhanced after it is coated with other components, and the research on the enhancement of BC absorption has become a hot topic in climate research in recent years. Some studies have measured the enhancement of BC absorption in certain specific wavelengths, and these measurement results are often used for the analysis of absorption in other wavelengths as well. This work employs numerical methods to quantitatively study the impact of microphysical characteristics of BC with non-absorbing coating on its spectral characteristics of absorption enhancement. This study defines the absorption enhancement Ångström exponent (EABSAE) to quantitatively describe the spectral characteristics of BC absorption enhancement. There are certain differences in the trends of absorption enhancement in different wavelengths with respect to microphysical characteristics, and EABSAE may deviate significantly from 0. The EABSAE of spherical BC usually varies between -2.5 and 2 in the wavelength range of 440–1064 nm. When considering the influence of complex morphology, the statistically average EABSAE of BC assembles with typical particle size distribution is roughly between -2 and 3. In the atmosphere, brown carbon (BrC) can mix with BC, which makes the EABSAE more complex. The EABSAE of BC coated with BrC can have a higher value. Therefore, an EABSAE value of at least 3 is required to prove the existence of BrC. In addition, the uncertainty in the calculation of absorption at other wavelengths was also evaluated in this work based on the absorption enhancement at a given wavelength.
Observation of single-photon azimuthal backflow with weak measurement
Authors: Zhang Zhen-Fei , Huang Peng-Fei , Dong Shan-Chuan , Rong Yan-Xin , Xu Jin-Shi , Gu Yong-Jian , Xiao Ya
Published: December 2024

Quantum backflow (QB), a counterintuitive interference phenomenon where particles with positive momentum can propagate backward, is important in applications involving light–matter interactions. To date, experimental demonstrations of backflow have been restricted to classical optical systems using techniques such as slit scanning or Shack–Hartmann wavefront sensing, which suffer from low spatial resolution due to the inherent limitations in slit width and lenslet array density. Here, we report an observation of azimuthal backflow (AB) both theoretically and experimentally by employing the weak measurement technique, which enables the precise extraction of photon momentum at each pixel. Our results show that a heralded single photon, prepared in specific superposition states with solely negative orbital angular momentum (OAM), can exhibit positive OAM. The effects of mode ratio, propagation distance, and OAM index on the azimuthal backflow are systematically investigated. This work provides new techniques for observing and manipulating backflow in quantum systems.
Concatenation of Kerr solitary waves in ceramic YAG: application to coherent Raman imaging
Authors: Bagley N. , Wehbi S. , Mansuryan T. , Boulesteix R. , Maître A. , Arosa Lobato Y. , Ferraro M. , Mangini F. , Sun Y. , Krupa K. , Wetzel B. , Couderc V. , Wabnitz S. , Aceves A. , Tonello A.
Published: December 2024

A coherent concatenation of multiple solitary waves may lead to a
stable infrared and visible broadband filament in a ceramic YAG
polycrystal. This self-trapped soliton train is leveraged to implement
self-referenced multiplex coherent anti-Stokes Raman scattering
(SR-M-CARS) imaging. Simulations and experiments illustrating the
filamentation process and the concatenation of focusing–defocusing
cycles in ceramic and crystal YAG are presented. In addition, our
simulations and experiments further examine the dependence of the
filamentation onset location and supercontinuum (SC) generation upon
peak input power. Understanding this dependence is key for the
implementation of viable CARS imaging techniques, due to the
comparatively exceptional ability of YAG to generate supercontinuum
that can enable higher-sensitivity imaging without delay lines.
V-shaped PSF for 3D imaging over an extended depth of field in wide-field microscopy
Authors: Li Yunyang , Zhang Zixiao , Tian Feng , Luna-Palacios Yryx Y. , Rocha-Mendoza Israel , Yang Weijian
Published: December 2024

Single-shot 3D optical microscopy that can capture high-resolution
information over a large volume has broad applications in biology.
Existing 3D imaging methods using point-spread-function (PSF)
engineering often have limited depth of field (DOF) or require custom
and often complex design of phase masks. We propose a new, to the best
of our knowledge, PSF approach that is easy to implement and offers a
large DOF. The PSF appears to be axially V-shaped, engineered by
replacing the conventional tube lens with a pair of axicon lenses
behind the objective lens of a wide-field microscope. The 3D
information can be reconstructed from a single-shot image using a deep
neural network. Simulations in a 10× magnification wide-field
microscope show the V-shaped PSF offers excellent 3D resolution
(<2.5 µm lateral and ∼15 µm
axial) over a ∼350 µm DOF at a 550 nm
wavelength. Compared to other popular PSFs designed for 3D imaging,
the V-shaped PSF is simple to deploy and provides high 3D
reconstruction quality over an extended DOF.
High-security physical layer encryption scheme for dual-mode index modulation-aided OFDM in magnetic induction communication
Authors: Wang Jiyuan , Liu Bo , Ren Jianxin , Chen Shuaidong , Gan Zhushan , Mao Yaya , Song Xiumin , Wu Xiangyu , Wang Feng , Sun Tingting
Published: December 2024

A high security physical layer encryption scheme for dual-mode orthogonal frequency division multiplexing with index modulation (DM-OFDM-IM) in magnetic induction communication is proposed. The scheme utilizes DM-OFDM-IM, where subcarriers within each subblock are divided into two groups, each modulated by distinct signal constellations. DM-OFDM-IM leverages the sequential information from the modulated constellation to transmit extra information, leading to a substantial enhancement in spectral efficiency. In order to improve the security of DM-OFDM-IM magnetic communication system, a 4D hyperchaos model is used to generate four columns of chaotic sequences for specific encryption, frequencies, and symbols scrambling of transmitted data to prevent attacks from illegal receivers. A DM-OFDM-IM magnetic communication signal encrypted by 23.76 kb/s is experimentally transmitted on a 36 cm magnetic induction coil. Due to the use of geometric shaping, the communication distance is increased by 0.316 cm compared with the traditional 8QAM modulation at the hard-decision FEC BER limit of 3.8 × 10−3. The experimental results show that the bit error rate (BER) performance of the signal before and after encryption does not significantly differ. In addition, the key space of the scheme can reach 10146, which effectively ensures the physical layer security of the system. This approach offers robust performance and enhanced security, making it a promising solution for short-distance magnetic communication applications.
Generalized Stokes polarimetry design for a 3-D polarization field
Authors: Wang Luo , Peng Yue , Zhang Haiyang , Zhao Changming
Published: December 2024

Optical polarization is three-dimensional (3-D). Its complete information is described by the nine-component generalized Stokes vector (GSV). However, existing Stokes polarimetry and its design theory are primarily based on the paraxial four-component Stokes vector and 4 × 4 Mueller matrices. In this Letter, we introduce a novel concept of generalized Stokes polarimetry (GSP), which can reconstruct nine generalized Stokes parameters through a series of non-paraxial polarized modulations and intensity projections. The reconstruction theory of GSP is based on the 9 × 9 generalized Mueller matrix (GMM) calculator we reported previously. In addition, to optimize the 9 × 9 analysis matrix of GSP, we developed an optimization algorithm combined Monte Carlo and gradient descent (GD) methods, finding the optimal configuration with CN = 3.7261 and EWV = 1.2405. The simulated results of noise sources and GSV reconstruction verified the significant improvement in accuracy and stability of optimized configuration.
Nonlinear switch and spatial lattice solitons of photonic s–p orbitals
Authors: Rajeevan Gayathry , Mukherjee Sebabrata
Published: December 2024

We develop fs laser-fabricated asymmetric couplers and zig-zag arrays consisting of single- and two-mode waveguides with bipartite Kerr nonlinearity in borosilicate (BK7) glass substrates. The fundamental mode (s orbital) is near resonance with the neighboring higher-order p orbital, causing efficient light transfer at low power. Due to Kerr nonlinearity, the coupler works as an all-optical switch between s and p orbitals. Single- and double-peak spatial lattice solitons of s–p orbitals form due to the bipartite nature of the on-site nonlinearity. We probe highly localized bulk and edge solitons, peaked at the s and p orbitals, spectrally residing in the photonic bandgap. Our work will be important for exploring inter-orbital couplings and nonlinear interactions in intricate photonic devices.
Mid-infrared Fourier ptychographic upconversion imaging
Authors: Zheng Tingting , Wei Zhuohang , Huang Kun , Yu Mengyao , Fang Jianan , Wen Zhaoyang , Zhang Jixi , Zeng Heping
Published: December 2024

The frequency upconversion technique offers an appealing approach for sensitive mid-infrared (MIR) imaging at room temperature. However, the spatial resolution of the upconversion imager has been notoriously restricted by the limited transverse section of the involved nonlinear crystal at the Fourier plane. Here, we implement a wide-field and high-resolution MIR upconversion imaging system based on elliptical pumping and Fourier ptychography. Specifically, an elliptical pump beam is engineered to accommodate the narrow aperture of chirped-poling crystals, thus facilitating the acquisition of high-spatial-frequency components in the lateral direction. Such an elliptical passband in the Fourier space is then discretely rotated to generate a sequence of upconversion images, which allows computational recovery of a high-resolution object image through a combination of synthetic aperture and phase retrieval operations. Consequently, an enhanced spatial resolution of 39 µm is achieved within a field of view about 25 mm, which corresponds to a space-bandwidth product of 3.2×105, over tenfold larger than previously demonstrated values. Moreover, the MIR upconversion imager can operate under a low-light illumination of one photon/pulse/pixel. Therefore, the presented paradigm of nonlinear Fourier ptychography paves the way toward high-throughput infrared imaging with massive resolvable elements and single-photon sensitivity, which would stimulate a variety of applications such as industry inspection and biomedical diagnosis.
Meta-analysis of single-cell RNA sequencing co-expression in human neural organoids reveals their high variability in recapitulating primary tissue
Authors: Werner Jonathan M. , Gillis Jesse
Published: December 2024

Human neural organoids offer an exciting opportunity for studying inaccessible human-specific brain development; however, it remains unclear how precisely organoids recapitulate fetal/primary tissue biology. We characterize field-wide replicability and biological fidelity through a meta-analysis of single-cell RNA-sequencing data for first and second trimester human primary brain (2.95 million cells, 51 data sets) and neural organoids (1.59 million cells, 173 data sets). We quantify the degree primary tissue cell type marker expression and co-expression are recapitulated in organoids across 10 different protocol types. By quantifying gene-level preservation of primary tissue co-expression, we show neural organoids lie on a spectrum ranging from virtually no signal to co-expression indistinguishable from primary tissue, demonstrating a high degree of variability in biological fidelity among organoid systems. Our preserved co-expression framework provides cell type-specific measures of fidelity applicable to diverse neural organoids, offering a powerful tool for uncovering unifying axes of variation across heterogeneous neural organoid experiments.
Temperature cues are integrated in a flexible circadian neuropeptidergic feedback circuit to remodel sleep-wake patterns in flies
Authors: Yuan Xin , Li Hailiang , Guo Fang
Published: December 2024

Organisms detect temperature signals through peripheral neurons, which relay them to central circadian networks to drive adaptive behaviors. Despite recent advances in Drosophila research, how circadian circuits integrate temperature cues with circadian signals to regulate sleep/wake patterns remains unclear. In this study, we used the FlyWire brain electron microscopy connectome to map neuronal connections, identifying lateral posterior neurons LPNs as key nodes for integrating temperature information into the circadian network. LPNs receive input from both circadian and temperature-sensing neurons, promoting sleep behavior. Through connectome analysis, genetic manipulation, and behavioral assays, we demonstrated that LPNs, downstream of thermo-sensitive anterior cells (ACs), suppress activity-promoting lateral dorsal neurons LNds via the AstC pathway, inducing sleep Disrupting LPN-LNd communication through either AstCR1 RNAi in LNds or in an AstCR1 mutant significantly impairs the heat-induced reduction in the evening activity peak. Conversely, optogenetic calcium imaging and behavioral assays revealed that cold-activated LNds subsequently stimulate LPNs through NPF-NPFR signaling, establishing a negative feedback loop. This feedback mechanism limits LNd activation to appropriate levels, thereby fine-tuning the evening peak increase at lower temperatures. In conclusion, our study constructed a comprehensive connectome centered on LPNs and identified a novel peptidergic circadian feedback circuit that coordinates temperature and circadian signals, offering new insights into the regulation of sleep patterns in Drosophila.
Bacterial TonB-dependent transducers interact with the anti-σ factor in absence of the inducing signal protecting it from proteolysis
Authors: Wettstadt Sarah , Marcos-Torres Francisco J. , Otero-Asman Joaquín R. , García-Puente Alicia , Ortega Álvaro , Llamas María A.
Published: December 2024

Competitive bacteria like the human pathogen Pseudomonas aeruginosa can acquire iron from different iron carriers, which are usually internalized via outer membrane TonB-dependent receptors (TBDRs). Production of TBDRs is promoted by the presence of the substrate. This regulation often entails a signal transfer pathway known as cell-surface signaling (CSS) that involves the TBDR itself that also functions as transducer (and is thus referred to as TBDT), a cytoplasmic membrane-bound anti-σ factor, and an extracytoplasmic function σ (σECF) factor. TBDTs contain an extra N-terminal domain known as signaling domain (SD) required for the signal transfer activity of these receptors. In the current CSS model, presence of the signal allows the interaction between the TBDT and the anti-σ factor in the periplasm, promoting the proteolysis of the anti-σ factor and in turn the σECF-dependent transcription of response genes, including the TBDT gene. However, recent evidence shows that σECF activity does not depend on this interaction, suggesting that the contact between these 2 proteins fulfills a different role. Using the P. aeruginosa Fox CSS system as model, we show here that the SD of the FoxA TBDT already interacts with the C-terminal domain of the FoxR anti-σ factor in absence of the signal. This interaction protects FoxR from proteolysis in turn preventing transcription of σFoxI-dependent genes. By structural modeling of the FoxR/FoxASD interaction, we have identified the interaction sites between these 2 proteins and provide the molecular details of this interaction. We furthermore show that to exert this protective role, FoxA undergoes proteolytic cleavage, denoting a change in the paradigm of the current CSS model.
A chromosomal mutation is superior to a plasmid-encoded mutation for plasmid fitness cost compensation
Authors: Wright Rosanna C. T. , Wood A. Jamie , Bottery Michael J. , Muddiman Katie J. , Paterson Steve , Harrison Ellie , Brockhurst Michael A. , Hall James P. J.
Published: December 2024

Plasmids are important vectors of horizontal gene transfer in microbial communities but can impose a burden on the bacteria that carry them. Such plasmid fitness costs are thought to arise principally from conflicts between chromosomal- and plasmid-encoded molecular machineries, and thus can be ameliorated by compensatory mutations (CMs) that reduce or resolve the underlying causes. CMs can arise on plasmids (i.e., plaCM) or on chromosomes (i.e., chrCM), with contrasting predicted effects upon plasmid success and subsequent gene transfer because plaCM can also reduce fitness costs in plasmid recipients, whereas chrCM can potentially ameliorate multiple distinct plasmids. Here, we develop theory and a novel experimental system to directly compare the ecological effects of plaCM and chrCM that arose during evolution experiments between Pseudomonas fluorescens SBW25 and its sympatric mercury resistance megaplasmid pQBR57. We show that while plaCM was predicted to succeed under a broader range of parameters in mathematical models, chrCM dominated in our experiments, including conditions with numerous recipients, due to a more efficacious mechanism of compensation, and advantages arising from transmission of costly plasmids to competitors (plasmid “weaponisation”). We show analytically the presence of a mixed Rock-Paper-Scissors (RPS) regime for CMs, driven by trade-offs with horizontal transmission, that offers one possible explanation for the observed failure of plaCM to dominate even in competition against an uncompensated plasmid. Our results reveal broader implications of plasmid-bacterial evolution for plasmid ecology, demonstrating the importance of specific compensatory mutations for resistance gene spread. One consequence of the superiority of chrCM over plaCM is the likely emergence in microbial communities of compensated bacteria that can act as “hubs” for plasmid accumulation and dissemination.
Intracellular polarization of RNAs and proteins in the human small intestinal epithelium
Authors: Novoselsky Roy , Harnik Yotam , Yakubovsky Oran , Katina Corine , Levin Yishai , Bahar Halpern Keren , Pencovich Niv , Nachmany Ido , Itzkovitz Shalev
Published: December 2024

The intestinal epithelium is a polarized monolayer of cells, with an apical side facing the lumen and a basal side facing the blood stream. In mice, both proteins and mRNAs have been shown to exhibit global basal-apical polarization; however, polarization in the human intestine has not been systematically explored. Here, we employed laser-capture microdissection to isolate apical and basal epithelial segments from intestinal tissues of 8 individuals and performed RNA sequencing and mass-spectrometry proteomics. We find a substantial polarization of mRNA molecules that largely overlaps polarization patterns observed in mice. This mRNA polarization remains consistent across different zones of the intestinal villi and is generally correlated with the polarization of proteins. Our protein analysis exposes streamlined intracellular nutrient transport and processing and reveals that mitochondria and ribosomes are less polarized in humans compared to mice. Our study provides a resource for understanding human intestinal epithelial biology.
Parallel development of object recognition in newborn chicks and deep neural networks
Authors: Pandey Lalit , Lee Donsuk , Wood Samantha M. W. , Wood Justin N.
Published: December 2024

How do newborns learn to see? We propose that visual systems are space-time fitters, meaning visual development can be understood as a blind fitting process (akin to evolution) in which visual systems gradually adapt to the spatiotemporal data distributions in the newborn’s environment. To test whether space-time fitting is a viable theory for learning how to see, we performed parallel controlled-rearing experiments on newborn chicks and deep neural networks (DNNs), including CNNs and transformers. First, we raised newborn chicks in impoverished environments containing a single object, then simulated those environments in a video game engine. Second, we recorded first-person images from agents moving through the virtual animal chambers and used those images to train DNNs. Third, we compared the viewpoint-invariant object recognition performance of the chicks and DNNs. When DNNs received the same visual diet (training data) as chicks, the models developed common object recognition skills as chicks. DNNs that used time as a teaching signal—space-time fitters—also showed common patterns of successes and failures across the test viewpoints as chicks. Thus, DNNs can learn object recognition in the same impoverished environments as newborn animals. We argue that space-time fitters can serve as formal scientific models of newborn visual systems, providing image-computable models for studying how newborns learn to see from raw visual experiences.
Social conformity is a heuristic when individual risky decision-making is disrupted
Authors: Orloff Mark A. , Chung Dongil , Gu Xiaosi , Wang Xingchao , Gao Zhixian , Song Guiding , Tatineni Chandana , Xu Shuai , Casas Brooks , Chiu Pearl H.
Published: December 2024

When making risky choices in social contexts, humans typically combine social information with individual preferences about the options at stake. It remains unknown how such decisions are made when these preferences are inaccessible or disrupted, as might be the case for individuals confronting novel options or experiencing cognitive impairment. Thus, we examined participants with lesions in insular or dorsal anterior cingulate cortex, key regions implicated in risky decision-making, as they played a gambling task where choices were made both alone and after observing others’ choices. Participants in both lesion groups showed disrupted use of standard utility-based computations about risky options. For socially situated decisions, these participants showed increased conformity with the choices of others, independent from social utility-based computations. These findings suggest that in social contexts, following others’ choices may be a heuristic for decision-making when utility-based risk processing is disrupted.
scMSI: Accurately inferring the sub-clonal Micro-Satellite status by an integrated deconvolution model on length spectrum
Authors: Liu Yuqian , Chen Yan , Wu Huanwen , Zhang Xuanping , Wang Yuqi , Yi Xin , Liang Zhiyong , Wang Jiayin
Published: December 2024

Microsatellite instability (MSI) is an important genomic biomarker for cancer diagnosis and treatment, and sequencing-based approaches are often applied to identify MSI because of its fastness and efficiency. These approaches, however, may fail to identify MSI on one or more sub-clones for certain cancers with a high degree of heterogeneity, leading to erroneous diagnoses and unsuitable treatments. Besides, the computational cost of identifying sub-clonal MSI can be exponentially increased when multiple sub-clones with different length distributions share MSI status. Herein, this paper proposes “scMSI”, an accurate and efficient estimation of sub-clonal MSI to identify the microsatellite status. scMSI is an integrative Bayesian method to deconvolute the mixed-length distribution of sub-clones by a novel alternating iterative optimization procedure based on a subtle generative model. During the process of deconvolution, the optimized division of each sub-clone is attained by a heuristic algorithm, aligning with clone proportions that adhere optimally to the sample’s clonal structure. To evaluate the performance, 16 patients diagnosed with endometrial cancer, exhibiting positive responses to the treatment despite having negative MSI status based on sequencing-based approaches, were considered. Excitingly, scMSI reported MSI on sub-clones successfully, and the findings matched the conclusions on immunohistochemistry. In addition, testing results on a series of experiments with simulation datasets concerning a variety of impact factors demonstrated the effectiveness and superiority of scMSI in detecting MSI on sub-clones over existing approaches. scMSI provides a new way of detecting MSI for cancers with a high degree of heterogeneity.
Mapping genes for human face shape: Exploration of univariate phenotyping strategies
Authors: Yuan Meng , Goovaerts Seppe , Vanneste Michiel , Matthews Harold , Hoskens Hanne , Richmond Stephen , Klein Ophir D. , Spritz Richard A. , Hallgrimsson Benedikt , Walsh Susan , Shriver Mark D. , Shaffer John R. , Weinberg Seth M. , Peeters Hilde , Claes Peter
Published: December 2024

Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g., inter-landmark distances), unsupervised dimensionality reductions (e.g., principal component analysis (PCA) and auto-encoder (AE) approaches), and assessing resemblance to particular facial gestalts (e.g., syndromic facial archetypes). This study provides a comparative assessment of these strategies in genome-wide association studies (GWASs) of 3D facial shape. Specifically, we investigated inter-landmark distances, PCA and AE-derived latent dimensions, and facial resemblance to random, extreme, and syndromic gestalts within a GWAS of 8,426 individuals of recent European ancestry. Inter-landmark distances exhibit the highest SNP-based heritability as estimated via LD score regression, followed by AE dimensions. Conversely, resemblance scores to extreme and syndromic facial gestalts display the lowest heritability, in line with expectations. Notably, the aggregation of multiple GWASs on facial resemblance to random gestalts reveals the highest number of independent genetic loci. This novel, easy-to-implement phenotyping approach holds significant promise for capturing genetically relevant morphological traits derived from complex biomedical imaging datasets, and its applications extend beyond faces. Nevertheless, these different phenotyping strategies capture different genetic influences on craniofacial shape. Thus, it remains valuable to explore these strategies individually and in combination to gain a more comprehensive understanding of the genetic factors underlying craniofacial shape and related traits.
Different germline variants in the XPA gene are associated with severe, intermediate, or mild neurodegeneration in xeroderma pigmentosum patients
Authors: Sagun Jeffrey P. , Khan Sikandar G. , Imoto Kyoko , Tamura Deborah , Oh Kyu-Seon , DiGiovanna John J. , Kraemer Kenneth H.
Published: December 2024

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by pathogenic variants in seven nucleotide excision repair genes (XPA to XPG) and POLH involved in translesion synthesis. XP patients have a >1000-fold increased risk for sunlight-induced skin cancers. Many Japanese XP-A patients have severe neurological symptoms due to a founder variant in intron 3 of the XPA gene. However, in the United States we found XP-A patients with milder clinical features. We developed a simple scoring scale to assess XP-A patients of varying neurological disease severity. We report 18 XP-A patients examined between 1973 and 2023 under an IRB approved natural history study. Using our scale, we classified our XP-A cohort into severe (n = 8), intermediate (n = 5), and mild (n = 5) disease groups at age 10 years. DNA repair tests demonstrated greatest reduction of DNA repair in cells from severe patients as compared to cells from mild patients. Nucleotide sequencing identified 18 germline pathogenic variants in the 273 amino acid, 6 exon-containing XPA gene. Based on patient clinical features, we associated these XPA variants to severe (n = 8), intermediate (n = 6), and mild (n = 4) clinical phenotypes in the patients. Protein structural analysis showed that nonsense and frameshift premature stop codon pathogenic variants located in exons 3 and 5 correlated with severe disease. Intermediate disease correlated with a splice variant at the last base in exon 4. Mild disease correlated with a frameshift variant in exon 1 with a predicted re-initiation in exon 2; a splice variant that created a new strong donor site in intron 4; and a large genomic deletion spanning exon 6. Our findings revealed correlations between disease severity, DNA repair capacity, and XPA variant type and location. In addition, both XPA alleles contributed to the phenotypic differences in XP-A patients.
The RNA-dependent association of phosphatidylinositol 4,5-bisphosphate with intrinsically disordered proteins contribute to nuclear compartmentalization
Authors: Sztacho Martin , Červenka Jakub , Šalovská Barbora , Antiga Ludovica , Hoboth Peter , Hozák Pavel
Published: December 2024

The RNA content is crucial for the formation of nuclear compartments, such as nuclear speckles and nucleoli. Phosphatidylinositol 4,5-bisphosphate (PIP2) is found in nuclear speckles, nucleoli, and nuclear lipid islets and is involved in RNA polymerase I/II transcription. Intriguingly, the nuclear localization of PIP2 was also shown to be RNA-dependent. We therefore investigated whether PIP2 and RNA cooperate in the establishment of nuclear architecture. In this study, we unveiled the RNA-dependent PIP2-associated (RDPA) nuclear proteome in human cells by mass spectrometry. We found that intrinsically disordered regions (IDRs) with polybasic PIP2-binding K/R motifs are prevalent features of RDPA proteins. Moreover, these IDRs of RDPA proteins exhibit enrichment for phosphorylation, acetylation, and ubiquitination sites. Our results show for the first time that the RDPA protein Bromodomain-containing protein 4 (BRD4) associates with PIP2 in the RNA-dependent manner via electrostatic interactions, and that altered PIP2 levels affect the number of nuclear foci of BRD4 protein. Thus, we propose that PIP2 spatiotemporally orchestrates nuclear processes through association with RNA and RDPA proteins and affects their ability to form foci presumably via phase separation. This suggests the pivotal role of PIP2 in the establishment of a functional nuclear architecture competent for gene expression.
Young men’s everyday life experiences with contraception and unintended pregnancy in Papua New Guinea
Authors: Bell Stephen , Mitchell Elke , Ase Sophie , Aeno Herick , Naketrumb Richard , Ofi Priscilla Selon , Mek Agnes , Pomat William , Habito Marie , Mola Glen , Kennedy Elissa , Kelly-Hanku Angela
Published: December 2024

Unintended adolescent pregnancy is a public health priority in Papua New Guinea (PNG), where national policies specify need for easier access to reliable modern contraceptives. To reduce young people’s experiences of unintended pregnancy in PNG, improved understandings of use of modern and other forms of contraception within young people’s relationships is required to support the development of new sexual and reproductive health (SRH) programs and policies. The aim of this paper is to understand young men’s use of modern and other contraceptives. This qualitative study involved semi-structured interviews with 35 sexually active young men aged 15–24 years, who were sampled purposively from the general population within community-based settings. Data were analysed using inductive thematic analysis techniques. Our analysis of young men’s everyday experiences of using condoms and other contraceptives highlights clear drivers of unintended adolescent pregnancies. Across three settings, these included non-use of any modern method at first sex or during early sexual experiences; inconsistent use of condoms, often only after first pregnancy experiences; difficulties accessing condoms from health service providers, pharmacies and stores; a lack of understanding of other modern contraceptive strategies; inconsistent use of the withdrawal method; and inconsistent and incorrect use of calendar approaches due to misunderstandings about women’s fertile period. Ten young men had never used any form of contraception. These occurred largely because young men’s sexual agency is constrained within sexual and peer relationships, and community, school and health service settings, in ways that inhibit pregnancy prevention. It is important to engage meaningfully with young men to build sexual and reproductive health policies and programs that pay honest, respectful attention to young people’s everyday sexual and social lives. Young men’s everyday stories provide a unique lens through which we can identify mechanisms of change required to address the health and social inequities associated with unintended pregnancy among young men and young women in PNG and beyond.
Landscape of kidney replacement therapy provision in low- and lower-middle income countries: A multinational study from the ISN-GKHA
Authors: Nkunu Victoria , Tungsanga Somkanya , Diongole Hassane M. , Sarki Abdulshahid , Arruebo Silvia , Caskey Fergus J. , Damster Sandrine , Donner Jo-Ann , Jha Vivekanand , Levin Adeera , Nangaku Masaomi , Saad Syed , Ye Feng , Okpechi Ikechi G. , Bello Aminu K. , Johnson David W. , Tonelli Marcello
Published: December 2024

In low- and lower-middle-income countries (LLMICs), delivering equitable kidney care presents substantial challenges, resulting in significant disparities in disease management and treatment outcomes for people with kidney failure. This comprehensive report leveraged data from the International Society of Nephrology-Global Kidney Health Atlas (ISN-GKHA), to provide a detailed update on the landscape of kidney replacement therapy (KRT) in LLMICs. Among the 65 participating LLMICs, reimbursement for KRT (publicly funded by the government and free at the point of delivery) was available in 28%, 15%, and 8% for hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT), respectively. Additionally, while 56% and 28% of LLMICs reported the capacity to provide quality HD and PD, only 41% reported accessibility to chronic dialysis, defined as >50% of the national population being able to access KRT, and a mere 5% LLMICs reported accessibility to KT. Workforce shortages in nephrology further compound these challenges. Kidney registries and comprehensive policies for non-communicable diseases and chronic kidney disease care were limited in LLMICs. A comprehensive and cost-effective approach is crucial to address these challenges. Collaboration at global, regional, country, and individual levels is essential to enhance the quality of kidney care across LLMICs.
Conditional cash transfers and mortality in people hospitalised with psychiatric disorders: A cohort study of the Brazilian Bolsa Família Programme
Authors: Bonfim Camila , Alves Flávia , Fialho Érika , Naslund John A. , Barreto Maurício L. , Patel Vikram , Machado Daiane Borges
Published: December 2024

Background

Psychiatric patients experience lower life expectancy compared to the general population. Conditional cash transfer programmes (CCTPs) have shown promise in reducing mortality rates, but their impact on psychiatric patients has been unclear. This study tests the association between being a Brazilian Bolsa Família Programme (BFP) recipient and the risk of mortality among people previously hospitalised with any psychiatric disorders.

Methods and findings

This cohort study utilised Brazilian administrative datasets, linking social and health system data from the 100 Million Brazilian Cohort, a population-representative study. We followed individuals who applied for BFP following a single hospitalisation with a psychiatric disorder between 2008 and 2015. The outcome was mortality and specific causes, defined according to International Classification of Diseases 10th Revision (ICD-10). Cox proportional hazards models estimated the hazard ratio (HR) for overall mortality and competing risks models estimated the HR for specific causes of death, both associated with being a BFP recipient, adjusted for confounders, and weighted with a propensity score. We included 69,901 psychiatric patients aged between 10 and 120, with the majority being male (60.5%), and 26,556 (37.99%) received BFP following hospitalisation. BFP was associated with reduced overall mortality (HR 0.93, 95% CI 0.87,0.98, p 0.018) and mortality due to natural causes (HR 0.89, 95% CI 0.83, 0.96, p < 0.001). Reduction in suicide (HR 0.90, 95% CI 0.68, 1.21, p = 0.514) was observed, although it was not statistically significant. The BFP’s effects on overall mortality were more pronounced in females and younger individuals. In addition, 4% of deaths could have been prevented if BFP had been present (population attributable risk (PAF) = 4%, 95% CI 0.06, 7.10).

Conclusions

BFP appears to reduce mortality rates among psychiatric patients. While not designed to address elevated mortality risk in this population, this study highlights the potential for poverty alleviation programmes to mitigate mortality rates in one of the highest-risk population subgroups.
Next-generation sequencing guides the treatment of severe community-acquired pneumonia with empiric antimicrobial therapy failure: A propensity-score-matched study
Authors: Zhao Yuhao , Wang Yajuan , Li Yi , Song Chao , Pan Pinhua
Published: December 2024

Background

Next-generation sequencing (NGS) is a promising diagnostic tool for pathogens diagnosis. The aim of this study is to evaluate the application of NGS-based antimicrobial therapy on clinical outcomes in severe community-acquired pneumonia (SCAP) patients with empiric antimicrobial therapy failure.

Methodology

We performed a multi-center, retrospective cohort of SCAP patients with initial empiric therapy failure. Propensity score (PS) matching was used to obtain balance among the baseline variables in NGS group (n = 82) and conventional group (n = 82). We compared the diagnostic performance of NGS with conventional microbial culture. We also compared the impact of NGS-based antimicrobial therapy on the prognosis of patients with empirical antimicrobial therapy failure.

Results

The positive rate of NGS was higher than that of conventional pathogen detection methods (92.6% vs. 74.7%, P = 0.001). Compared to the conventional group, the NGS group has a considerably higher modifications rate of antibiotic treatment (73.2% vs. 54.9%, P = 0.015). The mortality of NGS group was significantly lower than that of conventional group (28.0% vs. 43.9%, P = 0.034). Moreover, the detection of NGS can significantly shorten the ventilation time (P = 0.046), and reduce the antibiotic cost (P = 0.026).

Conclusions

NGS is a valuable tool for microbial identification of SCAP patient with initial empiric therapy failure.
Metagenome-assembled genomes provide insight into the microbial taxonomy and ecology of the Buhera soda pans, Zimbabwe
Authors: Mangoma Ngonidzashe , Zhou Nerve , Ncube Thembekile
Published: December 2024

The use of metagenomics has substantially improved our understanding of the taxonomy, phylogeny and ecology of extreme environment microbiomes. Advances in bioinformatics now permit the reconstruction of almost intact microbial genomes, called metagenome-assembled genomes (MAGs), from metagenomic sequence data, allowing for more precise cell-level taxonomic, phylogenetic and functional profiling of uncultured extremophiles. Here, we report on the recovery and characterisation of metagenome-assembled genomes from the Buhera soda pans located in eastern Zimbabwe. This ecosystem has not been studied despite its unique geochemistry and potential as a habitat for unique microorganisms. Metagenomic DNA from the soda pan was sequenced using the DNA Nanoball Sequencing (DNBSEQR) technique. Sequence analysis, done on the Knowledgebase (KBase) platform, involved quality assessment, read assembly, contig binning, and MAG extraction. The MAGs were subjected to taxonomic placement, phylogenetic profiling and functional annotation in order to establish their possible ecological roles in the soda pan ecosystem. A total of 16 bacterial MAGs of medium to high quality were recovered, all distributed among five phyla dominated by Pseudomonadota and Bacillota. Of the ten MAGs that were taxonomically classified up to genus level, five of them belonged to the halophilic/ haloalkaliphilic genera Alkalibacterium, Vibrio, Thioalkalivibrio, Cecembia and Nitrincola, underscoring the importance of haloalkaliphiles in the Buhera soda pans. Functional profiling revealed the possession of diverse carbohydrate-metabolising pathways by the MAGs, with glycolysis and the pentose phosphate pathways appearing to be key pathways in this ecosystem. Several MAGs possessed pathways that implicated them in some key aspects of the nitrogen and sulphur cycle. Some MAGs harboured both sulphate reduction and respiratory pathways, suggesting a possible mechanism of ATP biosynthesis through sulphate respiration. This study demonstrates the feasibility of the recovery and taxonomic and functional annotation of high quality microbial genomes from extreme environments, making it possible to establish the ecological roles and biotechnological potential of uncultured microorganisms.
Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo
Authors: Tsugawa Yoji , Furukawa Kentaro , Ise Tomoko , Takayama Masahiro , Ota Takeshi , Kuroda Takayuki , Shano Shinya , Hashimoto Takashi , Konishi Haruyo , Ishihara Takeshi , Sato Masaaki , Kamada Haruhiko , Fukao Keita , Shishido Takao , Yoshikawa Mai , Takahashi Tatsuya , Nagata Satoshi
Published: December 2024

The SARS-CoV-2 pandemic alerted the potential for significant harm due to future cross-species transmission of various animal coronaviruses to human. There is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. In this study, we generated CV804, an antibody that binds to the S2 domain of SARS-CoV-2 spike protein, which is highly conserved across the coronavirus family and less susceptible to mutations. CV804 demonstrated broad cross-reactivities not only disease-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and with existing mutant strains of SARS-CoV-2 and but also with 20 representative animal-origin coronaviruses. CV804 exhibits strong antibody-dependent cellular cytotoxicity (ADCC) to SARS-CoV-2 spike protein expressed on cells in vitro, while completely lacks virus-neutralization activity. In animal models, CV804 suppressed disease progression caused by SARS-CoV-2 infection. Structural studies using HDX-MS combined with reactivity analysis with point mutants of recombinant spike proteins revealed that CV804 binds to a unique conformational epitope within the S2 domain of the spike proteins that is highly conserved among various coronaviruses. Overall, obtained data suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein displayed on the surface of infected cells and weakens the viral virulence by supporting the host immune cells’ attack through ADCC activity in vivo. The CV804 epitope information revealed in this study is useful for designing pan-corona antibody therapeutics and universal coronavirus vaccines for preparing potential future pandemics.
Can the assessment of skin injuries and keel bone damage at the slaughterhouse replace on-farm assessments?
Authors: Jung Lisa , Kulig Boris , Louton Helen , Knierim Ute
Published: December 2024

Two major welfare problems in laying hen farming are keel bone damage (KBD) and cannibalism. Their assessment is time-consuming, needs well-trained assessors, and prevalence estimates are often imprecise due to small sample sizes. Here, the bottleneck slaughterhouse comes into focus where large numbers of animals can be inspected. However, this is only an option if the prevalences recorded at the slaughterhouse reasonably agree with on-farm assessments. The aim of this study was to compare the prevalence of KBD and skin injuries in 20 commercial laying hen flocks (i) before depopulation on-farm (ii) after transport and lairage time at arrival at the slaughterhouse, and (iii) at the slaughter line. Bland-Altman plots and equivalence tests were conducted. In addition, the consistency of welfare evaluations of the results according to a traffic light scheme was investigated. Cloacal injuries could not technically be recorded on the slaughter line. With an arbitrary precision of ± 2% for dorsal skin injuries and ± 5% for KBD, the results from farm and slaughter line did not reach equivalence. For dorsal skin injuries, the detected mean prevalence across all flocks examined increased numerically from the farm (15.1%) to the slaughter line (22.8%). In addition, the traffic light evaluations changed between farm and slaughter line in 80% of cases in different directions. Therefore, it cannot be recommended to derive evaluations of on-farm welfare from assessments of skin injuries at the slaughter line. In contrast, the mean detected prevalence of KBD across all flocks decreased consistently (r = 0.794) from the farm (56.0%) to the slaughter line (41.7%). It can be concluded that the assessment of KBD at the slaughter line consistently underestimates KBD prevalences compared to on-farm assessments, but this can be taken into account in the interpretation of the results. Slaughter line assessment of KBD may be a feasible option for monitoring severe welfare problems due to KBD in commercial practice.
Bodily awareness: Religious culture’s associations with interoceptive sensibility
Authors: Van Cappellen Patty , LePage Drummond Tehya M.
Published: December 2024

Religions, as cultural systems, influence how people view and attune to their body. This research explores whether individual differences in various dimensions of religiosity are associated with interoceptive sensibility (IS), i.e., one’s perceived ability to detect and interpret bodily signals. In Study 1, Christians, Muslims, and Hindus (N = 1570) reported their religiosity and completed the Multidimensional Assessment of Interoceptive Awareness, a well-validated measure of IS. Results show that religious identity moderates the relationship between the centrality of religion in one’s life and IS such that the association is positive and medium for Christians, large for Muslims and Hindus. In addition, the medium positive correlation between frequency of religious practice and IS was similar across religious groups. Study 2 (N = 450) extended these results by measuring additional dimensions of religiosity and spirituality as well as investigating religious-related beliefs about the body, both positive (e.g., My body is holy) and negative (e.g., My body is sinful). Associations between religiosity and IS are replicated and found for spirituality as well. Interestingly, mediation analyses reveal that belief in the body as holy partially explains the association between religiosity and IS, but belief in the body as sinful suppresses such association. We discuss how religion, as a cultural factor, may influence beliefs about the body and bodily awareness, with implications for emotion regulation and mental health.