bluuebunny/crossref_metadata_2025 huggingface dataset:
Unanticipated interacting features of human gut-associated lymphoid tissues link microbiota, intestinal immunity and autoimmunity
Authors: Montorsi Lucia , Pitcher Michael J. , Zhao Yuan , Demonti Alicia , Tull Thomas J. , Dionisi Chiara , Dhami Pawan , Ellis Richard J. , Bishop Cynthia , Sanderson Jeremy , Jain Sahil , D’Cruz David , Gibbons Deena , Winkler Thomas H , Bemark Mats , Ciccarelli Francesca D. , Spencer Jo
Published: August 2023

Gut-associated lymphoid tissue (GALT) is organised lymphoid tissue that is chronically activated by the intestinal microbiota. It generates the IgA response that is critical for intestinal homeostasis. By iterative application of multiplexed technologies, we identify enrichment of double-negative 2 (DN2:CD27-IgD-CD21loCD11chi) B cells in GALT, where they comprise the majority of intraepithelial and subepithelial B cells. We show that DN2 B cells in GALT interact with DC in the sub-epithelial dome that expressDNASE1L3and microbicides. Unlike in mice,DNASE1L3in humans does not associate with apoptotic debris, but is located between sampled bacteria and host tissue where it is co-expressed withC1Q, consistent with management of bacterial debris. Thus we demonstrate that DN2 B cells that are otherwise associated with lupus nephritis, and DNASE1L3 and C1q that are lupus autoantigens, are microbiota-associated, interacting components of normal intestinal immunity.
High-speed 3D DNA PAINT and unsupervised clustering for unlocking 3D DNA origami cryptography
Authors: Wisna Gde Bimananda Mahardika , Sukhareva Daria , Zhao Jonathan , Satyabola Deeksha , Matthies Michael , Roy Subhajit , Wang Chao , Šulc Petr , Yan Hao , Hariadi Rizal F.
Published: August 2023

DNA origami information storage is a promising alternative to silicon-based data storage, offering a secure molecular cryptography technique that conceals information within arbitrarily folded DNA origami nanostructures. Routing, sliding, and interlacing staple strands lead to the creation of a large 700-bit key size. The realization of practical DNA data storage requires high information density, robust security, and accurate and rapid information retrieval. To meet these requirements, advanced readout techniques and large encryption key sizes are essential. In this study, we report an enhanced DNA origami cryptography protocol to encrypt information in 2D and 3D DNA origami structures, increasing the number of possible scaffold routings and increasing the encryption key size. We employed all-DNA-based steganography with fast readout through high-speed 2D and 3D DNA-PAINT super-resolution imaging, which enables higher information density. By combining 2D and 3D DNA-PAINT data with unsupervised clustering, we achieved accuracy up to 89% and high ratios of correct-to-wrong readout despite the significant flexibility in the 3D DNA origami structure shown by oxDNA simulation. Furthermore, we propose design criteria that ensure complete information retrieval for the DNA origami cryptography protocol. Our findings demonstrate that DNA-based cryptography is a highly secure and versatile solution for transmitting and storing information, making it an attractive choice for the post-silicon era.
Using metabolic data to uncover the ontogeny of endothermy in an altricial bird
Authors: Engert Elana Rae , Andreasson Fredrik , Nord Andreas , Nilsson Jan-Åke
Published: August 2023

Altricial songbirds transform themselves from naked poikilotherms to fully-feathered endothermic homeotherms over a matter of weeks from hatching to fledging. The timing of development of endothermy has been studied in altricial birds for over half a century. However, the potential determinants, constraints, and flexibility of the onset of endothermy are not yet fully understood. We experimentally investigated whether brood size influences the ontogeny of endothermic heat production in 4-8 day-old nestling blue tits (Cyanistes caeruleus) in southern Sweden. We found that both nestlings’ capacity to produce heat and the proportion of nestlings exhibiting a metabolic response to a cooling challenge (15 °C for 15 min) increased with age. However, we did not find an effect of brood size on the ontogeny of endothermy and this may be explained by the lack of differences in body mass of nestlings in enlarged and reduced broods in our study. The metabolic response in all age groups was brief and not sufficient to sustain a stable body temperature. Our study shows that the development and use of endothermy is present at an early age in nestling blue tits, but further study is needed to disentangle the factors contributing to individual variation in the timing of these developments. This will serve to improve our understanding of a developmental milestone of cold tolerance in birds in the temperate zone that not only face warmer average temperatures, but also increasingly frequent cold snaps and extreme weather.

Summary Statement

This study serves to improve our understanding of the ontogeny of endothermy in altricial birds while examining the potential role of brood size in the timing thereof.
SoundChunk: A free open-source and user oriented R package for acoustic data management, sound detection and extraction
Authors: Villain Avelyne S. , Renaud-Goud Paul
Published: August 2023

In a standard bioacoustic experiment setting, after data collection and before data analysis lies a time-consuming process that consists in extracting and labeling sounds of interest (chunks) from usually long recording files, collected through spreading PAM (Passive Acoustic Monitoring) for instance, and storing them in a structured and exploitable way based on both the meta-data of the initial recordings and the label data.

SoundChunkis a user-oriented package in R that aims at providing tools for any R user so that they can go efficiently and comfortably through this process. Usually, the tasks include detecting, labeling, and extracting sound from audio files. With the recent advance of Machine Learning, especially Convolutional Neural Networks, some of these tasks are integrated in the ML framework; however, the learning phase relies on labeled chunks that need to be created.

Three types of data are involved in the process: (i) WAVE files, whether they come from the initial recordings or are generated by chunk extraction, (ii) meta-data describing the conditions in which the initial WAVE files were recorded, (iii) label track files, whether they are automatically generated or manually input, that contain timed information about audio files.SoundChunkprovides utilities to sanely manipulate each of these three categories and combine them into easy-to-use chunks along with their meta-data.

We expose functionalities that: (i) clean and restructure label tracks that are readable by softwares likeAudacity, (ii) chop long recordings into small fixed-size slices, (iii) detect chunks both interactively (so that robust detection settings can be found on a subset of the recordings) and automatically (so that the detection is applied across all recordings), (iii) dispatch chunks into structured folder(s), according to their meta-data.

Maintainers

The team is open for suggestions and contributions. Contact:soundchunknfeat@proton.me(currently: ASV, PRG).

Users

This document is available as a vignette once the package is loaded an may be used on a set of example data (Villain and Renaud-Goud 2023).
Human Plasma-Like Medium (HPLM) inducesCryptococcus neoformans in vivocell morphologies
Authors: Mozo Eduardo G , Ross Orlando , Yuecel Raif , Dambuza Ivy M. , Mukaremera Liliane
Published: August 2023

The fungal pathogenCryptococcus neoformans (C. neoformans)forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratoryin vitroconditions. Here, we describein vivocell morphologies whenC. neoformansis grown in human plasma-like medium at 37°C-5% CO2. We observed mixed-size populations of cells less than 1 μm up to 16.8 μm cell diameter, increased capsule size, high chitin and DNA content in larger cells. Our findings show serum is not required for HPLM-inducedC. neoformanscellular heterogeneity. Thus, this new method offers an opportunity to investigate factors ofC. neoformansthat mediate pathogenesis or host-pathogen interactions in a physiologically relevant setting.

IMPORTANCE

Description of newin vitroculture condition using the human plasma-like medium that supports the formation of the full range ofin vivocell morphologies ofC. neoformans.
Robust acidic pH and digestive enzyme stability of anti-SarsCov2 IgY antibodies: Implications for treatment of viral transmission thru gastrointestinal, ocular, nasal and skin tissues
Authors: Battula Sanjana , Saranya K , Meher Kranti , Arpitha Reddy R.N , Kadiyala Gopi , Iyer Subramanian , Vangala Subrahmanyam , Chandran Satish , Saxena Uday
Published: August 2023

There are many paths for the transmission of SarsCov2 virus. The main routes are nasal and oral and the droplets carrying the virus can also be transmitted thru ocular and skin tissues. The gastrointestinal (small intestine), nasal, ocular and skin tissues all present an acidic pH milieu and therefore any treatment with antibodies thru these routes has to have the antibodies remain active at acid pH as well as be resistant to typical protease digestion.

To this end we profiled our anti-SarasCov2 receptor binding domain IgY antibodies for retention of activity at acidic and basic pHs and trypsin digestion. We find that the IgY are strongly resistant to denaturation at acid pH as well as not digested by trypsin. Our data strongly support the use of these IgY in treatment of viral transmission thru the GI, nasal, ocular and skin all tissues where the pH is acidic. We also provide an enabling platform to rapidly asses the suitability of any antibody or protein therapeutic for use at acidic pH.
Prickle and Ror modulate Dishevelled-Vangl interaction to regulate non-canonical Wnt signaling during convergent extension
Authors: Seo Hwa-seon , Yu Deli , Popov Ivan , Tao Jiahui , Angermeier Allyson , Sha Bingdong , Axelrod Jeffrey D. , Chang Chenbei , Wang Jianbo
Published: August 2023

Convergent extension (CE) is a fundamental morphogenetic process where oriented cell behaviors lead to polarized extension of diverse tissues. In vertebrates, regulation of CE requires both non-canonical Wnt, its co-receptor Ror, and “core members” of the planar cell polarity (PCP) pathway. PCP was originally identified as a mechanism to coordinate the cellular polarity in the plane of static epithelium, where core proteins Frizzled (Fz)/ Dishevelled (Dvl) and Van Gogh-like (Vangl)/ Prickel (Pk) partition to opposing cell cortex. But how core PCP proteins interact with each other to mediate non-canonical Wnt/ Ror signaling during CE is not clear. We found previously that during CE, Vangl cell-autonomously recruits Dvl to the plasma membrane but simultaneously keeps Dvl inactive. In this study, we show that non-canonical Wnt induces Dvl to transition from Vangl to Fz. PK inhibits the transition, and functionally synergize with Vangl to suppress Dvl during CE. Conversely, Ror is required for the transition, and functionally antagonizes Vangl. Biochemically, Vangl interacts directly with both Ror and Dvl. Ror and Dvl do not bind directly, but can be cofractionated with Vangl. We propose that Pk assists Vangl to function as an unconventional adaptor that brings Dvl and Ror into a complex to serves two functions: 1) simultaneously preventing both Dvl and Ror from ectopically activating non-canonical Wnt signaling; and 2) relaying Dvl to Fz for signaling activation upon non-canonical Wnt induced dimerization of Fz and Ror.
Drug mode of action and resource constraints modulate antimicrobial resistance evolution
Authors: Delaney Oscar , Letten Andrew D. , Engelstädter Jan
Published: August 2023

One of the key characteristics of an antibiotic drug is its mode of action: bacteriostatic or bactericidal. The effect of drug mode of action on the evolution of resistance has been surprisingly underinvestigated to date. We present a theoretical model comparing the efficacy of bacteriostatic and bactericidal drugs, and drugs of intermediate type, at preventing the evolutionary rescue of an initially susceptible bacterial population in a patient. Our results suggest that in resource-abundant environments bacteriostatic drugs are best, as they constrain cell divisions and thus cause fewer resistance mutations to occur. When multiple drugs are employed, using one bacteriostatic and one bactericidal drug is usually optimal, because the cell division rate cannot fall below zero, so there are diminishing returns to bacteriostatic activity from two drugs. We also provide a web-based simulation engine for other researchers to intuitively explore related dynamics without requiring programming expertise.
DNA barcoding revealed a high percentage of mislabeling in commercial fish products: the first empirical survey in South Texas
Authors: Tommasi Rita B. , Lamia Sanjana M. , Van Dysocheata , Estrada Isaiah , Kuchler Zoen L. , Ramsey Dean , Tamang Jyoti , Kaneko Gen , Ehsan Hashimul
Published: August 2023

Seafood mislabeling is a widespread problem that have produced a growing distrust of seafood industry. In this study, we examined the prevalence of mislabeling in fish samples from regional markets in the greater Houston area and close-by coastal communities. A total of 63 fish fillet samples were purchased, labeled, and stored at -20°C in individual packages until DNA extraction. DNA fragments of roughly 700 base pairs encoding cytochrome oxidase I (COI) were PCR-amplified from each DNA sample. With 99.6–100% nucleotide identity in the GenBank and BOLD databases, all samples were correctly identified at the species level. The scientific names identified by DNA barcoding were matched with legally acceptable market names using the US Food and Drug Administration (FDA) Seafood List. Out of the 63 samples examined, 13 samples (20.6%) were mislabeled. Moreover, 24 samples (38.1%) did not use the acceptable market names, indicating that the FDA policy is poorly implemented in seafood industry. The first DNA barcoding survey this area warranted the need of continuous monitoring and the dissemination of the regulation combined with taxonomic knowledge.
Clinical pattern and diagnostic of comorbidity of respiratory tuberculosis and viral pneumonia caused by Herpesvirus Simplex, Human Cytomegalovirus and SARS-CoV-2 in patients with late-stage HIV infection with immunodeficiency
Authors: Mishin V. Yu. , Mishina A.V. , Shashenkov I. V.
Published: August 2023

Aim

To study features of social status, clinical pattern and diagnosis in cases of comorbidity of respiratory tuberculosis and viral pneumonia caused byHerpesvirus Simplexof type 1,Human CytomegalovirusandSARS-CoV-2in patients with late-stage HIV infection with immunodeficiency.

Materials and methods

The prospective study included 25 patients with comorbid condition of respiratory tuberculosis withMycobacterium tuberculosisin excreta, herpesvirus and coronavirus pneumonia, and 21 patients with respiratory tuberculosis as well as cytomegalovirus and coronavirus pneumonia (1a and 2a main groups) and, respectively, 25 and 21 similar patients, but without coronavirus pneumonia (1b and 2b comparison group) in the late stages of HIV infection with immunodeficiency. For the etiological diagnosis of herpesvirus- and cytomegalovirus pneumonia, the PCR test was used for recognition of DNA ofHerpesvirus Simplexof type 1 andHuman Cytomegalovirusin the diagnostic material of respiratory tract and for the etiological diagnosis of coronavirus pneumonia, the PCR for recognition of RNA was used to revealSARS–CoV-2. Statistical analysis of the data was performed by the use of the Microsoft Office Excel 2019 software for calculation of group mean, standard error of mean and confidence interval.

Results

The comorbidity of respiratory tuberculosis, herpes-, cytomegalo- and coronavirus pneumonia in patients with late-stage HIV infection in the phase of progression and in the absence of ART was characterized by severe immunodeficiency and generalization of tuberculosis with multiple extrapulmonary lesions. The results displayed similarity of clinical manifestations and visualization of changes in CT-picture in cases of comorbidity the diseases which hampers their recognition due to simultaneous combination of several pathologies with similar clinical manifestations that requires a complex etiological diagnosis of the specific diseases to prescribe a timely comprehensive treatment and reduce lethality in this severe contingent of patients.

Conclusion

Patients with respiratory tuberculosis and HIV infection registered in the office of tuberculosis care for HIV-infected individuals in the antituberculosis dispensary represent a group of high risk from COVID-19 infection and CVP disease, and, in cases of combination with severe immunodeficiency, HVP and CMVP, the patients should be regularly subjected to preventive studies for timely detection of COVID-19 for the purpose of their emergency isolation and treatment.
Sexual health in women with Parkinson’s disease: Motor, non-motor, and social impacts
Authors: Nobrega Kátia Cirilo Costa , da Silva Nascimento Isaíra Almeida Pereira , Souza Bruno Rafael Antunes , Gonçalves Raissa Amorim , Martins Thalyta Silva , Santos Geovanna Ferreira , de Almeida da Silva Bruno Eron , Helene André Frazão , Roque Antonio Carlos , Savica Rodolfo , Piemonte Maria Elisa Pimentel
Published: August 2023

Background

Sexual dysfunction (SD) is a common non-motor symptom (NMS) in people with Parkinson’s disease (PwPD). Sexual health (SH) depends on several biological, mental, and social factors that PD may affect. Despite its prevalence and relevance for quality of life, SD in women with Parkinson’s disease (WwPD) is poorly understood, and research in this area is scarce.

Objectives

To investigate the impact of motor, non-motor, and social aspects on the SH of WwPD.

Methods

We conducted a cross-sectional study of 100 women (mean age 54.45±8.31, mean H&Y stage 1.70±0.71). The following data were collected for each person (used tests/scales indicated within parentheses and defined in Glossary): (1) demographic information and global cognitive capacity (T-MoCA); (2) non-motor aspects of daily life experiences (MDS-UPDRS, part I); (3) motor aspects of daily life experiences (MDS-UPDRS, part II); (4) fatigue (FSS); (5) self-esteem (RSES); (6) sleep disorder (PDSS); (7) couple relationship quality (CRQ) (DAS); (8) depressive signals (BDI); (8) short-term sexual health (FSFI); and (9) long-term sexual health (SQ-F).

Results

Our results suggest that depressive symptoms, preserved cognitive status, and CRQ are predictive factors in the sexual health of WwPD. Age, disease onset, duration, postmenopausal, Levodopa dosage, motor disability, and fatigue were not correlated with SH.

Conclusion

Our findings emphasize the need to assess the sexual functioning of WwPD to investigate which motor, non-motor, and social aspects may be involved in SD so that measures can be implemented in clinical practice.
Dynamic coordination of the lever-arm swing of human myosin II in thick filaments on actin
Authors: Fukunaga Hiroki , Washio Takumi , Fujita Keisuke , Ohmachi Masashi , Takagi Hiroaki , Ikezaki Keigo , Yanagida Toshio , Iwaki Mitsuhiro
Published: August 2023

Muscle myosins work in motor ensembles and must adapt their power stroke in response to mechanical actions by surrounding motors. Understanding the coordination of power strokes is essential for bridging microscopic molecular functions and macroscopic muscle contractions, but the details of this phenomenon remain elusive. Here we used high-speed atomic force microscopy to visualize the individual dynamics (lever-arm swing) of the myosin head bound to actin in DNA origami–based synthetic thick filaments. We observed spatially local lever-arm coordination, and our three-dimensional numerical model explained how mechanical communication between myosins achieved coordination. In a sarcomere model, the local coordination was spatially periodic and propagated toward the contraction direction. We confirmed that a structural mismatch between myosin head spacing (42.8 nm) and the actin helical pitch (37 nm) caused the coordination while improving contraction speed and energy efficiency. Our findings reveal a key physical basis of efficient muscle contraction.
Dance or disappear: Strategic sexual signalling in female Peninsular rock agama
Authors: Sridharan Aravind , Lawrence Swapna , Isvaran Kavita
Published: August 2023

Sexual signalling has largely been studied in the context of indirect competition among males through displays and mate choice by females. Historically, sexual signalling in females was expected to be of limited consequence. However, there is growing evidence of sexual signalling in females and its value in the context of sexual selection. Here, we test how females strategize the use of sexual signals in a socially polygynous lizard,Psammophilus dorsalis. We evaluated key hypotheses for how females should modulate their signalling, including male quality and mate availability. We simulate male quality using artificial male models to individually tagged, and intensely monitored wild female lizards, measuring their strategic investment in sexual signalling. We found that females invest more in signalling towards high quality males and increased their investment towards the later part of the only breeding season. Contrary to what is typically expected in a polygynous mating system, females not only invest in costly and elaborate sexual signals, they also modulate their usage to maximise their benefits and minimise their costs. Even in polygynous mating systems, dispersed distribution of individuals can result in females experiencing limitation in mate availability, resulting in costly sexual signalling.
Evidence of target-mediated miRNA degradation inDrosophilaovarian cell culture
Authors: Akulenko Natalia , Mikhaleva Elena , Marfina Sofya , Kornyakov Dmitry , Bobrov Vlad , Arapidi Georgij , Shender Victoria , Ryazansky Sergei
Published: August 2023

Target-mediated miRNA degradation (TDMD) is a recently discovered process of post-transcriptional regulation of miRNA stability in animals. TDMD is induced by the formation of the non-canonical duplex of Ago-bound miRNAs with the specialized RNA target, and, as suggested for human cell culture, this complex is recognized by the ZSWIM8 receptor protein of the Cullin-RING-ligase complex CRL3. CRL3 ubiquitinates Ago, resulting in proteolysis of Ago and degradation of the released miRNAs. To date, the molecular mechanism of the TDMD process was not studied in other animal species. Here we investigated protein Dora, theDrosophilaortholog of ZSWIM8, in the culture ofDrosophilaovarian somatic cells (OSC). We show that Dora in OSCs localizes in protein granules that are not related to P-and GW-bodies. The knock-out ofDoraup-regulates multiple miRNAs, including miR-7-5p. Also, we show that Dora associates with proteins of the CRL3 complex, and the depletion of its main component Cul3 up-regulates miR-7-5p. We concluded that the mechanism of TDMD is conserved in humans andDrosophila. The knock-out ofDoraalso down-regulates the putative protein-coding targets of miRNAs. One of them isTomfrom the Brd-C gene family, which is known to repress the Notch signaling pathway. Indeed, in cells lacking Dora, we have observed the down-regulation ofcut, the marker of the activated Notch pathway. This data indicates that TDMD in OSCs may contribute to modulation of the Notch pathway.
Influence of pseudo-green water on growth, colouration, and survival in European lobster (Homarus gammarus) larvae
Authors: Bell Matt E , Grady Julie O , Domech Paula C , Frontaura Erik R , Hinchcliffe James , Davies Simon J , McCusker Stephen , Wan Alex H L
Published: August 2023

With the depletion of European lobster (Homarus gammarus) wild stocks from historic overexploitation, the attention has turned towards restocking, stock enhancement programs and farming potential. The early life larval stages of the European lobster present a major barrier to hatchery production efforts due to low survival rates. Green water techniques are rapidly growing due to their ability to improve nutrition quality. This study explores the potential benefits of using pseudo-green water. This is determined by adding microalgae to the rearing environment of larvae by analysing the effects on growth and survival. The commonly used algal species:Tetraselmis suecica(TS),Dunaliella salina(DS), andNannochloropsissp. (N) were added as monoculture or mixture treatments to a controlled European lobster larvae-rearing environment over thirteen days. The trial consisted of seven permutations of algal treatments (TS, DS, N, TS+DS, TS+N, DS+N, and TS+DS+N) and one control group, with clear water conditions using length measurements, survival rates and colouration to determine treatment impacts at the end of the trial. Results indicate that mixtures of algal species outperformed monocultures and clear water regarding growth performance.Nannochloropsissp. is of significant benefit to growth performance. Algal mixes containingNannochloropsissp. resulted in significantly better growth thanD.salinamonoculture treatment. There were no significant differences in survival rates between treatment groups.
Microbial cell factory optimisation using genome-wide host-pathway interaction screens
Authors: Cachera Paul , Kurt Nikolaj Can , Røpke Andreas , Strucko Tomas , Mortensen Uffe H. , Jensen Michael K.
Published: August 2023

The ubiquity of genetic interactions in living cells challenges the concept of parts orthogonality, which is a cornerstone of synthetic biology. Parts, such as heterologously expressed genes, draw from shared pools of limited cellular resources and interactions between parts themselves and their host are inevitable. Instead of trying to eliminate or disregard these interactions, we propose to leverage them to promote desirable phenotypes. We recently described CRI-SPA, a method for high-throughput genome-wide gene delivery and screening of host:pathway interactions inSaccharomyces cerevisiae. In this study, we combine this method with biosensor-based high-throughput screening and high-density colony image analysis to identify lead engineering targets for optimisingcis-cis-muconic acid (CCM) production in yeast cell factories. Using the biosensor screen, we phenotype >9,700 genotypes for their interaction with the heterologously expressed CCM biosynthesis pathway, including both gene knock-out and overexpression, and identify novel metabolic targets belonging to sulphur assimilation and methionine synthesis, as well as cellular redox homeostasis, positively impacting CCM biosynthesis by up to 280%. Our genome-wide exploration of host pathway interaction opens novel strategies for the metabolic engineering of yeast cell factories.
Inhibiting NINJ1-dependent plasma membrane rupture protects against inflammasomeinduced blood coagulation and inflammation
Authors: Cui Jian , Li Hua , Ye Dien , Zhang Guoying , Zhang Yan , Yang Ling , Sim Martha M.S. , Wood Jeremy P. , Wei Yinan , Li Zhenyu , Wu Congqing
Published: August 2023

Systemic blood coagulation accompanies inflammation during severe infection like sepsis and COVID. We’ve previously established a link between pyroptosis, a vital defense mechanism against infection, and coagulopathy. During pyroptosis, the formation of gasdermin-D (GSDMD) pores on the plasma membrane leads to the release of tissue factor (TF)-positive microvesicles (MVs) that are procoagulant. Mice lacking GSDMD release fewer TF MVs. However, the specific mechanisms leading from activation of GSDMD to MV release remain unclear. Plasma membrane rupture (PMR) in pyroptosis was recently reported to be actively mediated by the transmembrane protein Ninjurin-1 (NINJ1). Here we show that NINJ1 promotes procoagulant MV release during pyroptosis. Haploinsuffciency or glycine inhibition of NINJ1 limited the release of procoagulant MVs and inflammatory cytokines and partially protected against blood coagulation and lethality triggered by bacterial flagellin. Our findings suggest a crucial role for NINJ1-dependent PMR in inflammasome-induced blood coagulation and inflammation.
Generation of isogenic models of Angelman syndrome and Prader-Willi syndrome in CRISPR/Cas9-engineered human embryonic stem cells
Authors: Gilmore Rachel B. , Gorka Dea , Stoddard Christopher E. , Cotney Justin L. , Chamberlain Stormy J
Published: August 2023

Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS), two distinct neurodevelopmental disorders, result from loss of expression from imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either the maternal or paternal allele, respectively. Each occurs at an approximate incidence of 1/15,000 to 1/30,000 live births and has a range of debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools to understand human-relevant gene regulation at this locus and have contributed to the development of therapeutic approaches for AS. Nonetheless, gaps remain in our understanding of how these deletions contribute to dysregulation and phenotypes of AS and PWS. Variability across cell lines due to donor differences, reprogramming methods, and genetic background make it challenging to fill these gaps in knowledge without substantially increasing the number of cell lines used in the analyses. Isogenic cell lines that differ only by the genetic mutation causing the disease can ease this burden without requiring such a large number of cell lines. Here, we describe the development of isogenic human embryonic stem cell (hESC) lines modeling the most common genetic subtypes of AS and PWS. These lines allow for a facile interrogation of allele-specific gene regulation at the chromosome 15q11-q13 locus. Additionally, these lines are an important resource to identify and test targeted therapeutic approaches for patients with AS and PWS.
Unravelling human hematopoietic progenitor cell diversity through association with intrinsic regulatory factors
Authors: Favaro Patricia , Glass David R. , Borges Luciene , Baskar Reema , Reynolds Warren , Ho Daniel , Bruce Trevor , Tebaykin Dmitry , Scanlon Vanessa M. , Shestopalov Ilya , Bendall Sean C.
Published: August 2023

Hematopoietic stem and progenitor cell (HSPC) transplantation is an essential therapy for hematological conditions, but finer definitions of human HSPC subsets with associated function could enable better tuning of grafts and more routine, lower-risk application. To deeply phenotype HSPCs, following a screen of 328 antigens, we quantified 41 surface proteins and functional regulators on millions of CD34+ and CD34- cells, spanning four primary human hematopoietic tissues: bone marrow, mobilized peripheral blood, cord blood, and fetal liver. We propose more granular definitions of HSPC subsets and provide new, detailed differentiation trajectories of erythroid and myeloid lineages. These aspects of our revised human hematopoietic model were validated with corresponding epigenetic analysis andin vitroclonal differentiation assays. Overall, we demonstrate the utility of using molecular regulators as surrogates for cellular identity and functional potential, providing a framework for description, prospective isolation, and cross-tissue comparison of HSPCs in humans.
HCR spectral imaging: 10-plex, quantitative, high-resolution RNA and protein imaging in highly autofluorescent samples
Authors: Schulte Samuel J. , Fornace Mark E. , Hall John K. , Pierce Niles A.
Published: August 2023

Signal amplification based on the mechanism of hybridization chain reaction (HCR) provides a unified framework for multiplex, quantitative, high-resolution imaging of RNA and protein targets in highly autofluorescent samples. With conventional bandpass imaging, multiplexing is typically limited to four or five targets due to the difficulty in separating signals generated by fluorophores with overlapping spectra. Spectral imaging has offered the conceptual promise of higher levels of multiplexing, but it has been challenging to realize this potential in highly autofluorescent samples including whole-mount vertebrate embryos. Here, we demonstrate robust HCR spectral imaging with linear unmixing, enabling simultaneous imaging of 10 RNA and/or protein targets in whole-mount zebrafish embryos and mouse brain sections. Further, we demonstrate that the amplified and unmixed signal in each of 10 channels is quantitative, enabling accurate and precise relative quantitation of RNA and/or protein targets with subcellular resolution, and RNA absolute quantitation with single-molecule resolution, in the anatomical context of highly autofluorescent samples.

Spectral imaging with signal amplification based on the mechanism of hybridization chain reaction enables robust 10-plex, quantitative, high-resolution imaging of RNA and protein targets in whole-mount vertebrate embryos and brain sections.
Respiratory syncytial virus-associated hospitalisation in adults with comorbidities in two European countries
Authors: Osei-Yeboah Richard , Johannesen Caroline , Egeskov-Cavling Amanda Marie , Chen Junru , Lehtonen Toni , Fornes Arantxa Urchueguía , Paget John , Fischer Thea K. , Wang Xin , Nair Harish , Campbell Harry
Published: August 2023

Background

Individuals with comorbidities are at increased risk of severe RSV infection. We estimated RSV-associated respiratory tract infection (RTI) hospitalisation among adults aged 45 years and older with comorbidities in Denmark and Scotland.

Methods

By analysing national hospital and virological data, we estimated annual average number and rate of RSV-associated hospitalisations by seven selected comorbidities and age during 2010-2018. We estimated rate ratios (RRs) of RSV-associated hospitalisation and 95% uncertainty ranges in comorbid adults versus the overall populations.

Results

In Danish adults aged 45y+, RSV-RTI hospitalisation rates ranged from 3.1 per 1000 individuals with asthma, to 19.4 per 1000 individuals per year with chronic kidney disease (CKD). In Scotland, the rate ranged from 2.4 per 1000 individuals per year with chronic liver disease (CLD), to 9.0 per 1000 individuals per year with chronic obstructive pulmonary disease (COPD). In both countries, we found over 2-4-fold increased risk of RSV hospitalisation in adults with COPD, ischemic heart disease (IHD), stroke and diabetes, and 1.5-3-fold increased risk for adults with asthma and 3-7-fold for those with CKD. RSV hospitalisation rates among adults aged 45-64y with COPD, asthma, IHD or CKD were higher compared with the overall population aged 65-74y.

Conclusion

Findings of this study provide important evidence for identifying risk groups and assisting health authorities in RSV vaccination policy making.
The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer
Authors: Al Assaad Majd , Gundem Gunes , Liechty Benjamin , Sboner Andrea , Medina Juan , Papaemmanuil Elli , Sternberg Cora N. , Marks Asher , Souweidane Mark M. , Greenfield Jeffrey P. , Tran Ivy , Snuderl Matija , Elemento Olivier , Imielinski Marcin , Pisapia David J. , Mosquera Juan Miguel
Published: August 2023

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative forBRAFrearrangement but harboring aBRAFp.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication inFGFR1and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.
Foreign language effect in negotiations: negotiation language and framing effect on contract terms and subjective outcomes
Authors: Lee Jung Hyun , Elfenbein Hillary Anger , Bottom William P.
Published: August 2023

Purpose

This study aims to test negotiation outcomes when bilinguals negotiate in a foreign rather than their native language. Decision research on the foreign language effect indicates that bilingual individuals may be less susceptible to framing bias when using a foreign language because they make less emotional and biased choices. With increasing international business activity, there is a pressing need to examine the effect of language on bilingual negotiators.

Design/methodology/approach

The authors tested the hypotheses using a two (task frame: gain vs loss) × 2 (language: foreign vs native) factorial design recruiting 246 Korean–English bilinguals. A negotiation simulation with three issues was used, and participants exchanged offers with a preprogrammed computer they believed to be a real counterpart.

Findings

There was no significant interaction effect between framing and language on the offers made, but the framing effect was mitigated and nonsignificant for negotiators who used their foreign language. The interaction between framing and language conditions significantly affected negotiators’ positive emotions and satisfaction with the negotiation.

Originality/value

The uniqueness of this paper is related to its effort to investigate the effect of negotiation language on a negotiator’s decision-making. Considering globalization and the increasing prevalence of international negotiations, this paper has implications for researchers and practitioners.
Impact of entrepreneurial education, trait competitiveness and psychological capital on entrepreneurial behavior of university students in GCC
Authors: Abubakar Ahmed , Mourgan Fatma Hassan Abdelbasset , Al Kharusi Buthaina , Elfitori Chadilia Mohammed
Published: August 2023

Purpose

This research is in response to the growing need for economic diversification in the Gulf Cooperation Council (GCC) countries as they seek to manage the impacts of volatile oil revenues. To this end, governments in the region are encouraging their citizens to undertake entrepreneurial activities. The purpose of this study is to examine the effects of entrepreneurial education (EE), trait competitiveness (TC) and psychological capital (PC) on the entrepreneurial behavior (EB) of university students.

Design/methodology/approach

As a quantitative study, primary data were collected through a survey administered to the team of young university students in Oman. Using stratified sampling techniques, 858 questionnaires were retrieved and used for the analysis out of the 1,176 sample. The analysis of the data was done using structural equation modeling.

Findings

The results have established a positive influence of EE, TC and PC on the EB of university students in the GCC region. This study also found that PC acts as a bridge between EE, TC and EB.

Originality/value

This paper provides further literature evidence on the contribution of other variables like TC and PC to EB, particularly in the GCC context, by providing a model of the influence mechanism on EB. This research reveals a very unique influence of PC on the relationship between TC and EB. The findings confirm that there is no direct relationship between TC and EB. However, the relationship was established with the introduction of PC.
Data‐driven identification of major axes of functional variation in bacteria
Authors: Lajoie Geneviève , Kembel Steven W.
Published: August 2023

The discovery of major axes of correlated functional variation among species and habitats has revealed the fundamental trade‐offs structuring both functional and taxonomic diversity in eukaryotes such as plants. Whether such functional axes exist in the bacterial realm and whether they could explain bacterial taxonomic turnover among ecosystems remains unknown. Here, we use a data‐driven approach to leverage global genomic and metagenomic datasets to reveal the existence of major axes of functional variation explaining both evolutionary differentiation within Bacteria and their ecological sorting across diverse habitats. We show that metagenomic variation among bacterial communities from various ecosystems is structured along a few axes of correlated functional pathways. Similar clusters of traits explained phylogenetic trait variation among >16,000 bacterial genomes, suggesting that functional turnover among bacterial communities from distinct habitats does not only result from the differential filtering of similar functions among communities, but also from phylogenetic correlations among these functions. Concordantly, functional pathways associated with trait clusters that were most important for defining functional turnover among bacterial communities were also those that had the highest phylogenetic signal in the bacterial genomic phylogeny. This study overall underlines the important role of evolutionary history in shaping contemporary distributions of bacteria across ecosystems.
Mutations of voltage‐gated sodium channel contribute to pyrethroid resistance in Panonychus citri
Authors: Pan Deng , Luo Qiu‐Juan , O´Reilly Andrias O. , Yuan Guo‐Rui , Wang Jin‐Jun , Dou Wei
Published: August 2023

Insecticide resistance in Panonychus citri is a major obstacle to mite control in citrus orchards. Pyrethroid insecticides are continually used to control mites in China, although resistance to pyrethroids has evolved in some populations. Here, the resistance to the pyrethroid fenpropathrin was investigated and 7 out of 8 field‐collected populations of P. citri exhibited a high level of resistance, ranging from 171‐fold to 15 391‐fold higher than the susceptible (SS) comparison strain. Three voltage‐gated sodium channel (VGSC) mutations were identified in the tested populations: L1031V, F1747L, and F1751I. Amplicon sequencing was used to evaluate the frequency of these mutations in the 19 field populations. L1031V and F1751I were present in all populations at frequencies of 11.6%–82.1% and 0.5%–31.8%, respectively, whereas the F1747L mutation was only present in 12 populations from Chongqing, Sichuan, Guangxi, and Yunnan provinces. Introduction of these mutations singly or in combination into transgenic flies significantly increased their resistance to fenpropathrin and these flies also exhibited reduced mortality after exposure to the pyrethroids permethrin and β‐cypermethrin. Panonychus citri VGSC homology modeling and ligand docking indicate that F1747 and F1751 form direct binding contacts with pyrethroids, which are lost with mutation, whereas L1031 mutation may diminish pyrethroid effects through an allosteric mechanism. Overall, the results provide molecular markers for monitoring pest resistance to pyrethroids and offer new insights into the basis of pyrethroid actions on sodium channels.
The consequences of neglecting reservoir storage in national‐scale hydrologic models: An appraisal of key streamflow statistics
Authors: Hodgkins Glenn A. , Over Thomas M. , Dudley Robert W. , Russell Amy M. , LaFontaine Jacob H.
Published: August 2023

A better understanding of modeled streamflow errors related to basin reservoir storage is needed for large regions, which normally have many ungaged basins with reservoirs. We quantified the difference between modeled and observed streamflows for one process‐based and three statistical‐transfer hydrologic models, none of which explicitly accounted for reservoir storage. Streamflow statistics representing low to high flows, seasonality, annual variability, and daily autocorrelation were examined at 1082 study basins across the conterminous USA. All models increasingly overpredict (or decreasingly underpredict) observed annual maximum flows with increasing storage. Correlations between absolute values of errors for low‐flow statistics and storage are often larger in magnitude than those for signed errors—additional storage is associated with increases in model errors in both directions even when its overall effect in one direction is weak. The rate of increase in absolute values of model errors was nonlinear for most statistics. For low flows, model errors had a change point to larger errors at 48 days of reservoir storage (relative to long‐term mean daily flow); mean and high flows had change points at 147 to 176 days. We present predicted‐to‐observed errors for nine streamflow statistics over a large range of reservoir storage to help modelers and users of modeled streamflow understand the amount of storage for which explicit reservoir modeling is needed.
Endogenous opioid system modulates conditioned cocaine reward in a sex‐dependent manner
Authors: Matsumura Kanako , Nicot Amélia , Choi In Bae , Asokan Meera , Le Nathan N. , Natividad Luis A. , Dobbs Lauren K.
Published: August 2023

Cocaine predictive cues and contexts exert powerful control over behaviour and can incite cocaine seeking and taking. This type of conditioned behaviour is encoded within striatal circuits, and these circuits and behaviours are, in part, regulated by opioid peptides and receptors expressed in striatal medium spiny neurons. We previously showed that augmenting levels of the opioid peptide enkephalin in the striatum facilitates acquisition of cocaine conditioned place preference (CPP), while opioid receptor antagonists attenuate expression of cocaine CPP. However, whether striatal enkephalin is necessary for acquisition of cocaine CPP and maintenance during extinction remains unknown. To address this, we generated mice with a targeted deletion of enkephalin from dopamine D2‐receptor expressing medium spiny neurons and tested them in a cocaine CPP paradigm. Low striatal enkephalin levels did not attenuate acquisition of CPP. However, expression of preference, assessed after acute administration of the opioid receptor antagonist naloxone, was blocked in females, regardless of genotype. When saline was paired with the cocaine context during extinction sessions, females, regardless of genotype, extinguished preference faster than males, and this was prevented by naloxone when paired with the cocaine context. We conclude that while striatal enkephalin is not necessary for acquisition, expression, or extinction of cocaine CPP, expression and extinction of cocaine preference in females is mediated by an opioid peptide other than striatal enkephalin. The unique sensitivity of females to opioid antagonists suggests sex should be a consideration when using these compounds in the treatment of cocaine use disorder.
Psoriasiform graft‐versus‐host disease responded to secukinumab: A case report
Authors: Gu Ying , Sun Jing , Zhang Jianzhong
Published: August 2023

We describe a 9‐year‐old boy who developed generalised erythematous lesions 12 months after haematopoietic stem cell transplant (HSCT). Histopathology showed both features of psoriasis and graft‐versus‐host disease (GVHD). The lesions responded well to secukinumab, suggesting that IL‐17A monoclonal antibody might be a treatment option for GVHD.