bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient evolution of human antibodies from general protein language models
Authors: Hie Brian L. , Shanker Varun R. , Xu Duo , Bruun Theodora U. J. , Weidenbacher Payton A. , Tang Shaogeng , Wu Wesley , Pak John E. , Kim Peter S. 
Published: April 2023

AbstractNatural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by suggesting mutations that are evolutionarily plausible, despite providing the model with no information about the target antigen, binding specificity or protein structure. We performed language-model-guided affinity maturation of seven antibodies, screening 20 or fewer variants of each antibody across only two rounds of laboratory evolution, and improved the binding affinities of four clinically relevant, highly mature antibodies up to sevenfold and three unmatured antibodies up to 160-fold, with many designs also demonstrating favorable thermostability and viral neutralization activity against Ebola and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, including antibiotic resistance and enzyme activity, suggesting that these results generalize to many settings.
A shared neural basis underlying psychiatric comorbidity
Authors: Xie Chao , Xiang Shitong , Shen Chun , Peng Xuerui , Kang Jujiao , Li Yuzhu , Cheng Wei , He Shiqi , Bobou Marina , Broulidakis M. John , van Noort Betteke Maria , Zhang Zuo , Robinson Lauren , Vaidya Nilakshi , Winterer Jeanne , Zhang Yuning , King Sinead , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L. W. , Bromberg Uli , Büchel Christian , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Ittermann Bernd , Lemaître Hervé , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Fröhner Juliane H. , Schmidt Ulrike , Sinclair Julia , Smolka Michael N. , Stringaris Argyris , Walter Henrik , Whelan Robert , Desrivières Sylvane , Sahakian Barbara J. , Robbins Trevor W. , Schumann Gunter , Jia Tianye , Feng Jianfeng ,   IMAGEN Consortium,   STRATIFY/ESTRA Consortium, van Noort Betteke Maria ,   ZIB Consortium
Published: April 2023

AbstractRecent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes. We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function. We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the STRATIFY & ESTRA Project). In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates. These findings may help to develop new therapeutic interventions for psychiatric comorbidities.
Computational complexity drives sustained deliberation
Authors: Hong Tao , Stauffer William R. 
Published: April 2023

AbstractEconomic deliberations are slow, effortful and intentional searches for solutions to difficult economic problems. Although such deliberations are critical for making sound decisions, the underlying reasoning strategies and neurobiological substrates remain poorly understood. Here two nonhuman primates performed a combinatorial optimization task to identify valuable subsets and satisfy predefined constraints. Their behavior revealed evidence of combinatorial reasoning—when low-complexity algorithms that consider items one at a time provided optimal solutions, the animals adopted low-complexity reasoning strategies. When greater computational resources were required, the animals approximated high-complexity algorithms that search for optimal combinations. The deliberation times reflected the demands created by computational complexity—high-complexity algorithms require more operations and, concomitantly, the animals deliberated for longer durations. Recurrent neural networks that mimicked low- and high-complexity algorithms also reflected the behavioral deliberation times and were used to reveal algorithm-specific computations that support economic deliberation. These findings reveal evidence for algorithm-based reasoning and establish a paradigm for studying the neurophysiological basis for sustained deliberation.
Tau activation of microglial cGAS–IFN reduces MEF2C-mediated cognitive resilience
Authors: Udeochu Joe C. , Amin Sadaf , Huang Yige , Fan Li , Torres Eileen Ruth S. , Carling Gillian K. , Liu Bangyan , McGurran Hugo , Coronas-Samano Guillermo , Kauwe Grant , Mousa Gergey Alzaem , Wong Man Ying , Ye Pearly , Nagiri Ravi Kumar , Lo Iris , Holtzman Julia , Corona Carlo , Yarahmady Allan , Gill Michael T. , Raju Ravikiran M. , Mok Sue-Ann , Gong Shiaoching , Luo Wenjie , Zhao Mingrui , Tracy Tara E. , Ratan Rajiv R. , Tsai Li-Huei , Sinha Subhash C. , Gan Li 
Published: April 2023

AbstractPathological hallmarks of Alzheimer’s disease (AD) precede clinical symptoms by years, indicating a period of cognitive resilience before the onset of dementia. Here, we report that activation of cyclic GMP–AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA. Genetic ablation of Cgas in mice with tauopathy diminished the microglial IFN-I response, preserved synapse integrity and plasticity and protected against cognitive impairment without affecting the pathogenic tau load. cGAS ablation increased, while activation of IFN-I decreased, the neuronal MEF2C expression network linked to cognitive resilience in AD. Pharmacological inhibition of cGAS in mice with tauopathy enhanced the neuronal MEF2C transcriptional network and restored synaptic integrity, plasticity and memory, supporting the therapeutic potential of targeting the cGAS–IFN–MEF2C axis to improve resilience against AD-related pathological insults.
Estimating GRACE terrestrial water storage anomaly using an improved point mass solution
Authors: Ferreira Vagner , Yong Bin , Montecino Henry , Ndehedehe Christopher E. , Seitz Kurt , Kutterer Hansjörg , Yang Kun 
Published: April 2023

AbstractThe availability of terrestrial water storage anomaly (TWSA) data from the Gravity Recovery and Climate Experiment (GRACE) supports many hydrological applications. Five TWSA products are operational and publicly available, including three based on mass concentration (mascon) solutions and two based on the synthesis of spherical harmonic coefficients (SHCs). The mascon solutions have advantages regarding the synthesis of SHCs since the basis functions are represented locally rather than globally, which allows geophysical data constraints. Alternative new solutions based on SHCs are, therefore, critical and warranted to enrich the portfolio of user-friendly TWSA data based on different algorithms. TWSA data based on novel processing protocols is presented with a spatial re-sampling of 0.25 arc-degrees covering 2002–2022. This approach parameterizes the improved point mass (IPM) and adopts the synthesized residual gravitational potential as observations. The assay indicates that the proposed Hohai University (HHU-) IPM TWSA data reliably agree with the mascon solutions. The presented HHU-IPM TWSA data set would be instrumental in regional hydrological applications, particularly enabling improved assessment of regional water budgets.
A novel visual illusion paradigm provides evidence for a general factor of illusion sensitivity and personality correlates
Authors: Makowski Dominique , Te An Shu , Kirk Stephanie , Liang Ngoi Zi , Chen S. H. Annabel 
Published: April 2023

AbstractVisual illusions are a gateway to understand how we construct our experience of reality. Unfortunately, important questions remain open, such as the hypothesis of a common factor underlying the sensitivity to different types of illusions, as well as of personality correlates of illusion sensitivity. In this study, we used a novel parametric framework for visual illusions to generate 10 different classic illusions (Delboeuf, Ebbinghaus, Rod and Frame, Vertical-Horizontal, Zöllner, White, Müller-Lyer, Ponzo, Poggendorff, Contrast) varying in strength, embedded in a perceptual discrimination task. We tested the objective effect of the illusions on errors and response times, and extracted participant-level performance scores (n=250) for each illusion. Our results provide evidence in favour of a general factor underlying the sensitivity to different illusions (labelled Factor i). Moreover, we report a positive link between illusion sensitivity and personality traits such as Agreeableness, Honesty-Humility, and negative relationships with Psychoticism, Antagonism, Disinhibition, and Negative Affect.
CBCT-based synthetic CT generated using CycleGAN with HU correction for adaptive radiotherapy of nasopharyngeal carcinoma
Authors: Jihong Chen , Kerun Quan , Kaiqiang Chen , Xiuchun Zhang , Yimin Zhou , penggang Bai 
Published: April 2023

AbstractThis study aims to utilize a hybrid approach of phantom correction and deep learning for synthesized CT (sCT) images generation based on cone-beam CT (CBCT) images for nasopharyngeal carcinoma (NPC). 52 CBCT/CT paired images of NPC patients were used for model training (41), validation (11). Hounsfield Units (HU) of the CBCT images was calibrated by a commercially available CIRS phantom. Then the original CBCT and the corrected CBCT (CBCT_cor) were trained separately with the same cycle generative adversarial network (CycleGAN) to generate SCT1 and SCT2. The mean error and mean absolute error (MAE) were used to quantify the image quality. For validations, the contours and treatment plans in CT images were transferred to original CBCT, CBCT_cor, SCT1 and SCT2 for dosimetric comparison. Dose distribution, dosimetric parameters and 3D gamma passing rate were analyzed. Compared with rigidly registered CT (RCT), the MAE of CBCT, CBCT_cor, SCT1 and SCT2 were 346.11 ± 13.58 HU, 145.95 ± 17.64 HU, 105.62 ± 16.08 HU and 83.51 ± 7.71 HU, respectively. Moreover, the average dosimetric parameter differences for the CBCT_cor, SCT1 and SCT2 were 2.7% ± 1.4%, 1.2% ± 1.0% and 0.6% ± 0.6%, respectively. Using the dose distribution of RCT images as reference, the 3D gamma passing rate of the hybrid method was significantly better than the other methods. The effectiveness of CBCT-based sCT generated using CycleGAN with HU correction for adaptive radiotherapy of nasopharyngeal carcinoma was confirmed. The image quality and dose accuracy of SCT2 were outperform the simple CycleGAN method. This finding has great significance for the clinical application of adaptive radiotherapy for NPC.
Initial development and testing of an exhaled microRNA detection strategy for lung cancer case–control discrimination
Authors: Shi Miao , Han Weiguo , Loudig Olivier , Shah Chirag D. , Dobkin Jay B. , Keller Steven , Sadoughi Ali , Zhu Changcheng , Siegel Robert E. , Fernandez Maria Katherine , DeLaRosa Lizett , Patel Dhruv , Desai Aditi , Siddiqui Taha , Gombar Saurabh , Suh Yousin , Wang Tao , Hosgood H. Dean , Pradhan Kith , Ye Kenny , Spivack Simon D. 
Published: April 2023

AbstractFor detecting field carcinogenesis non-invasively, early technical development and case–control testing of exhaled breath condensate microRNAs was performed. In design, human lung tissue microRNA-seq discovery was reconciled with TCGA and published tumor-discriminant microRNAs, yielding a panel of 24 upregulated microRNAs. The airway origin of exhaled microRNAs was topographically “fingerprinted”, using paired EBC, upper and lower airway donor sample sets. A clinic-based case–control study (166 NSCLC cases, 185 controls) was interrogated with the microRNA panel by qualitative RT-PCR. Data were analyzed by logistic regression (LR), and by random-forest (RF) models. Feasibility testing of exhaled microRNA detection, including optimized whole EBC extraction, and RT and qualitative PCR method evaluation, was performed. For sensitivity in this low template setting, intercalating dye-based URT-PCR was superior to fluorescent probe-based PCR (TaqMan). In application, adjusted logistic regression models identified exhaled miR-21, 33b, 212 as overall case–control discriminant. RF analysis of combined clinical + microRNA models showed modest added discrimination capacity (1.1–2.5%) beyond clinical models alone: all subjects 1.1% (p = 8.7e−04)); former smokers 2.5% (p = 3.6e−05); early stage 1.2% (p = 9.0e−03), yielding combined ROC AUC ranging from 0.74 to 0.83. We conclude that exhaled microRNAs are qualitatively measureable, reflect in part lower airway signatures; and when further refined/quantitated, can potentially help to improve lung cancer risk assessment.
A comparative analysis of lipoprotein transport proteins: LolA and LolB from Vibrio cholerae and LolA from Porphyromonas gingivalis
Authors: Jaiman Deepika , Nagampalli Raghavendra , Persson Karina 
Published: April 2023

AbstractIn Gram-negative bacteria, N-terminal lipidation is a signal for protein trafficking from the inner membrane (IM) to the outer membrane (OM). The IM complex LolCDE extracts lipoproteins from the membrane and moves them to the chaperone LolA. The LolA-lipoprotein complex crosses the periplasm after which the lipoprotein is anchored to the OM. In γ-proteobacteria anchoring is assisted by the receptor LolB, while a corresponding protein has not been identified in other phyla. In light of the low sequence similarity between Lol-systems from different phyla and that they may use different Lol components, it is crucial to compare representative proteins from several species. Here we present a structure–function study of LolA and LolB from two phyla: LolA from Porphyromonas gingivalis (phylum bacteroidota), and LolA and LolB from Vibrio cholerae (phylum proteobacteria). Despite large sequence differences, the LolA structures are very similar, hence structure and function have been conserved throughout evolution. However, an Arg-Pro motif crucial for function in γ-proteobacteria has no counterpart in bacteroidota. We also show that LolA from both phyla bind the antibiotic polymyxin B whereas LolB does not. Collectively, these studies will facilitate the development of antibiotics as they provide awareness of both differences and similarities across phyla.
Forensic application of epidermal expression of HSP27 and HSP70 for the determination of wound vitality in human compressed neck skin
Authors: Zhang Siying , Ishida Yuko , Ishigami Akiko , Nosaka Mizuho , Kuninaka Yumi , Yasuda Haruki , Kofuna Ayumi , Matsuki Jumpei , Osako Miyu , Zhang Wei , Kimura Akihiko , Furukawa Fukumi , Kondo Toshikazu 
Published: April 2023

AbstractEstimating the age and vitality of human skin wounds is essential in forensic practice, and the use of immunohistochemical parameters in this regard remains a challenge. Heat shock proteins (HSPs) are evolutionarily conserved universal proteins that protect biological systems from various types of stress. However, its importance in forensic pathology for determining wound activation in neck compression skin remains unclear. The expression of HSP27 and HSP70 in neck skin samples was immunohistochemically examined to understand its forensic applicability in determining wound vitality. Skin samples were obtained from 45 cases of neck compression (hanging, 32 cases; strangulation, 10 cases; manual strangulation, 2 cases; other, 1 case) during forensic autopsies; intact skin from the same individual was used as a control. HSP27 expression was detected in 17.4% of keratinocytes in the intact skin samples. In the compressed region, the frequency of HSP27 expression in keratinocytes was 75.8%, which was significantly higher than that in intact skin. Similarly, HSP70 expression was 24.8% in intact skin samples and 81.9% in compressed skin samples, significantly higher in compressed skin than in intact skin samples. This increase in case compression cases may be due to the cell defence role of HSPs. From a forensic pathology perspective, the immunohistochemical examination of HSP27 and HSP70 expression in neck skin could be considered a valuable marker for diagnosing traces of antemortem compression.
Effect of Laminaria digitata dietary inclusion and CAZyme supplementation on blood cells, serum metabolites and hepatic lipids and minerals of weaned piglets
Authors: Ribeiro David M. , Pinto Rui M. A. , Lopes Paula A. , Pestana José M. , Alfaia Cristina M. , Costa Mónica M. , Carvalho Daniela F. P. , Mourato Miguel P. , de Almeida André M. , Freire João P. B. , Prates José A. M. 
Published: April 2023

AbstractSeaweeds, such as Laminaria digitata, are a sustainable alternative to conventional feedstuffs for weaned piglet diets, improving their health and mitigating environmental impacts. L. digitata has a complex cell wall that can be difficult for monogastrics to digest. However, carbohydrate-active enzymes (CAZymes) such as Rovabio® Excel AP and alginate lyase can help break down these polysaccharides and render intracellular nutrients more accessible. This study aimed to evaluate the impact of 10% L. digitata feed inclusion and CAZyme supplementation on piglet blood cells, serum metabolites, liver lipid and mineral profiles. Forty weaned piglets were randomly assigned to one of four diets (n = 10 each): a control diet, 10% L. digitata (LA), 10% L. digitata + 0.005% Rovabio® Excel AP (LAR), and 10% L. digitata + 0.01% alginate lyase (LAL). After two weeks of trial, animals were slaughtered and liver and blood serum samples taken for analysis. The results showed that the LA and LAL diets increased blood lymphocytes, IgG and IgM, and decreased serum lipids, improving both cellular and humoral immune response and cardiovascular health. Dietary CAZymes reversed the anti-inflammatory and hematopoietic effects. Additionally, cortisol levels were reduced with seaweed inclusion compared to the control diet (P < 0.001). In the liver, total n-3 PUFA and n-6/n-3 ratio were increased and decreased, respectively, due to eicosapentaenoic acid and α-linolenic acid accumulation (P < 0.001). However, total liver mineral content was incorporated to a lesser extent with the combined seaweed and enzyme diets (P < 0.001), potentially indicating a negative effect on mineral bioavailability. Overall, results suggest that a 10% L. digitata inclusion can effectively improve piglet health by reducing stress during weaning, without the need for dietary CAZymes.
Identification and pathogenicity analysis of leaf brown spot of Juglans regia in China
Authors: Wang Feihu , Liu Chao , Zeng Qian , Zhou Yijie , Liu Feng , Xu Xiulan , Yang Hanbo , Liu Yinggao , Yang Chunlin 
Published: April 2023

AbstractEnglish walnut (Juglans regia), has high economic and ecological value. As an important tree species for eliminating poverty, it is planted in many Provinces of China. In 2021, new pathogenic fungi were observed in English walnut in Guangyuan City, Sichuan Province, China. The initial symptom of leaf infection is that the leaves are covered with small black spots, which gradually expand into larger brown spots. Most of the spots appeared at the edges of the leaves, and yellow whorls were observed at the junction between the spots and the healthy leaves. The pathogenic fungi were isoalted form collecting disease samples and purified by single-spore culturing. In vitro and field experiments showed that the pathogen could cause brown spots on walnut leaves. The inoculation experiment showed that the symptoms in the field experiment were the same as those observed on the spot; however, slight differences were observed in the in vitro experiment. Ten isolates were obtained from walnut leaves with brown spot symptoms, and these were further characterized based on morphology and DNA sequencing. ITS (internal transcribed spacer), LSU (large sub-unit rDNA), rpb2 (second largest subunit of RNA polymerase) and tub2 (beta-tubulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. The isolate was identified as Nothophoma quercina by morphological and polygene analyses. As far as we are aware, the brown spots on walnut leaves caused by N. quercina is the first report of its kind.
Spatial distribution characteristics of plumes induced by femtosecond laser ablation of silicon in vacuum
Authors: Chen Zhandong , Ning Hua , Zhang Xiulan 
Published: April 2023

AbstractThe spatial distribution characteristics of plumes induced by femtosecond laser ablation of silicon in vacuum are studied by using spectroscopy. The plume spatial distribution clearly shows two zones with different characteristics. The center of the first zone is at a distance of approximately 0.5 mm from the target. Silicon ionic radiation, recombination radiation, and bremsstrahlung mainly occur in this zone, causing an exponential decay with a decay constant of approximately 0.151–0.163 mm. The second zone with a greater area, whose center is at a distance of approximately 1.5 mm from the target, follows the first zone. In this zone, the radiation from silicon atoms and electron-atom collisions dominates, leading to an allometric decay with an allometric exponent of approximately − 1.475 to − 1.376. In the second zone, the electron density spatial distribution is approximately arrowhead-shaped, which is potentially induced by collisions between ambient molecules and the particles in front of the plume. These results indicate that both the recombination effect and expansion effect play important roles and compete with each other in plumes. The recombination effect is dominant near the silicon surface, causing exponential decay. As the distance increases, the electron density decreases exponentially by recombination, causing a more intense expansion effect.