bluuebunny/crossref_metadata_2025_split huggingface dataset:
High temperature delays and low temperature accelerates evolution of a new protein phenotype
Authors: Zheng Jia , Guo Ning , Huang Yuxiang , Guo Xiang , Wagner Andreas 
Published: March 2024

AbstractSince the origin of life, temperatures on earth have fluctuated both on short and long time scales. How such changes affect the rate at which Darwinian evolution can bring forth new phenotypes remains unclear. On the one hand, high temperature may accelerate phenotypic evolution because it accelerates most biological processes. On the other hand, it may slow phenotypic evolution, because proteins are usually less stable at high temperatures and therefore less evolvable. Here, to test these hypotheses experimentally, we evolved a green fluorescent protein in E. coli towards the new phenotype of yellow fluorescence at different temperatures. Yellow fluorescence evolved most slowly at high temperature and most rapidly at low temperature, in contradiction to the first hypothesis. Using high-throughput population sequencing, protein engineering, and biochemical assays, we determined that this is due to the protein-destabilizing effect of neofunctionalizing mutations. Destabilization is highly detrimental at high temperature, where neofunctionalizing mutations cannot be tolerated. Their detrimental effects can be mitigated through excess stability at low temperature, leading to accelerated adaptive evolution. By modifying protein folding stability, temperature alters the accessibility of mutational paths towards high-fitness genotypes. Our observations have broad implications for our understanding of how temperature changes affect evolutionary adaptations and innovations.
Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum β-lactamase- and carbapenemase-producing bacteria
Authors: Nieto-Rosado Maria , Sands Kirsty , Portal Edward A. R. , Thomson Kathryn M. , Carvalho Maria J. , Mathias Jordan , Milton Rebecca , Dyer Calie , Akpulu Chinenye , Boostrom Ian , Hogan Patrick , Saif Habiba , Sanches Ferreira Ana D. , Hender Thomas , Portal Barbra , Andrews Robert , Watkins W. John , Zahra Rabaab , Shirazi Haider , Muhammad Adil , Ullah Syed Najeeb , Jan Muhammad Hilal , Akif Shermeen , Iregbu Kenneth C. , Modibbo Fatima , Uwaezuoke Stella , Audu Lamidi , Edwin Chinago P. , Yusuf Ashiru H. , Adeleye Adeola , Mukkadas Aisha S. , Mazarati Jean Baptiste , Rucogoza Aniceth , Gaju Lucie , Mehtar Shaheen , Bulabula Andrew N. H. , Whitelaw Andrew , Roberts Lauren , Chan Grace , Bekele Delayehu , Solomon Semaria , Abayneh Mahlet , Metaferia Gesit ,   Group BARNARDS, Walsh Timothy R. 
Published: March 2024

AbstractHospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum β-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.
Projective light-sheet microscopy with flexible parameter selection
Authors: Chen Bingying , Chang Bo-Jui , Daetwyler Stephan , Zhou Felix , Sharma Shiv , Lee Donghoon M. , Nayak Amruta , Noh Jungsik , Dubrovinski Konstantin , Chen Elizabeth H. , Glotzer Michael , Fiolka Reto 
Published: March 2024

AbstractProjection imaging accelerates volumetric interrogation in fluorescence microscopy, but for multi-cellular samples, the resulting images may lack contrast, as many structures and haze are summed up. Here, we demonstrate rapid projective light-sheet imaging with parameter selection (props) of imaging depth, position and viewing angle. This allows us to selectively image different sub-volumes of a sample, rapidly switch between them and exclude background fluorescence. Here we demonstrate the power of props by functional imaging within distinct regions of the zebrafish brain, monitoring calcium firing inside muscle cells of moving Drosophila larvae, super-resolution imaging of selected cell layers, and by optically unwrapping the curved surface of a Drosophila embryo. We anticipate that props will accelerate volumetric interrogation, ranging from subcellular to mesoscopic scales.
Development and crystal structures of a potent second-generation dual degrader of BCL-2 and BCL-xL
Authors: Nayak Digant , Lv Dongwen , Yuan Yaxia , Zhang Peiyi , Hu Wanyi , Nayak Anindita , Ruben Eliza A. , Lv Zongyang , Sung Patrick , Hromas Robert , Zheng Guangrong , Zhou Daohong , Olsen Shaun K. 
Published: March 2024

AbstractOverexpression of BCL-xL and BCL-2 play key roles in tumorigenesis and cancer drug resistance. Advances in PROTAC technology facilitated recent development of the first BCL-xL/BCL-2 dual degrader, 753b, a VHL-based degrader with improved potency and reduced toxicity compared to previous small molecule inhibitors. Here, we determine crystal structures of VHL/753b/BCL-xL and VHL/753b/BCL-2 ternary complexes. The two ternary complexes exhibit markedly different architectures that are accompanied by distinct networks of interactions at the VHL/753b-linker/target interfaces. The importance of these interfacial contacts is validated via functional analysis and informed subsequent rational and structure-guided design focused on the 753b linker and BCL-2/BCL-xL warhead. This results in the design of a degrader, WH244, with enhanced potency to degrade BCL-xL/BCL-2 in cells. Using biophysical assays followed by in cell activities, we are able to explain the enhanced target degradation of BCL-xL/BCL-2 in cells. Most PROTACs are empirically designed and lack structural studies, making it challenging to understand their modes of action and specificity. Our work presents a streamlined approach that combines rational design and structure-based insights backed with cell-based studies to develop effective PROTAC-based cancer therapeutics.
Enhancing combinatorial optimization with classical and quantum generative models
Authors: Alcazar Javier , Ghazi Vakili Mohammad , Kalayci Can B. , Perdomo-Ortiz Alejandro 
Published: March 2024

AbstractDevising an efficient exploration of the search space is one of the key challenges in the design of combinatorial optimization algorithms. Here, we introduce the Generator-Enhanced Optimization (GEO) strategy: a framework that leverages any generative model (classical, quantum, or quantum-inspired) to solve optimization problems. We focus on a quantum-inspired version of GEO relying on tensor-network Born machines, and referred to hereafter as TN-GEO. To illustrate our results, we run these benchmarks in the context of the canonical cardinality-constrained portfolio optimization problem by constructing instances from the S&P 500 and several other financial stock indexes, and demonstrate how the generalization capabilities of these quantum-inspired generative models can provide real value in the context of an industrial application. We also comprehensively compare state-of-the-art algorithms and show that TN-GEO is among the best; a remarkable outcome given the solvers used in the comparison have been fine-tuned for decades in this real-world industrial application. Also, a promising step toward a practical advantage with quantum-inspired models and, subsequently, with quantum generative models
Room temperature 3D carbon microprinting
Authors: Torres-Davila Fernand E. , Chagoya Katerina L. , Blanco Emma E. , Shahzad Saqib , Shultz-Johnson Lorianne R. , Mogensen Mirra , Gesquiere Andre , Jurca Titel , Rochdi Nabil , Blair Richard G. , Tetard Laurene 
Published: March 2024

AbstractManufacturing custom three-dimensional (3D) carbon functional materials is of utmost importance for applications ranging from electronics and energy devices to medicine, and beyond. In lieu of viable eco-friendly synthesis pathways, conventional methods of carbon growth involve energy-intensive processes with inherent limitations of substrate compatibility. The yearning to produce complex structures, with ultra-high aspect ratios, further impedes the quest for eco-friendly and scalable paths toward 3D carbon-based materials patterning. Here, we demonstrate a facile process for carbon 3D printing at room temperature, using low-power visible light and a metal-free catalyst. Within seconds to minutes, this one-step photocatalytic growth yields rod-shaped microstructures with aspect ratios up to ~500 and diameters below 10 μm. The approach enables the rapid patterning of centimeter-size arrays of rods with tunable height and pitch, and of custom complex 3D structures. The patterned structures exhibit appealing luminescence properties and ohmic behavior, with great potential for optoelectronics and sensing applications, including those interfacing with biological systems.
Nanoparticles targeting mutant p53 overcome chemoresistance and tumor recurrence in non-small cell lung cancer
Authors: Bi Yu-Yang , Chen Qiu , Yang Ming-Yuan , Xing Lei , Jiang Hu-Lin 
Published: March 2024

AbstractNon-small cell lung cancer (NSCLC) shows high drug resistance and leads to low survival due to the high level of mutated Tumor Protein p53 (TP53). Cisplatin is a first-line treatment option for NSCLC, and the p53 mutation is a major factor in chemoresistance. We demonstrate that cisplatin chemotherapy increases the risk of TP53 mutations, further contributing to cisplatin resistance. Encouragingly, we find that the combination of cisplatin and fluvastatin can alleviate this problem. Therefore, we synthesize Fluplatin, a prodrug consisting of cisplatin and fluvastatin. Then, Fluplatin self-assembles and is further encapsulated with poly-(ethylene glycol)–phosphoethanolamine (PEG–PE), we obtain Fluplatin@PEG–PE nanoparticles (FP NPs). FP NPs can degrade mutant p53 (mutp53) and efficiently trigger endoplasmic reticulum stress (ERS). In this study, we show that FP NPs relieve the inhibition of cisplatin chemotherapy caused by mutp53, exhibiting highly effective tumor suppression and improving the poor NSCLC prognosis.
Adhesion energy controls lipid binding-mediated endocytosis
Authors: Groza Raluca , Schmidt Kita Valerie , Müller Paul Markus , Ronchi Paolo , Schlack-Leigers Claire , Neu Ursula , Puchkov Dmytro , Dimova Rumiana , Matthaeus Claudia , Taraska Justin , Weikl Thomas R. , Ewers Helge 
Published: March 2024

AbstractSeveral bacterial toxins and viruses can deform membranes through multivalent binding to lipids for clathrin-independent endocytosis. However, it remains unclear, how membrane deformation and endocytic internalization are mechanistically linked. Here we show that many lipid-binding virions induce membrane deformation and clathrin-independent endocytosis, suggesting a common mechanism based on multivalent lipid binding by globular particles. We create a synthetic cellular system consisting of a lipid-anchored receptor in the form of GPI-anchored anti-GFP nanobodies and a multivalent globular binder exposing 180 regularly-spaced GFP molecules on its surface. We show that these globular, 40 nm diameter, particles bind to cells expressing the receptor, deform the plasma membrane upon adhesion and become endocytosed in a clathrin-independent manner. We explore the role of the membrane adhesion energy in endocytosis by using receptors with affinities varying over 7 orders of magnitude. Using this system, we find that once a threshold in adhesion energy is overcome to allow for membrane deformation, endocytosis occurs reliably. Multivalent, binding-induced membrane deformation by globular binders is thus sufficient for internalization to occur and we suggest it is the common, purely biophysical mechanism for lipid-binding mediated endocytosis of toxins and pathogens.
Gene-expression memory-based prediction of cell lineages from scRNA-seq datasets
Authors: Eisele A. S. , Tarbier M. , Dormann A. A. , Pelechano V. , Suter D. M. 
Published: March 2024

AbstractAssigning single cell transcriptomes to cellular lineage trees by lineage tracing has transformed our understanding of differentiation during development, regeneration, and disease. However, lineage tracing is technically demanding, often restricted in time-resolution, and most scRNA-seq datasets are devoid of lineage information. Here we introduce Gene Expression Memory-based Lineage Inference (GEMLI), a computational tool allowing to robustly identify small to medium-sized cell lineages solely from scRNA-seq datasets. GEMLI allows to study heritable gene expression, to discriminate symmetric and asymmetric cell fate decisions and to reconstruct individual multicellular structures from pooled scRNA-seq datasets. In human breast cancer biopsies, GEMLI reveals previously unknown gene expression changes at the onset of cancer invasiveness. The universal applicability of GEMLI allows studying the role of small cell lineages in a wide range of physiological and pathological contexts, notably in vivo. GEMLI is available as an R package on GitHub (https://github.com/UPSUTER/GEMLI).
Efficacy of deep brain stimulation of the subthalamic nucleus versus globus pallidus internus on sensory complaints
Authors: Ghilardi Maria Gabriela S. , Campos Ana Carolina P. , Cury Rubens G. , Martinez Raquel C. R. , Pagano Rosana L. , Fonoff Erich T. 
Published: March 2024

AbstractPain control after deep brain stimulation (DBS) in Parkinson’s disease (PD) remains unclear. Following six months, subthalamic (STN)-DBS reduced sensory complaints related to parkinsonism and bodily discomfort, increasing central beta-endorphin level. Pallidal GPi-DBS decreased bodily discomfort and beta-endorphin levels. Unexplained pain by other conditions and bodily discomfort were negatively correlated with beta-endorphin levels. Thus, DBS regulates central opioids, and prioritizing STN is important for PD patients with significant sensory complications.
Neuro-computing solution for Lorenz differential equations through artificial neural networks integrated with PSO-NNA hybrid meta-heuristic algorithms: a comparative study
Authors: Aslam Muhammad Naeem , Aslam Muhammad Waheed , Arshad Muhammad Sarmad , Afzal Zeeshan , Hassani Murad Khan , Zidan Ahmed M. , Akgül Ali 
Published: March 2024

AbstractIn this article, examine the performance of a physics informed neural networks (PINN) intelligent approach for predicting the solution of non-linear Lorenz differential equations. The main focus resides in the realm of leveraging unsupervised machine learning for the prediction of the Lorenz differential equation associated particle swarm optimization (PSO) hybridization with the neural networks algorithm (NNA) as ANN-PSO-NNA. In particular embark on a comprehensive comparative analysis employing the Lorenz differential equation for proposed approach as test case. The nonlinear Lorenz differential equations stand as a quintessential chaotic system, widely utilized in scientific investigations and behavior of dynamics system. The validation of physics informed neural network (PINN) methodology expands to via multiple independent runs, allowing evaluating the performance of the proposed ANN-PSO-NNA algorithms. Additionally, explore into a comprehensive statistical analysis inclusive metrics including minimum (min), maximum (max), average, standard deviation (S.D) values, and mean squared error (MSE). This evaluation provides found observation into the adeptness of proposed AN-PSO-NNA hybridization approach across multiple runs, ultimately improving the understanding of its utility and efficiency.
Modeling and development of technology for smelting a complex alloy (ligature) Fe-Si-Mn-Al from manganese-containing briquettes and high-ash coals
Authors: Nurumgaliyev Assylbek , Zhuniskaliyev Talgat , Shevko Viktor , Mukhambetgaliyev Yerbol , Kelamanov Bauyrzhan , Kuatbay Yerbol , Badikova Alexandra , Yerekeyeva Gauhar , Volokitina Irina 
Published: March 2024

AbstractInvestigation of the possibility of obtaining a complex master alloy used in the deoxidation of steel, smelted from substandard manganese-containing materials, briquettes, and high-ash coals in ore-thermal electric furnaces. Thermodynamic modeling was carried out using the HSC Chemistry software package to determine the optimal process parameters using a second-order rotatable plan (Box-Hunter plan). Thermodynamic modeling improves the understanding of physical and chemical processes, allows making predictions about the behavior of the system under various conditions, optimizing processes and saving time and resources necessary for experiments. Electric smelting of the briquette was carried out with coal and quartzite (to adjust the chemical composition and neutralize residual carbon) in an ore-thermal electric furnace with a power of up to 150 kV*A. The influence of temperature on the equilibrium distribution of silicon, manganese, and aluminum in the «briquette-coal-quartzite» system, the degree of transition of silicon and manganese into a complex ligature and the content of these metals in the alloy are determined by the method of thermodynamic modeling. As a result of experiments on ore-thermal electric smelting of a briquette with high-ash coal, a complex ligature was obtained with an average content of 45.92–53.11% silicon, 27.72–34.81% manganese and 5.60–6.91% aluminum.
Predictors of nirmatrelvir–ritonavir receipt among COVID-19 patients in a large US health system
Authors: Malden Deborah E. , McLaughlin John M. , Hong Vennis , Lewnard Joseph , Ackerson Bradley K. , Puzniak Laura , Kim Jeniffer S. , Takhar Harpreet , Frankland Timothy B. , Slezak Jeff M. , Tartof Sara Y. 
Published: March 2024

AbstractA clear understanding of real-world uptake of nirmatrelvir–ritonavir for treatment of SARS-CoV-2 can inform treatment allocation strategies and improve interpretation of effectiveness studies. We used data from a large US healthcare system to describe nirmatrelvir–ritonavir dispenses among all SARS-CoV-2 positive patients aged ≥ 12 years meeting recommended National Institutes of Health treatment eligibility criteria for the study period between 1 January and 31 December, 2022. Overall, 10.9% (N = 34,791/319,900) of treatment eligible patients with SARS-CoV-2 infections received nirmatrelvir–ritonavir over the study period. Although uptake of nirmatrelvir–ritonavir increased over time, by the end of 2022, less than a quarter of treatment eligible patients with SARS-CoV-2 infections had received nirmatrelvir–ritonavir. Across patient demographics, treatment was generally consistent with tiered treatment guidelines, with dispenses concentrated among patients aged ≥ 65 years (14,706/63,921; 23.0%), and with multiple comorbidities (10,989/54,431; 20.1%). However, neighborhoods of lower socioeconomic status (upper third of neighborhood deprivation index [NDI]) had between 12% (95% CI: 7–18%) and 28% (25–32%) lower odds of treatment dispense over the time periods studied compared to the lower third of NDI distribution, even after accounting for demographic and clinical characteristics. A limited chart review (N = 40) confirmed that in some cases a decision not to treat was appropriate and aligned with national guidelines to use clinical judgement on a case-by-case basis. There is a need to enhance patient and provider awareness on the availability and benefits of nirmatrelvir–ritonavir for the treatment of COVID-19 illness.
Torques in the human upper ankle joint level and their importance in conservative and surgical treatment
Authors: Dygut Jacek , Piwowar Monika 
Published: March 2024

AbstractThe paper deals with the torques of external muscles acting on the upper ankle joint under weight-bearing conditions and their importance in diagnosing and treating the human foot. Experimental data were collected and calculations were performed. Based on the experiments with the biomechanical model of the foot and upper ankle joint, it was shown how the changes in the force arms of the external muscles of the foot under weight-bearing conditions, change the torque. The real values of muscle forces and torques of the external muscles of the foot were calculated. Taking into account the distance of the lines of muscle action from the axis of rotation of the upper ankle joint the rotational force of the muscles was calculated. The influence of changing the force arm on the rotational efficiency of the muscle balancing the moment of gravity was shown. Knowledge of muscle torque under weight-bearing conditions is crucial for correctly assessing foot biomechanics. It has been shown that torque (gravitational and muscular), not pure force, is crucial when assessing the rotational capacity of the analyzed joint. A change in the approach to diagnostics and treating paresis or weakness of extrinsic foot muscles was proposed through the manipulation of the distance of their action line from the axis of joint rotation.
Expression and influence of KATP in umbilical artery smooth muscle cells of patients with hypertensive disorders of pregnancy
Authors: Yin Benlan , Yu Xiaotong , Fu Xiaodong , Liu Xiyuan , Xiao Jing , Yu Linli , Nie Yunying , Zhang Yujiao 
Published: March 2024

AbstractThe objective of this study is to investigate the expression and influence of adenosine triphosphate-sensitive potassium channel (KATP) in human umbilical arterial smooth muscle cells (HUASMCs) of patients with hypertensive disorders of pregnancy (HDP). Western blotting was used to detect the protein expression levels of KATP inwardly rectifying potassium channel (Kir)6.1 and sulphonylurea receptor (SUR)2B subunits in HUASMCs from patients with normal parturients (NP), gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE) and chronic hypertension with superimposed preeclampsia (CHSP), respectively. There was no significant difference in the protein expression of Kir6.1 subunit in NP group, GH group, CH group, PE group and CHSP group (P > 0.05). The protein expression of SUR2B subunit was gradually decreased in NP group, GH group, CH group, PE group and CHSP group, with statistically significant difference among the groups (P < 0.05). The altered expression level of KATP SUR2B subunit may be involved in the pathogenesis of HDP. The severity of HDP may be related to the degree of decrease of SUR2B subunit.