bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulus encoding by specific inactivation of cortical neurons
Authors: Pérez-Ortega Jesús , Akrouh Alejandro , Yuste Rafael 
Published: April 2024

AbstractNeuronal ensembles are groups of neurons with correlated activity associated with sensory, motor, and behavioral functions. To explore how ensembles encode information, we investigated responses of visual cortical neurons in awake mice using volumetric two-photon calcium imaging during visual stimulation. We identified neuronal ensembles employing an unsupervised model-free algorithm and, besides neurons activated by the visual stimulus (termed “onsemble”), we also find neurons that are specifically inactivated (termed “offsemble”). Offsemble neurons showed faster calcium decay during stimuli, suggesting selective inhibition. In response to visual stimuli, each ensemble (onsemble+offsemble) exhibited small trial-to-trial variability, high orientation selectivity, and superior predictive accuracy for visual stimulus orientation, surpassing the sum of individual neuron activity. Thus, the combined selective activation and inactivation of cortical neurons enhances visual encoding as an emergent and distributed neural code.
Subthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control
Authors: Bange Manuel , Gonzalez-Escamilla Gabriel , Herz Damian M. , Tinkhauser Gerd , Glaser Martin , Ciolac Dumitru , Pogosyan Alek , Kreis Svenja L. , Luhmann Heiko J. , Tan Huiling , Groppa Sergiu 
Published: April 2024

AbstractIncreasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson’s disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson’s disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson’s disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.
Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial
Authors: Yarchoan Mark , Gane Edward J. , Marron Thomas U. , Perales-Linares Renzo , Yan Jian , Cooch Neil , Shu Daniel H. , Fertig Elana J. , Kagohara Luciane T. , Bartha Gabor , Northcott Josette , Lyle John , Rochestie Sarah , Peters Joann , Connor Jason T. , Jaffee Elizabeth M. , Csiki Ildiko , Weiner David B. , Perales-Puchalt Alfredo , Sardesai Niranjan Y. 
Published: April 2024

AbstractProgrammed cell death protein 1 (PD-1) inhibitors have modest efficacy as a monotherapy in hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) may enhance responses to PD-1 inhibitors through the induction of tumor-specific immunity. We present results from a single-arm, open-label, phase 1/2 study of a DNA plasmid PTCV (GNOS-PV02) encoding up to 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab in patients with advanced HCC previously treated with a multityrosine kinase inhibitor. Safety and immunogenicity were assessed as primary endpoints, and treatment efficacy and feasibility were evaluated as secondary endpoints. The most common treatment-related adverse events were injection-site reactions, observed in 15 of 36 (41.6%) patients. No dose-limiting toxicities or treatment-related grade ≥3 events were observed. The objective response rate (modified intention-to-treat) per Response Evaluation Criteria in Solid Tumors 1.1 was 30.6% (11 of 36 patients), with 8.3% (3 of 36) of patients achieving a complete response. Clinical responses were associated with the number of neoantigens encoded in the vaccine. Neoantigen-specific T cell responses were confirmed in 19 of 22 (86.4%) evaluable patients by enzyme-linked immunosorbent spot assays. Multiparametric cellular profiling revealed active, proliferative and cytolytic vaccine-specific CD4+ and CD8+ effector T cells. T cell receptor β-chain (TCRβ) bulk sequencing results demonstrated vaccination-enriched T cell clone expansion and tumor infiltration. Single-cell analysis revealed posttreatment T cell clonal expansion of cytotoxic T cell phenotypes. TCR complementarity-determining region cloning of expanded T cell clones in the tumors following vaccination confirmed reactivity against vaccine-encoded neoantigens. Our results support the PTCV’s mechanism of action based on the induction of antitumor T cells and show that a PTCV plus pembrolizumab has clinical activity in advanced HCC. ClinicalTrials.gov identifier: NCT04251117.
Possible involvement of zinc transporter ZIP13 in myogenic differentiation
Authors: Shoji Masaki , Ohashi Takuto , Nagase Saki , Yuri Haato , Ichihashi Kenta , Takagishi Teruhisa , Nagata Yuji , Nomura Yuki , Fukunaka Ayako , Kenjou Sae , Miyake Hatsuna , Hara Takafumi , Yoshigai Emi , Fujitani Yoshio , Sakurai Hidetoshi , dos Santos Heloísa G. , Fukada Toshiyuki , Kuzuhara Takashi 
Published: April 2024

AbstractEhlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13G64D) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.
Isolation and propagation of an Egyptian Theileria annulata infected cell line and evaluation of its use as a vaccine to protect cattle against field challenge
Authors: AL-Hosary Amira , Radwan Ahmed M. , Ahmed Laila S. , Abdelghaffar Sary Kh. , Fischer Susanne , Nijhof Ard M. , Clausen Peter-Henning , Ahmed Jabbar S. 
Published: April 2024

AbstractTropical theileriosis is an important protozoan tick-borne disease in cattle. Vaccination using attenuated schizont-infected cell lines is one of the methods used for controlling the disease. This study describes the production of attenuated schizont-infected cell lines from Egypt and an evaluation of its use as a vaccine to protect calves against clinical disease upon field challenge. Two groups of exotic and crossbred male calves were divided into vaccinated and control groups. The vaccinated groups were inoculated with 4 ml (1 × 106 cells/ml) of the attenuated cell line. Three weeks after vaccination, calves of both groups were transported to the New Valley Governorate (Egyptian oasis) where they were kept under field conditions and exposed to the natural Theileria annulata challenge. All animals in the control group showed severe clinical signs and died despite treatment with buparvaquone, which was administered after two days of persistent fever due to a severe drop in packed cell volume (PCV). Animals in the vaccinated group became seropositive without developing severe clinical signs other than transient fever. Post-mortem examinations revealed enlarged and fragile lymph nodes, spleen, and liver with necrosis and hemorrhages. These findings indicate that the Egyptian attenuated cell line was successful in protecting both exotic and crossbred animals against tropical theileriosis under field conditions.
Porous sulfur polymers for effective aqueous-phase organic contaminant removal
Authors: Diniz Vinicius , Bear Joseph C. , Rath Susanne , Crick Colin R. 
Published: April 2024

AbstractSulfur polymers produced through 'inverse vulcanization' exhibit various attributes, such as photocatalytic activity and a high capacity to adsorb heavy metals. Nevertheless, there is a lack of research investigating the use of sulfur polymers as materials for the removal of organic contaminants. In this work, porous sulfur polymers (PSPs) were synthesized from elemental sulfur and 1,3-diisopropenylbenzene, with porosity introduced via salt templating. The result is a material that can strongly adsorb and chemically neutralize a model organic contaminant (caffeine). PSPs show adsorption up to 5 times higher than a leading adsorption material (activated carbon). Furthermore, either the adsorption or degradation processes can govern the removal efficiency depending on the synthesis parameters of PSPs. This is the first-ever report demonstrating sulfur polymers as effective materials for removing emerging contaminants from water. The versatile synthesis of sulfur polymers offers variation, which means that there is much more to explore in this exciting research area.
Quantum biochemical analysis of the TtgR regulator and effectors
Authors: de Carvalho Matias E. G. , Bezerra K. S. , Costa A. H. Lima , Clemente Junior W. S. , Oliveira J. I. N. , Ribeiro Junior L. A. , Galvão D. S. , Fulco U. L. 
Published: April 2024

AbstractThe recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.
A comprehensive investigation of Bi2O3 on the physical, structural, optical, and electrical properties of K2O.ZnO.V2O5.B2O3 glasses
Authors: Ibrahim S. , Ali A. A. , Fathi Ahlam M. 
Published: April 2024

AbstractThe multi-component glass system has a composition of 10K2O–10ZnO–55 B2O3–(25–x)V2O5–xBi2O3 (x = 4, 5, 7.5, 9, 10 mol%) are synthesized by the melt-quenching method. Using X-ray diffraction examination, the amorphous phase in the material was confirmed. The physical characteristics of the produced compositions are examined using density (D) and molar volume (Vm). Calculations of physical properties showed that adding Bi2O3 from 4 to 10 mol% increased the glass density from 2.7878 to 3.3617 g cm−3 and decreased the molar volume from 40.4196 to 38.5895 cm3/mol. Studies of glass samples using the FTIR show bands of absorption for oxides in different structural groups. Octahedral [$${{\text{BiO}}}_{6}$$

BiO
6

], [$${{\text{BO}}}_{4}$$

BO
4

], and tetrahedral [$${{\text{BO}}}_{3}$$

BO
3

] structural units are observed in the present glass matrices. The cutoff wavelength ($${\lambda }_{C}$$

λ
C

), and optical band gap energy were determined using UV absorption spectra. The increase in non-bridging oxygens can be linked to the decrease in optical band gap energy ($${E}_{opt}$$

E

opt

) (direct and indirect) and the increase in cutoff wavelength with an increase in Bi2O3 content. This is attributed to the existence of bismuth ions and the creation of non-bridging oxygens. Besides that, the values of optical parameters, viz., optical electronegativity, refractive index, and molar refractivity, are calculated. The metallization criterion values are less than 1 and the glass samples exhibit an increased tendency towards metallization. Both the conductivity and the dielectric constant increase with the rise in Bi2O3 content, however, the dielectric loss and the impedance reduce. The behavior and values of conductivity for the studied glasses reveal the semiconducting properties of all glass samples. These results suggest that the produced glass samples may be employed as amorphous semiconductors in electronics and memory switching devices.
Continuous mowing differentially affects floral defenses in the noxious and invasive weed Solanum elaeagnifolium in its native range
Authors: Vasquez Alejandro , Alaniz Alexa , Dearth Robert , Kariyat Rupesh 
Published: April 2024

AbstractIn weeds, disturbance has been found to affect life history traits and mediate trophic interactions. In urban landscapes, mowing is an important disturbance, and we previously showed that continuous mowing leads to enhanced fitness and defense traits in Solanum elaeagnifolium, Silverleaf Nightshade (SLN). However, most studies have been focused on foliar defenses, ignoring floral defenses. In this study we examined whether continuous mowing affected floral defenses in SLN using mowed and unmowed populations in South Texas, their native range. We found flowers of mowed SLN plants larger but lighter than unmowed plants. Additionally, flowers on plants that were mowed frequently were both heavier and larger. Mowed plants had higher spine density and consequently unmowed flowers had higher herbivore damage. Additionally, early instar Manduca sexta fed on mowed flower-based artificial diets showed no difference in mass than the control and unmowed; however, later instars caterpillars on unmowed diets gained significantly more mass than the mowed treatment and control. Mowed plants had higher spine density which may shed light on why unmowed flowers experienced higher herbivore damage. We found caterpillars fed on high mowing frequency diets were heavier than those on low mowing frequency diets. Collectively, we show that mowing compromises floral traits and enhances plant defenses against herbivores and should be accounted for in management.
GIS-based intelligent planning approach of child-friendly pedestrian pathway to promote a child-friendly city
Authors: Fang Kailun , Azizan Suzana Ariff , Huang Huiming 
Published: April 2024

AbstractPedestrian safety, particularly for children, relies on well-designed pathways. Child-friendly pathways play a crucial role in safeguarding young pedestrians. Shared spaces accommodating both vehicles and walkers can bring benefits to pedestrians. However, active children playing near these pathways are prone to accidents. This research aims to develop an efficient method for planning child-friendly pedestrian pathways, taking into account community development and the specific needs of children. A mixed-methods approach was employed, utilizing the Datang community in Guangzhou, China, as a case study. This approach combined drawing techniques with GIS data analysis. Drawing methods were utilized to identify points of interest for children aged 2–6. The qualitative and quantitative fuzzy analytic hierarchy process assessed factors influencing pathway planning, assigning appropriate weights. The weighted superposition analysis method constructed a comprehensive cost grid, considering various community elements. To streamline the planning process, a GIS tool was developed based on the identified factors, resulting in a practical, child-friendly pedestrian pathway network. Results indicate that this method efficiently creates child-friendly pathways, ensuring optimal connectivity within the planned road network.
A study on expression recognition based on improved mobilenetV2 network
Authors: Zhu Qiming , Zhuang Hongwei , Zhao Mi , Xu Shuangchao , Meng Rui 
Published: April 2024

AbstractThis paper proposes an improved strategy for the MobileNetV2 neural network(I-MobileNetV2) in response to problems such as large parameter quantities in existing deep convolutional neural networks and the shortcomings of the lightweight neural network MobileNetV2 such as easy loss of feature information, poor real-time performance, and low accuracy rate in facial emotion recognition tasks. The network inherits the characteristics of MobilenetV2 depthwise separated convolution, signifying a reduction in computational load while maintaining a lightweight profile. It utilizes a reverse fusion mechanism to retain negative features, which makes the information less likely to be lost. The SELU activation function is used to replace the RELU6 activation function to avoid gradient vanishing. Meanwhile, to improve the feature recognition capability, the channel attention mechanism (Squeeze-and-Excitation Networks (SE-Net)) is integrated into the MobilenetV2 network. Experiments conducted on the facial expression datasets FER2013 and CK + showed that the proposed network model achieved facial expression recognition accuracies of 68.62% and 95.96%, improving upon the MobileNetV2 model by 0.72% and 6.14% respectively, and the parameter count decreased by 83.8%. These results empirically verify the effectiveness of the improvements made to the network model.
Visualisation of gene expression within the context of tissues using an X-ray computed tomography-based multimodal approach
Authors: Kairišs Kristaps , Sokolova Natalia , Zilova Lucie , Schlagheck Christina , Reinhardt Robert , Baumbach Tilo , Faragó Tomáš , van de Kamp Thomas , Wittbrodt Joachim , Weinhardt Venera 
Published: April 2024

AbstractThe development of an organism is orchestrated by the spatial and temporal expression of genes. Accurate visualisation of gene expression patterns in the context of the surrounding tissues offers a glimpse into the mechanisms that drive morphogenesis. We developed correlative light-sheet fluorescence microscopy and X-ray computed tomography approach to map gene expression patterns to the whole organism`s 3D anatomy. We show that this multimodal approach is applicable to gene expression visualized by protein-specific antibodies and fluorescence RNA in situ hybridisation offering a detailed understanding of individual phenotypic variations in model organisms. Furthermore, the approach offers a unique possibility to identify tissues together with their 3D cellular and molecular composition in anatomically less-defined in vitro models, such as organoids. We anticipate that the visual and quantitative insights into the 3D distribution of gene expression within tissue architecture, by multimodal approach developed here, will be equally valuable for reference atlases of model organisms development, as well as for comprehensive screens, and morphogenesis studies of in vitro models.
Adenosine triphosphate induces amorphous aggregation of amyloid β by increasing Aβ dynamics
Authors: Kuramochi Masahiro , Nakamura Momoka , Takahashi Hiroto , Komoriya Tomoe , Takita Teisuke , Pham Ngan Thi Kim , Yasukawa Kiyoshi , Yoshimune Kazuaki 
Published: April 2024

AbstractAmyloid β (Aβ) aggregates into two distinct fibril and amorphous forms in the brains of patients with Alzheimer’s disease. Adenosine triphosphate (ATP) is a biological hydrotrope that causes Aβ to form amorphous aggregates and inhibit fibril formation at physiological concentrations. Based on diffracted X-ray blinking (DXB) analysis, the dynamics of Aβ significantly increased immediately after ATP was added compared to those in the absence and presence of ADP and AMP, and the effect diminished after 30 min as the aggregates formed. In the presence of ATP, the β-sheet content of Aβ gradually increased from the beginning, and in the absence of ATP, the content increased rapidly after 180 min incubation, as revealed by a time-dependent thioflavin T fluorescence assay. Images of an atomic force microscope revealed that ATP induces the formation of amorphous aggregates with an average diameter of less than 100 nm, preventing fibrillar formation during 4 days of incubation at 37 °C. ATP may induce amorphous aggregation by increasing the dynamics of Aβ, and as a result, the other aggregation pathway is omitted. Our results also suggest that DXB analysis is a useful method to evaluate the inhibitory effect of fibrillar formation.