bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic determinants of micronucleus formation in vivo
Authors: Adams D. J. , Barlas B. , McIntyre R. E. , Salguero I. , van der Weyden L. , Barros A. , Vicente J. R. , Karimpour N. , Haider A. , Ranzani M. , Turner G. , Thompson N. A. , Harle V. , Olvera-León R. , Robles-Espinoza C. D. , Speak A. O. , Geisler N. , Weninger W. J. , Geyer S. H. , Hewinson J. , Karp N. A. ,   The Sanger Mouse Genetics Project, Tudor Catherine L. , Green Angela L. , Mazzeo Cecilia Icoresi , Siragher Emma , Lillistone Charlotte , Gleeson Diane , Sethi Debarati , Bayzetinova Tanya , Burvill Jonathan , Habib Bishoy , Weavers Lauren , Maswood Ryea , Miklejewska Evelina , Woods Michael , Grau Evelyn , Newman Stuart , Sinclair Caroline , Brown Ellen , Doe Brendan , Galli Antonella , Ramirez-Solis Ramiro , Ryder Edward , Steel Karen , Bradley Allan , Skarnes William C. , Adams David J. , Lafont David , Vancollie Valerie E. , McLaren Robbie S. B. , Hughes-Hallett Lena , Rowley Christine , Sanderson Emma , Tuck Elizabeth , Dabrowska Monika , Griffiths Mark , Gannon David , Cockle Nicola , Kirton Andrea , Bottomley Joanna , Ingle Catherine , Lelliott Chris , White Jacqueline K. , Fu B. , Yang F. , Kozik Z. , Choudhary J. , Yu L. , van Ruiten M. S. , Rowland B. D. , Lelliott C. J. , del Castillo Velasco-Herrera M. , Verstraten R. , Bruckner L. , Henssen A. G. , Rooimans M. A. , de Lange J. , Mohun T. J. , Arends M. J. , Kentistou K. A. , Coelho P. A. , Zhao Y. , Zecchini H. , Perry J. R. B. , Jackson S. P. , Balmus G.
Published: February 2024

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR–Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.
Influence of pump laser fluence on ultrafast myoglobin structural dynamics
Authors: Barends Thomas R. M. , Gorel Alexander , Bhattacharyya Swarnendu , Schirò Giorgio , Bacellar Camila , Cirelli Claudio , Colletier Jacques-Philippe , Foucar Lutz , Grünbein Marie Luise , Hartmann Elisabeth , Hilpert Mario , Holton James M. , Johnson Philip J. M. , Kloos Marco , Knopp Gregor , Marekha Bogdan , Nass Karol , Nass Kovacs Gabriela , Ozerov Dmitry , Stricker Miriam , Weik Martin , Doak R. Bruce , Shoeman Robert L. , Milne Christopher J. , Huix-Rotllant Miquel , Cammarata Marco , Schlichting Ilme
Published: February 2024

High-intensity femtosecond pulses from an X-ray free-electron laser enable pump–probe experiments for the investigation of electronic and nuclear changes during light-induced reactions. On timescales ranging from femtoseconds to milliseconds and for a variety of biological systems, time-resolved serial femtosecond crystallography (TR-SFX) has provided detailed structural data for light-induced isomerization, breakage or formation of chemical bonds and electron transfer1,2. However, all ultrafast TR-SFX studies to date have employed such high pump laser energies that nominally several photons were absorbed per chromophore3–17. As multiphoton absorption may force the protein response into non-physiological pathways, it is of great concern18,19whether this experimental approach20allows valid conclusions to be drawn vis-à-vis biologically relevant single-photon-induced reactions18,19. Here we describe ultrafast pump–probe SFX experiments on the photodissociation of carboxymyoglobin, showing that different pump laser fluences yield markedly different results. In particular, the dynamics of structural changes and observed indicators of the mechanistically important coherent oscillations of the Fe–CO bond distance (predicted by recent quantum wavepacket dynamics21) are seen to depend strongly on pump laser energy, in line with quantum chemical analysis. Our results confirm both the feasibility and necessity of performing ultrafast TR-SFX pump–probe experiments in the linear photoexcitation regime. We consider this to be a starting point for reassessing both the design and the interpretation of ultrafast TR-SFX pump–probe experiments20such that mechanistically relevant insight emerges.
A new family of bacterial ribosome hibernation factors
Authors: Helena-Bueno Karla , Rybak Mariia Yu. , Ekemezie Chinenye L. , Sullivan Rudi , Brown Charlotte R. , Dingwall Charlotte , Baslé Arnaud , Schneider Claudia , Connolly James P. R. , Blaza James N. , Csörgő Bálint , Moynihan Patrick J. , Gagnon Matthieu G. , Hill Chris H. , Melnikov Sergey V.
Published: February 2024

To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage1,2. In bacteria, two families of hibernation factors have been described, but the low conservation of these proteins and the huge diversity of species, habitats and environmental stressors have confounded their discovery3–6. Here, by combining cryogenic electron microscopy, genetics and biochemistry, we identify Balon, a new hibernation factor in the cold-adapted bacterium Psychrobacter urativorans. We show that Balon is a distant homologue of the archaeo-eukaryotic translation factor aeRF1 and is found in 20% of representative bacteria. During cold shock or stationary phase, Balon occupies the ribosomal A site in both vacant and actively translating ribosomes in complex with EF-Tu, highlighting an unexpected role for EF-Tu in the cellular stress response. Unlike typical A-site substrates, Balon binds to ribosomes in an mRNA-independent manner, initiating a new mode of ribosome hibernation that can commence while ribosomes are still engaged in protein synthesis. Our work suggests that Balon–EF-Tu-regulated ribosome hibernation is a ubiquitous bacterial stress-response mechanism, and we demonstrate that putative Balon homologues in Mycobacteria bind to ribosomes in a similar fashion. This finding calls for a revision of the current model of ribosome hibernation inferred from common model organisms and holds numerous implications for how we understand and study ribosome hibernation.
A model of human neural networks reveals NPTX2 pathology in ALS and FTLD
Authors: Hruska-Plochan Marian , Wiersma Vera I. , Betz Katharina M. , Mallona Izaskun , Ronchi Silvia , Maniecka Zuzanna , Hock Eva-Maria , Tantardini Elena , Laferriere Florent , Sahadevan Sonu , Hoop Vanessa , Delvendahl Igor , Pérez-Berlanga Manuela , Gatta Beatrice , Panatta Martina , van der Bourg Alexander , Bohaciakova Dasa , Sharma Puneet , De Vos Laura , Frontzek Karl , Aguzzi Adriano , Lashley Tammaryn , Robinson Mark D. , Karayannis Theofanis , Mueller Martin , Hierlemann Andreas , Polymenidou Magdalini
Published: February 2024

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1, which involve human-specific mechanisms2–5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors6. Single-cell transcriptomics and comparison to independent neural stem cells7 showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids8. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3′ untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity.
Autonomous transposons tune their sequences to ensure somatic suppression
Authors: Ilık İbrahim Avşar , Glažar Petar , Tse Kevin , Brändl Björn , Meierhofer David , Müller Franz-Josef , Smith Zachary D. , Aktaş Tuğçe
Published: February 2024

Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-messenger RNA synthesis, intronic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product because they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns1, and also functional2 or non-functional chimeric transcripts3. The rarity of these events implies the existence of a resilient splicing code that is able to suppress TE exonization without compromising host pre-mRNA processing. Here we show that SAFB proteins protect genome integrity by preventing retrotransposition of L1 elements while maintaining splicing integrity, via prevention of the exonization of previously integrated TEs. This unique dual role is possible because of L1’s conserved adenosine-rich coding sequences that are bound by SAFB proteins. The suppressive activity of SAFB extends to tissue-specific, giant protein-coding cassette exons, nested genes and Tigger DNA transposons. Moreover, SAFB also suppresses LTR/ERV elements in species in which they are still active, such as mice and flies. A significant subset of splicing events suppressed by SAFB in somatic cells are activated in the testis, coinciding with low SAFB expression in postmeiotic spermatids. Reminiscent of the division of labour between innate and adaptive immune systems that fight external pathogens, our results uncover SAFB proteins as an RNA-based, pattern-guided, non-adaptive defence system against TEs in the soma, complementing the RNA-based, adaptive Piwi-interacting RNA pathway of the germline.
Rainforest transformation reallocates energy from green to brown food webs
Authors: Potapov Anton M. , Drescher Jochen , Darras Kevin , Wenzel Arne , Janotta Noah , Nazarreta Rizky , Kasmiatun  , Laurent Valentine , Mawan Amanda , Utari Endah H. , Pollierer Melanie M. , Rembold Katja , Widyastuti Rahayu , Buchori Damayanti , Hidayat Purnama , Turner Edgar , Grass Ingo , Westphal Catrin , Tscharntke Teja , Scheu Stefan
Published: February 2024

Terrestrial animal biodiversity is increasingly being lost because of land-use change1,2. However, functional and energetic consequences aboveground and belowground and across trophic levels in megadiverse tropical ecosystems remain largely unknown. To fill this gap, we assessed changes in energy fluxes across ‘green’ aboveground (canopy arthropods and birds) and ‘brown’ belowground (soil arthropods and earthworms) animal food webs in tropical rainforests and plantations in Sumatra, Indonesia. Our results showed that most of the energy in rainforests is channelled to the belowground animal food web. Oil palm and rubber plantations had similar or, in the case of rubber agroforest, higher total animal energy fluxes compared to rainforest but the key energetic nodes were distinctly different: in rainforest more than 90% of the total animal energy flux was channelled by arthropods in soil and canopy, whereas in plantations more than 50% of the energy was allocated to annelids (earthworms). Land-use change led to a consistent decline in multitrophic energy flux aboveground, whereas belowground food webs responded with reduced energy flux to higher trophic levels, down to −90%, and with shifts from slow (fungal) to fast (bacterial) energy channels and from faeces production towards consumption of soil organic matter. This coincides with previously reported soil carbon stock depletion3. Here we show that well-documented animal biodiversity declines with tropical land-use change4–6 are associated with vast energetic and functional restructuring in food webs across aboveground and belowground ecosystem compartments.
Visuo-frontal interactions during social learning in freely moving macaques
Authors: Franch Melissa , Yellapantula Sudha , Parajuli Arun , Kharas Natasha , Wright Anthony , Aazhang Behnaam , Dragoi Valentin
Published: February 2024

Social interactions represent a ubiquitous aspect of our everyday life that we acquire by interpreting and responding to visual cues from conspecifics1. However, despite the general acceptance of this view, how visual information is used to guide the decision to cooperate is unknown. Here, we wirelessly recorded the spiking activity of populations of neurons in the visual and prefrontal cortex in conjunction with wireless recordings of oculomotor events while freely moving macaques engaged in social cooperation. As animals learned to cooperate, visual and executive areas refined the representation of social variables, such as the conspecific or reward, by distributing socially relevant information among neurons in each area. Decoding population activity showed that viewing social cues influences the decision to cooperate. Learning social events increased coordinated spiking between visual and prefrontal cortical neurons, which was associated with improved accuracy of neural populations to encode social cues and the decision to cooperate. These results indicate that the visual-frontal cortical network prioritizes relevant sensory information to facilitate learning social interactions while freely moving macaques interact in a naturalistic environment.
Seismic landslide susceptibility assessment using principal component analysis and support vector machine
Authors: Xu Ziyao , Che Ailan , Zhou Hanxu
Published: February 2024

Seismic landslides are dangerous natural hazards that can cause immense damage to human lives and property. Susceptibility assessment of earthquake-triggered landslides provides the scientific basis and theoretical foundation for disaster emergency management in engineering projects. However, landslide susceptibility assessment requires a massive amount of historical landslide data. Evidence of past landslide activities may be lost due to changes in geographical conditions and human factors over time. The lack of landslide data poses difficulties in assessing landslide susceptibility. The aim of this study is to establish a generalized seismic landslide susceptibility assessment model for applying it to the Dayong highway in the Chenghai area, where earthquakes occur frequently but with a lack of landslide data. The landslide data used comes from the 2014 Ludian Ms (Surface wave magnitude) 6.5 earthquake in a region with geographical conditions similar to those in the Chenghai area. The influencing factors considered include elevation, slope, slope aspect, distance to streams, distance to faults, geology, terrain wetness index, normalized difference vegetation index, epicenter distance and peak ground acceleration. The frequency ratio method is used to eliminate influencing factors with poor statistical dispersion of landslides. Principal component analysis (PCA) is utilized to reduce the dimensionality of landslide conditioning factors and to improve the transferability of the assessment model to different regions. A support vector machine model is used to establish the susceptibility assessment model. The results show that the accuracy of the PCA–SVM model reaches 93.6%. The landslide susceptibility of the Chenghai area is classified into 5 classes, with the “Very high” landslide susceptibility class accounting for 0.63%. The 13-km section in the middle of the Dayong highway, which accounts for 8.9%, is identified as the high-risk area most obviously impacted by seismic landslides. This study provides a new approach for seismic landslide susceptibility assessment in areas lacking in landslide inventory data.
Assessing respiratory epidemic potential in French hospitals through collection of close contact data (April–June 2020)
Authors: Shirreff George , Huynh Bich-Tram , Duval Audrey , Pereira Lara Cristina , Annane Djillali , Dinh Aurélien , Lambotte Olivier , Bulifon Sophie , Guichardon Magali , Beaune Sebastien , Toubiana Julie , Kermorvant-Duchemin Elsa , Chéron Gerard , Cordel Hugues , Argaud Laurent , Douplat Marion , Abraham Paul , Tazarourte Karim , Martin-Gaujard Géraldine , Vanhems Philippe , Hilliquin Delphine , Nguyen Duc , Chelius Guillaume , Fraboulet Antoine ,   EMAE-MESuRS Working Group on Nosocomial SARS-CoV-2 Modelling, Temime Laura , Opatowski Lulla , Guillemot Didier
Published: February 2024

The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). However, epidemic risk across wards is still poorly described. We measured CPIs directly using wearable sensors given to all present in a clinical ward over a 36-h period, across 15 wards in three hospitals in April-June 2020. Data were collected from 2114 participants and combined with a simple transmission model describing the arrival of a single index case to the ward to estimate the risk of an outbreak. Estimated epidemic risk ranged four-fold, from 0.12 secondary infections per day in an adult emergency to 0.49 per day in general paediatrics. The risk presented by an index case in a patient varied 20-fold across wards. Using simulation, we assessed the potential impact on outbreak risk of targeting the most connected individuals for prevention. We found that targeting those with the highest cumulative contact hours was most impactful (20% reduction for 5% of the population targeted), and on average resources were better spent targeting patients. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk.
Nanoengineered chitosan functionalized titanium dioxide biohybrids for bacterial infections and cancer therapy
Authors: Shabib Akhtar Mohammad , Chandrasekaran Karthikeyan , Saminathan Sharmila , Rajalingam Siva Ranjani , Mohsin Nehal , Awad Alkarem Ahmed Khalid Altigani , Alhazmi Yasir , Walbi Ismail A. , Abdel-Wahab Basel A. , Gholap Amol D. , Faiyazuddin Md. , Sundaram Gowri
Published: February 2024

Nanoengineered chitosan functionalized titanium dioxide biohybrids (CTiO2@NPs) were prepared with Amomum subulatum Roxb extract via one-pot green method and assessed by UV–Vis spectroscopy, XRD, SEM and EDAX analyses. As revealed by XRD pattern, the nanohybrids exhibits a rutile TiO2 crystallites around 45 nm in size. The emergence of the Ti–O–Ti bond is identified by observing a peak between 400 and 800 cm−1. A wide bandgap (4.8 eV) has been observed in CTiO2@NPs, due to the quantum confinement effects and the oxygen vacancies reveal the intriguing potential of developed nanohybrids for various applications. Surface flaws were identified by observing an emission band at 382, 437, 482, 517, and 556 nm. They also exhibit better antibacterial performances using well diffusion method against Staphylococcus aureus, Bacillus substilis, Klebsiella pneumonia, and Escherichia coli. CTiO2@NPs were discovered to have free radical scavenging activity on DPPH analysis and exhibit IC50 value as 95.80 μg/mL and standard (Vitamin C) IC50 is 87.62 μg/mL. CTiO2@NPs exhibited better anticancer properties against the osteosarcoma (MG-63) cell line. All these findings suggest that there is a forum for further useful therapeutic applications. Therefore, we claim that nano-engineered carbohydrated TiO2 phytohybrid is a promising solution for bacterial infections and bone cancer.
Monte Carlo simulations of spherocylinders interacting with site-dependent square-well potentials
Authors: Yellam Kiranmai , Priyadarshi Anshuman , Jha Prateek K.
Published: February 2024

Monte Carlo simulations are performed to study the self-assembly of a dilute system of spherocylinders interacting with square-well potential. The interactions are defined between randomly placed sites on the axis of the spherocylinder, akin to the interacting groups on a rigid rodlike molecule. This model therefore also serves as a minimal coarse-grained representation of a system of low molecular weight or stiff polymers with contour lengths significantly lower than the persistence length, interacting predominantly with short-range interactions (e.g., hydrogen bonding). The spherocylinder concentration, square-well interaction strength and range, and fraction of interacting sites are varied to study the phase behavior of the system. We observe the formation of dispersed, bundled, and network configurations of the system that may be compared with previous atomistic simulation results of weak polyelectrolytes.
Apolipoprotein L1 (APOL1) renal risk variant-mediated podocyte cytotoxicity depends on African haplotype and surface expression
Authors: Gupta Nidhi , Waas Bridget , Austin Daniel , De Mazière Ann M. , Kujala Pekka , Stockwell Amy D. , Li Tianbo , Yaspan Brian L. , Klumperman Judith , Scales Suzie J.
Published: February 2024

Homozygous Apolipoprotein L1 (APOL1) variants G1 and G2 cause APOL1-mediated kidney disease, purportedly acting as surface cation channels in podocytes. APOL1-G0 exhibits various single nucleotide polymorphisms, most commonly haplotype E150K, M228I and R255K (“KIK”; the Reference Sequence is “EMR”), whereas variants G1 and G2 are mostly found in a single “African” haplotype background (“EIK”). Several labs reported cytotoxicity with risk variants G1 and G2 in KIK or EIK background haplotypes, but used HEK-293 cells and did not verify equal surface expression. To see if haplotype matters in a more relevant cell type, we induced APOL1-G0, G1 and G2 EIK, KIK and EMR at comparable surface levels in immortalized podocytes. G1 and G2 risk variants (but not G0) caused dose-dependent podocyte death within 48h only in their native African EIK haplotype and correlated with K+ conductance (thallium FLIPR). We ruled out differences in localization and trafficking, except for possibly greater surface clustering of cytotoxic haplotypes. APOL1 surface expression was required, since Brefeldin A rescued cytotoxicity; and cytoplasmic isoforms vB3 and vC were not cytotoxic. Thus, APOL1-EIK risk variants kill podocytes in a dose and haplotype-dependent manner (as in HEK-293 cells), whereas unlike in HEK-293 cells the KIK risk variants did not.
Changes of physicochemical and functional properties of processed cheese made with natural cheddar and mozzarella cheeses during refrigerated storage
Authors: Liu Tongji , Wu Jingwei , Aziz Tariq , Xue Rui , Khowdiary Manal M. , Yang Zhennai
Published: February 2024

The present study aimed to investigate changes of physicochemical and functional properties of the processed cheeses (PCs) made with Cheddar (PC1), Mozzarella (PC2) and both of them at a ratio of 1:1 (PC3) during storage at 4 °C for 4 months. The results showed that the type of natural cheese used affected the composition of PCs with lower fat content in PC2 due to the lower fat content of Mozzarella cheese used. PC2 with lower fat content showed decreased meltability and oil leakage compared with PC1 and PC3. The stretchability of all the samples significantly (P < 0.05) decreased during storage, and PC1 showed lower stretchability. This was confirmed by increased protein hydrolysis of all the samples during the storage with a higher level of proteolysis in PC1, leading to decreased stretchability of PCs. Further low-field nuclear magnetic resonance analysis indicated more entrapped water in cheese due to moisture migration into the cheese matrix that might squeeze the fat globules to aggregate, causing more fat leakage during later stages of storage. This was evidenced by microstructural analysis showing different extents of increase in fat particle sizes and decrease in free serum in all the PC samples over the storage time. Therefore, the present study provides further understanding of the mechanism of quality change of PC during refrigerated storage as affected by proteolytic properties and composition of natural cheese used.
Bifidobacterium longum 1714 improves sleep quality and aspects of well-being in healthy adults: a randomized, double-blind, placebo-controlled clinical trial
Authors: Patterson Elaine , Tan Hern Tze Tina , Groeger David , Andrews Mark , Buckley Martin , Murphy Eileen F. , Groeger John A.
Published: February 2024

Stress and sleep are linked with overall well-being.Bifidobacterium longum1714 has been shown to influence stress responses and modulate neural responses during social stress, and influence sleep quality during examination stress in healthy adults. Here, we explored the ability of this strain to alter sleep quality in adults using subjective and objective measures. Eighty-nine adults (18–45y) with impaired sleep quality assessed with the Pittsburgh Sleep Quality Index (PSQI) and with a global score ≥ 5 were randomized to receiveB. longum1714 or placebo daily for eight weeks. Assessing the effect of the strain on PSQI global score was the primary objective. Secondary objectives assessed sleep quality and well-being subjectively and sleep parameters using actigraphy objectively. While PSQI global score improved in both groups,B. longum1714 significantly improved the PSQI component of sleep quality (p < 0.05) and daytime dysfunction due to sleepiness (p < 0.05) after 4 weeks and social functioning (p < 0.05) and energy/vitality (p < 0.05) after 8 weeks, compared to placebo. No significant effect on actigraphy measures were observed. The 1714 strain had a mild effect on sleep, demonstrated by a faster improvement in sleep quality at week 4 compared to placebo, although overall improvements after 8 weeks were similar in both groups.B. longum1714 improved social functioning and increased energy/vitality in line with previous work that showed the strain modulated neural activity which correlated with enhanced vitality/reduced mental fatigue (ClinicalTrials.gov: NCT04167475).
Immunological mechanisms of the nucleocapsid protein in COVID-19
Authors: Edalat Fahime , Khakpour Niloofar , Heli Hossein , Letafati Arash , Ramezani Amin , Hosseini Seyed Younes , Moattari Afagh
Published: February 2024

The emergence of corona virus disease 2019 (COVID-19), resulting from Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has left an indelible mark on a global scale, causing countless infections and fatalities. This investigation delves into the role of the SARS-CoV-2 nucleocapsid (N) protein within the HEK293 cells, shedding light on its influence over apoptosis, interferon signaling, and cytokines production. The N gene was amplified, inserted into the pAdTrack-CMV vector, and then transfected to the HEK293 cells. Changes in the expression of IRF3, IRF7, IFN-β, BAK, BAX, and BCL-2 genes were evaluated. The levels of proinflammatory cytokines of IL-6, IL-12, IL-1β, and TNF-α were also determined. The N protein exhibited an anti-apoptotic effect by modulating critical genes associated with apoptosis, including BAK, BAX, and BCL-2. This effect potentially prolonged the survival of infected cells. The N protein also played a role in immune evasion by suppressing the interferon pathway, evidenced by the downregulation of essential interferon regulatory factors of IRF3 and IRF7, and IFN-β expression. The N protein expression led to a substantial increase in the production of proinflammatory cytokines of IL-6, IL-12, IL-1β, and TNF-α. The N protein emerged as a versatile factor and was exerted over apoptosis, interferon signaling, and cytokine production. These findings carry potential implications for the development of targeted therapies to combat COVID-19 and mitigate its global health impact.
An open-source, 3D printed inkjet DNA synthesizer
Authors: Kim Junhyeong , Kim Haeun , Bang Duhee
Published: February 2024

Synthetic oligonucleotides have become a fundamental tool in a wide range of biological fields, including synthetic biology, biosensing, and DNA storage. Reliable access to equipment for synthesizing high-density oligonucleotides in the laboratory ensures research security and the freedom of research expansion. In this study, we introduced the Open-Source Inkjet DNA Synthesizer (OpenIDS), an open-source inkjet-based microarray synthesizer that offers ease of construction, rapid deployment, and flexible scalability. Utilizing 3D printing, Arduino, and Raspberry Pi, this newly designed synthesizer achieved robust stability with an industrial inkjet printhead. OpenIDS maintains low production costs and is therefore suitable for self-fabrication and optimization in academic laboratories. Moreover, even non-experts can create and control the synthesizer with a high degree of freedom for structural modifications. Users can easily add printheads or alter the design of the microarray substrate according to their research needs. To validate its performance, we synthesized oligonucleotides on 144 spots on a 15 × 25-mm silicon wafer filled with controlled pore glass. The synthesized oligonucleotides were analyzed using urea polyacrylamide gel electrophoresis.
Airborne imagery does not preclude detectability issues in estimating bird colony size
Authors: Couturier Thibaut , Gaillard Laurie , Vadier Almodis , Dautrey Emilien , Mathey Jérôme , Besnard Aurélien
Published: February 2024

Aerial images obtained by drones are increasingly used for ecological research such as wildlife monitoring. Yet detectability issues resulting from animal activity or visibility are rarely considered, although these may lead to biased population size and trend estimates. In this study, we investigated detectability in a census of Malagasy pond heron Ardeola idae colonies on the island of Mayotte. We conducted repeated drone flights over breeding colonies in mangrove habitats during two breeding seasons. We then identified individuals and nests in the images and fitted closed capture-recapture models on nest-detection histories. We observed seasonal variation in the relative abundance of individuals, and intra-daily variation in the relative abundance of individuals—especially immature birds—affecting the availability of nests for detection. The detection probability of nests estimated by capture–recapture varied between 0.58 and 0.74 depending on flyover days and decreased 25% from early to late morning. A simulation showed that three flyovers are necessary to detect a 5–6% decline in colonies of 50 to 200 nests. These results indicate that the detectability of nests of forest-canopy breeding species from airborne imagery can vary over space and time; we recommend the use of capture-recapture methods to control for this bias.
Spatial sequestration of activated-caspase 3 in aggresomes mediates resistance of neuroblastoma cell to bortezomib treatment
Authors: Berthenet Kévin , Aïmontché Eliézer , El Mrini Sara , Brière Johan , Pion Nathalie , Iacono Isabelle , Brejon Stéphanie , Monier Karine , Catez Frédéric , Ichim Gabriel , Combaret Valérie , Mertani Hichem C. , Diaz Jean-Jacques , Albaret Marie Alexandra
Published: February 2024

Neuroblastoma (NB) is the most common pediatric tumor and is currently treated by several types of therapies including chemotherapies, such as bortezomib treatment. However, resistance to bortezomib is frequently observed by mechanisms that remain to be deciphered. Bortezomib treatment leads to caspase activation and aggresome formation. Using models of patients-derived NB cell lines with different levels of sensitivity to bortezomib, we show that the activated form of caspase 3 accumulates within aggresomes of NB resistant cells leading to an impairment of bortezomib-induced apoptosis and increased cell survival. Our findings unveil a new mechanism of resistance to chemotherapy based on an altered subcellular distribution of the executioner caspase 3. This mechanism could explain the resistance developed in NB patients treated with bortezomib, emphasizing the potential of drugs targeting aggresomes.
An animal study on the effectiveness of platelet-rich plasma as a direct pulp capping agent
Authors: Elkady Dina M. , Helaly Yara R. , El Fayoumy Hala W. , AbuBakr Huda O. , Yassin Aya M. , AbdElkader Naglaa A. , Farag Dina B. E. , El Aziz Possy M. Abd , Scarano Antonio , Khater Ahmad G. A.
Published: February 2024

Direct pulp capping (DPC) is a conservative approach for preserving tooth vitality without requiring more invasive procedures by enhancing pulp healing and mineralized tissue barrier formation. We investigated the effectiveness of Platelet Rich Plasma (PRP) vs. Mineral Trioxide Aggregate (MTA) as a DPC agent. Forty-two teeth from three mongrel dogs were divided into two equal groups. After three months, the animals were sacrificed to evaluate teeth radiographically using cone-beam computerized tomography, histopathologically, and real-time PCR for dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), and nestin (NES) mRNA expression. Radiographically, hard tissue formation was evident in both groups without significant differences (p = 0.440). Histopathologic findings confirmed the dentin bridge formation in both groups; however, such mineralized tissues were homogenous without cellular inclusions in the PRP group, while was osteodentin type in the MTA group. There was no significant difference in dentin bridge thickness between the PRP-capped and MTA-capped teeth (p = 0.732). The PRP group had significantly higher DSPP, MEPE, and NES mRNA gene expression than the MTA group (p < 0.05). In conclusion, PRP enables mineralized tissue formation following DPC similar to MTA, and could generate better cellular dentinogenic responses and restore dentin with homogenous architecture than MTA, making PRP a promising alternative DPC agent.
Assessment of deep learning segmentation for real-time free-breathing cardiac magnetic resonance imaging at rest and under exercise stress
Authors: Schilling Martin , Unterberg-Buchwald Christina , Lotz Joachim , Uecker Martin
Published: February 2024

In recent years, a variety of deep learning networks for cardiac MRI (CMR) segmentation have been developed and analyzed. However, nearly all of them are focused on cine CMR under breathold. In this work, accuracy of deep learning methods is assessed for volumetric analysis (via segmentation) of the left ventricle in real-time free-breathing CMR at rest and under exercise stress. Data from healthy volunteers (n = 15) for cine and real-time free-breathing CMR at rest and under exercise stress were analyzed retrospectively. Exercise stress was performed using an ergometer in the supine position. Segmentations of two deep learning methods, a commercially available technique (comDL) and an openly available network (nnU-Net), were compared to a reference model created via the manual correction of segmentations obtained with comDL. Segmentations of left ventricular endocardium (LV), left ventricular myocardium (MYO), and right ventricle (RV) are compared for both end-systolic and end-diastolic phases and analyzed with Dice’s coefficient. The volumetric analysis includes the cardiac function parameters LV end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV ejection fraction (EF), evaluated with respect to both absolute and relative differences. For cine CMR, nnU-Net and comDL achieve Dice’s coefficients above 0.95 for LV and 0.9 for MYO, and RV. For real-time CMR, the accuracy of nnU-Net exceeds that of comDL overall. For real-time CMR at rest, nnU-Net achieves Dice’s coefficients of 0.94 for LV, 0.89 for MYO, and 0.90 for RV and the mean absolute differences between nnU-Net and the reference are 2.9 mL for EDV, 3.5 mL for ESV, and 2.6% for EF. For real-time CMR under exercise stress, nnU-Net achieves Dice’s coefficients of 0.92 for LV, 0.85 for MYO, and 0.83 for RV and the mean absolute differences between nnU-Net and reference are 11.4 mL for EDV, 2.9 mL for ESV, and 3.6% for EF. Deep learning methods designed or trained for cine CMR segmentation can perform well on real-time CMR. For real-time free-breathing CMR at rest, the performance of deep learning methods is comparable to inter-observer variability in cine CMR and is usable for fully automatic segmentation. For real-time CMR under exercise stress, the performance of nnU-Net could promise a higher degree of automation in the future.
The effect of a startle-eliciting device on the foraging success of individual harbor seals (Phoca vitulina)
Authors: McKeegan Kathleen A. , Clayton Kate , Williams Rob , Ashe Erin , Reiss Stephanie , Mendez-Bye Andrea , Janik Vincent M. , Goetz Thomas , Zinkgraf Matthew , Acevedo-Gutiérrez Alejandro
Published: February 2024

Pinniped predation on commercially and ecologically important prey has been a source of conflict for centuries. In the Salish Sea, harbor seals (Phoca vitulina) are suspected of impeding the recovery of culturally and ecologically critical Pacific salmon (Oncorhynchus spp.). In Fall 2020, a novel deterrent called Targeted Acoustic Startle Technology (TAST) was deployed at Whatcom Creek to deter harbor seals from preying on fall runs of hatchery chum (O. keta) and Chinook (O. tshawytscha) salmon in Bellingham, Washington, USA. Field observations were conducted in 2020 to compare the presence and foraging success of individual harbor seals across sound exposure (TAST-on) and control (TAST-off) conditions. Observations conducted the previous (2019) and following (2021) years were used to compare the effects observed in 2020 to two control years. Using photo-identification, individual seals were associated with foraging successes across all 3 years of the study. Generalized linear mixed models showed a significant 45.6% reduction in the duration (min) individuals remained at the creek with TAST on, and a significant 43.8% reduction in the overall foraging success of individuals. However, the observed effect of TAST varied across individual seals. Seals that were observed regularly within one season were more likely to return the year after, regardless of TAST treatment. Generalized linear models showed interannual variation in the number of seals present and salmon consumed. However, the effect of TAST in 2020 was greater than the observed variation across years. Our analyses suggest TAST can be an effective tool for managing pinniped predation, although alternate strategies such as deploying TAST longer-term and using multi-unit setups to increase coverage could help strengthen its effects. Future studies should further examine the individual variability found in this study.
Explainable hybrid vision transformers and convolutional network for multimodal glioma segmentation in brain MRI
Authors: Zeineldin Ramy A. , Karar Mohamed E. , Elshaer Ziad , Coburger Jan , Wirtz Christian R. , Burgert Oliver , Mathis-Ullrich Franziska
Published: February 2024

Accurate localization of gliomas, the most common malignant primary brain cancer, and its different sub-region from multimodal magnetic resonance imaging (MRI) volumes are highly important for interventional procedures. Recently, deep learning models have been applied widely to assist automatic lesion segmentation tasks for neurosurgical interventions. However, these models are often complex and represented as “black box” models which limit their applicability in clinical practice. This article introduces new hybrid vision Transformers and convolutional neural networks for accurate and robust glioma segmentation in Brain MRI scans. Our proposed method, TransXAI, provides surgeon-understandable heatmaps to make the neural networks transparent. TransXAI employs a post-hoc explanation technique that provides visual interpretation after the brain tumor localization is made without any network architecture modifications or accuracy tradeoffs. Our experimental findings showed that TransXAI achieves competitive performance in extracting both local and global contexts in addition to generating explainable saliency maps to help understand the prediction of the deep network. Further, visualization maps are obtained to realize the flow of information in the internal layers of the encoder-decoder network and understand the contribution of MRI modalities in the final prediction. The explainability process could provide medical professionals with additional information about the tumor segmentation results and therefore aid in understanding how the deep learning model is capable of processing MRI data successfully. Thus, it enables the physicians’ trust in such deep learning systems towards applying them clinically. To facilitate TransXAI model development and results reproducibility, we will share the source code and the pre-trained models after acceptance athttps://github.com/razeineldin/TransXAI.
An action research study of quality improvement in instrument packaging procedures for the central sterile supply department
Authors: Pan Wei , Yi Liangying , Hu Ting , Huang Juanli , Huang Yongdeng
Published: February 2024

This study aimed to reduce instrument packaging defects in the Central Sterile Supply Department (CSSD) using action research. Data of the instrument packs packaged by the packaging personnel at the CSSD of the authors’ institution during March to May 2023 were collected and analyzed. After identifying the problems, 2 rounds of cyclic process of “plan-action-observe-reflect” were implemented to standardize the packaging procedures and develop and improve the applicable check of standard operating procedures for the CSSD. After strictly implementing the packaging operation standards and checklists, the number of packaging defect cases dropped from 274 to 41. A significant difference was identified between the number of packaging personnel who achieved a “pass” in the assessment of 3 items for maintenance. Also, 1 item for assembly had significant differences compared with the baseline number after the first cycle (P ≤ 0.001). A significant difference was identified between the number of packaging personnel who achieved a “pass” in the assessment of 20 items for 6 components after the second cycle compared with that after the first cycle (P ≤ 0.05). Through action research methodology, strict implementation of standardized packaging procedures in the CSSD can reduce packaging defects, thereby decreasing clinical complaints and ensuring patient safety.
Location-specific deviant responses to object sequences in macaque inferior temporal cortex
Authors: Esmailpour Hamideh , Vogels Rufin
Published: February 2024

Many species learn temporal regularities in their visual environment, demonstrating visual statistical learning. In this study, we explored the sensitivity of macaque inferior temporal (IT) cortical neurons to transition probabilities of sequentially presented visual images, presented at different locations in the visual field. We exposed monkeys to sequences of two images, where the first image was presented either foveally or peripherally, and the second image was consistently presented foveally. Following several weeks of exposure, we recorded IT responses to assess differences between the exposed (Fixed) and new, Deviant sequences, where the identity of the first image in a sequence differed from the exposure phase. While enhanced responses to Deviant sequences were observed when both images of a pair were foveally presented during exposure, no such deviant responses were present when the first image was presented peripherally. This finding challenges the notion that mere exposure to image sequences always leads to deviant responses in macaque IT. The results highlight the complexity of the mechanisms underlying statistical learning in primates, particularly in the context of peripheral image presentations, emphasizing the need for further investigation into the origins of these responses in the IT cortex.
Evaluate the value of prolonging the duration of tiopronin for injection administration in preventing hepatotoxicity
Authors: Yang Hongye , Lin Mingzhu , Liu Mengxing , Gu Huawei , Li Dan , Shi Yu , Hou Xidong
Published: February 2024

As part of supportive therapy, prophylaxis with tiopronin for injection (TI) against common hepatotoxicity complications has often been used. However, methods to prevent hepatotoxicity have not been established. Therefore, our study was aimed to find out the relationship between the periods of TI prophylaxis and post-treatment hepatotoxicity, and evaluated the value of prolonging the duration of TI administration in preventing hepatotoxicity. Hepatotoxicity was detected through liver transaminases, bilirubin, alkaline phosphatase, and clinical features of liver insufficiency. Multivariable logistic regressions were conducted to examine the association of the periods of TI prophylaxis and post-treatment hepatotoxicity. Between January 2022 and March 2023, a total of 452 patients with gynecological cancer were enrolled in the study, of which 93 (20.58%) participants were post-treatment hepatotoxicity positive. TI with different prevention days were no significant difference among participants with or without post-treatment hepatotoxicity in crude model (P > 0.05). The P-value, the odds ratios (OR) and 95% confidence intervals (CI) of participants with TI prophylaxis for 1 day for post-treatment hepatotoxicity were 0.040, 3.534 (1.061–11.765) in fully adjusted model. Past history of hepatotoxicity is a confounding variable, and there was no significant difference for post-treatment hepatotoxicity when stratified by past history of hepatotoxicity (P > 0.05). The study indicate that the periods of TI prophylaxis is not associated with post-treatment hepatotoxicity, suggesting that prolonged the periods of TI prophylaxis might be an invalid method for the prevention of post-treatment hepatotoxicity.
Bayesian active learning with model selection for spectral experiments
Authors: Nabika Tomohiro , Nagata Kenji , Mizumaki Masaichiro , Katakami Shun , Okada Masato
Published: February 2024

Active learning is a common approach to improve the efficiency of spectral experiments. Model selection from the candidates and parameter estimation are often required in the analysis of spectral experiments. Therefore, we proposed an active learning with model selection method using multiple parametric models as learning models. Important points for model selection and its parameter estimation were actively measured using Bayesian posterior distribution. The present study demonstrated the effectiveness of our proposed method for spectral deconvolution and Hamiltonian selection in X-ray photoelectron spectroscopy.