bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camel nanobody-based B7-H3 CAR-T cells show high efficacy against large solid tumours
Authors: Li Dan , Wang Ruixue , Liang Tianyuzhou , Ren Hua , Park Chaelee , Tai Chin-Hsien , Ni Weiming , Zhou Jing , Mackay Sean , Edmondson Elijah , Khan Javed , Croix Brad St , Ho Mitchell 
Published: September 2023

AbstractRational design of chimeric antigen receptor T (CAR-T) cells based on the recognition of antigenic epitopes capable of evoking the most potent CAR activation is an important objective in optimizing immune therapy. In solid tumors, the B7-H3 transmembrane protein is an emerging target that harbours two distinct epitope motifs, IgC and IgV, in its ectodomain. Here, we generate dromedary camel nanobodies targeting B7-H3 and demonstrate that CAR-T cells, based on the nanobodies recognizing the IgC but not IgV domain, had potent antitumour activity against large tumors in female mice. These CAR-T cells are characterized by highly activated T cell signaling and significant tumor infiltration. Single-cell transcriptome RNA sequencing coupled with functional T-cell proteomics analysis uncovers the top-upregulated genes that might be critical for the persistence of polyfunctional CAR-T cells in mice. Our results highlight the importance of the specific target antigen epitope in governing optimal CAR-T activity and provide a nanobody-based B7-H3 CAR-T product for use in solid tumor therapy.
Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding
Authors: Suzuki Shota , Tanaka Kotaro , Nishikawa Kouki , Suzuki Hiroshi , Oshima Atsunori , Fujiyoshi Yoshinori 
Published: September 2023

AbstractHydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms.
Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive Gs signaling
Authors: Nie Yingying , Qiu Zeming , Chen Sijia , Chen Zhao , Song Xiaocui , Ma Yan , Huang Niu , Cyster Jason G. , Zheng Sanduo 
Published: September 2023

AbstractMany orphan G protein-coupled receptors (GPCRs) remain understudied because their endogenous ligands are unknown. Here, we show that a group of class A/rhodopsin-like orphan GPCRs including GPR61, GPR161 and GPR174 increase the cAMP level similarly to fully activated D1 dopamine receptor (D1R). We report cryo-electron microscopy structures of the GPR61‒Gs, GPR161‒Gs and GPR174‒Gs complexes without any exogenous ligands. The GPR174 structure reveals that endogenous lysophosphatidylserine (lysoPS) is copurified. While GPR174 fails to respond to exogenous lysoPS, likely owing to its maximal activation by the endogenous ligand, GPR174 mutants with lower ligand binding affinities can be specifically activated by lysoPS but not other lipids, in a dose-dependent manner. Moreover, GPR174 adopts a non-canonical Gs coupling mode. The structures of GPR161 and GPR61 reveal that the second extracellular loop (ECL2) penetrates into the orthosteric pocket, possibly contributing to constitutive activity. Our work definitively confirms lysoPS as an endogenous GPR174 ligand and suggests that high constitutive activity of some orphan GPCRs could be accounted for by their having naturally abundant ligands.
The gendered effects of the COVID-19 pandemic on adolescent literacy and schooling outcomes in India
Authors: Nandi Arindam , Haberland Nicole , Kozak Meredith , Ngô Thoại D. 
Published: September 2023

AbstractThe COVID-19 pandemic disrupted education delivery around the world, with school closures affecting over 1.6 billion students worldwide. In India, schools were closed for over 18 months, affecting 248 million students. This study estimates the effect of the pandemic on adolescent literacy and schooling outcomes in India. We used data from the National Family Health Survey. (NFHS-5) which covered 636,699 households across all districts of India from June 2019 to April 2021. We considered 15–17 year old adolescents who were surveyed after March 2020 as the post-COVID group while those surveyed earlier were included in the pre-COVID group. We used propensity score matching and inverse propensity score weighted regression methods to account for differences in socioeconomic characteristics between the two groups. Rates of literacy (ability to read a complete sentence) were 1.5–1.6% lower among post-COVID girls as compared with similar pre-COVID girls. Among post-COVID girls in the lowest wealth quintile, rates of literacy were 3.1–3.8% lower than similar pre-COVID girls. There was no loss in literacy among post-COVID girls in the highest wealth quintile. COVID-induced loss in literacy among girls was twice in rural areas as compared to urban areas, and substantially higher among socioeconomically disadvantaged caste groups as compared with privileged caste groups. Post-COVID girls also had 0.08–0.1 lower years of schooling completed than similar pre-COVID girls but there was no difference in out-of-school rates. In a smaller subsample of 15–17 year old boys, the post-COVID group had 2% lower out-of-school rates and there was no difference in literacy or years of schooling completed as compared with matched pre-COVID boys. While markers of vulnerability such as residence, caste, and poverty further amplified the risk of learning. loss for girls, they did not have the same effect on boys.
Peatland restoration increases water storage and attenuates downstream stormflow but does not guarantee an immediate reversal of long-term ecohydrological degradation
Authors: Gatis Naomi , Benaud Pia , Anderson Karen , Ashe Josie , Grand-Clement Emilie , Luscombe David J. , Puttock Alan , Brazier Richard E. 
Published: September 2023

AbstractPeatland restoration is experiencing a global upsurge as a tool to protect and provide various ecosystem services. As the range of peatland types being restored diversifies, do previous findings present overly optimistic restoration expectations? In an eroding and restored upland peatland we assessed short-term (0–4 year) effects of restoration on ecohydrological functions. Restoration significantly reduced discharge from the site, transforming peat pans into pools. These retained surface water over half the time and were deeper during wet periods than before. In the surrounding haggs water tables stabilised, as drawdown during dry conditions reduced, increasing the saturated peat thickness. Despite these changes, there were no effects on photosynthesis, ecosystem respiration or dissolved organic carbon loads leaving the site. Soil respiration did not decrease as water tables rose, but methane emissions were higher from rewet pools. Restoration has had a dramatic effect on hydrology, however, consequent changes in other ecosystem functions were not measured in the 4 years after restoration. Whilst restoration is crucial in halting the expansion of degraded peatland areas, it is vital that practitioners and policymakers advocating for restoration are realistic about the expected outcomes and timescales over which these outcomes may manifest.
A machine learning approach to seizure detection in a rat model of post-traumatic epilepsy
Authors: Kotloski Robert J. 
Published: September 2023

AbstractEpilepsy is a common neurologic condition frequently investigated using rodent models, with seizures identified by electroencephalography (EEG). Given technological advances, large datasets of EEG are widespread and amenable to machine learning approaches for identification of seizures. While such approaches have been explored for human EEGs, machine learning approaches to identifying seizures in rodent EEG are limited. We utilized a predesigned deep convolutional neural network (DCNN), GoogLeNet, to classify images for seizure identification. Training images were generated through multiplexing spectral content (scalograms), kurtosis, and entropy for two-second EEG segments. Over 2200 h of EEG data were scored for the presence of seizures, with 95.6% of seizures identified by the DCNN and a false positive rate of 34.2% (1.52/h), as compared to visual scoring. Multiplexed images were superior to scalograms alone (scalogram-kurtosis-entropy 0.956 ± 0.010, scalogram 0.890 ± 0.028, t(7) = 3.54, p < 0.01) and a DCNN trained specifically for the individual animal was superior to using DCNNs across animals (intra-animal 0.960 ± 0.0094, inter-animal 0.811 ± 0.015, t(30) = 5.54, p < 0.01). For this dataset the DCNN approach is superior to a previously described algorithm utilizing longer local line lengths, calculated from wavelet-decomposition of EEG, to identify seizures. We demonstrate the novel use of a predesigned DCNN constructed to classify images, utilizing multiplexed images of EEG spectral content, kurtosis, and entropy, to rapidly and objectively identifies seizures in a large dataset of rat EEG with high sensitivity.
Improved corrosion resistance of permanganate-phosphate conversion coat on steel surface by surfactants
Authors: Abd-El-Nabey B. A. , El-Housseiny S. , Abd-El-Fatah M. A. 
Published: September 2023

AbstractIn the present work, we studied the effect of the presence of different concentrations of each of Triton-X-100 and Tween-80 surfactants in the bath of permanganate-phosphate conversion coating (PPC) on the corrosion resistance and the microstructure of the prepared coats. The coats were investigated using a scanning electron microscope (SEM), an energy dispersive X-ray spectrometer (EDX), X-ray photoelectron spectroscopy (XPS), electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization techniques. The SEM results show that, on addition of the surfactants to the PPC bath, the porosity of the coat decreases and the coating layer becomes more compact. EIS results indicated that the presence of 0.01 M Triton-X-100 or 0.01 M Tween-80 in the coating solution caused an increase in the protection efficiency of the coat up to 93.7% and 84.1%, respectively. The potentiodynamic polarization results indicated that the two surfactants mainly act as anodic inhibitors due to the adsorption of their molecules at the anodic sites of the surface of steel and retard its oxidation reaction. The EDX and XPS results confirmed the results of the other techniques. A mechanism for the role of the surfactants in the coating process was proposed using the results of XPS and the other techniques.
Geographic destiny trumps taxonomy in the Roundtail Chub, Gila robusta species complex (Teleostei, Leuciscidae)
Authors: Suchocki Christopher R. , Ka‘apu-Lyons Cassie , Copus Joshua M. , Walsh Cameron A. J. , Lee Anne M. , Carter Julie Meka , Johnson Eric A. , Etter Paul D. , Forsman Zac H. , Bowen Brian W. , Toonen Robert J. 
Published: September 2023

AbstractThe Gila robusta species complex in the lower reaches of the Colorado River includes three nominal and contested species (G. robusta, G. intermedia, and G. nigra) originally defined by morphological and meristic characters. In subsequent investigations, none of these characters proved diagnostic, and species assignments were based on capture location. Two recent studies applied conservation genomics to assess species boundaries and reached contrasting conclusions: an ezRAD phylogenetic study resolved 5 lineages with poor alignment to species categories and proposed a single species with multiple population partitions. In contrast, a dd-RAD coalescent study concluded that the three nominal species are well-supported evolutionarily lineages. Here we developed a draft genome (~ 1.229 Gbp) to apply genome-wide coverage (10,246 SNPs) with nearly range-wide sampling of specimens (G. robusta N = 266, G. intermedia N = 241, and G. nigra N = 117) to resolve this debate. All three nominal species were polyphyletic, whereas 5 of 8 watersheds were monophyletic. AMOVA partitioned 23.1% of genetic variance among nominal species, 30.9% among watersheds, and the Little Colorado River was highly distinct (FST ranged from 0.79 to 0.88 across analyses). Likewise, DAPC identified watersheds as more distinct than species, with the Little Colorado River having 297 fixed nucleotide differences compared to zero fixed differences among the three nominal species. In every analysis, geography explains more of the observed variance than putative taxonomy, and there are no diagnostic molecular or morphological characters to justify species designation. Our analysis reconciles previous work by showing that species identities based on type location are supported by significant divergence, but natural geographic partitions show consistently greater divergence. Thus, our data confirm Gila robusta as a single polytypic species with roughly a dozen highly isolated geographic populations, providing a strong scientific basis for watershed-based future conservation.
Comparative proteomic analysis of edible bird’s nest from different origins
Authors: Wang Xianyang , Hu Dingwen , Liao Feng , Chen Sitai , Meng Yu , Dai Jie , Dong Tina Ting Xia , Lao Zizhao , Yu Liangwen , Liang Yueliang , Lai Xiaoping , Tsim Karl Wah Keung , Li Geng 
Published: September 2023

AbstractEdible bird’s nest (EBN) mainly made of saliva that secreted by a variety of swiftlets is a kind of precious traditional Chinese medicine. EBNs from different biological and geographical origins exhibit varieties in morphology, material composition, nutritive value and commercial value. Here, we collected four different EBN samples from Huaiji, China (Grass EBN), Nha Trang, Vietnam (Imperial EBN) and East Kalimantan, Indonesia (White EBN and Feather EBN) respectively, and applied label-free quantitative MS-based proteomics technique to identify its protein composition. First, phylogenetic analysis was performed based on cytb gene to identify its biological origin. Second, a total of 37 proteins of EBNs were identified, among which there were six common proteins that detected in all samples and exhibited relatively higher content. Gene ontology analysis revealed the possible function of EBN proteins, and principal component analysis and hierarchical clustering analysis based on 37 proteins were performed to compare the difference of various EBNs. In summary, our study deciphered the common and characteristic protein components of EBNs of different origins and described their possible functions by GO enrichment analysis, which helps to establish an objective and reliable quality evaluation system.
Unveiling metabolic pathways involved in the extreme desiccation tolerance of an Atacama cyanobacterium
Authors: Moore Rachel A. , Azua-Bustos Armando , González-Silva Carlos , Carr Christopher E. 
Published: September 2023

AbstractGloeocapsopsis dulcis strain AAB1 is an extremely xerotolerant cyanobacterium isolated from the Atacama Desert (i.e., the driest and oldest desert on Earth) that holds astrobiological significance due to its ability to biosynthesize compatible solutes at ultra-low water activities. We sequenced and assembled the G. dulcis genome de novo using a combination of long- and short-read sequencing, which resulted in high-quality consensus sequences of the chromosome and two plasmids. We leveraged the G. dulcis genome to generate a genome-scale metabolic model (iGd895) to simulate growth in silico. iGd895 represents, to our knowledge, the first genome-scale metabolic reconstruction developed for an extremely xerotolerant cyanobacterium. The model's predictive capability was assessed by comparing the in silico growth rate with in vitro growth rates of G. dulcis, in addition to the synthesis of trehalose. iGd895 allowed us to explore simulations of key metabolic processes such as essential pathways for water-stress tolerance, and significant alterations to reaction flux distribution and metabolic network reorganization resulting from water limitation. Our study provides insights into the potential metabolic strategies employed by G. dulcis, emphasizing the crucial roles of compatible solutes, metabolic water, energy conservation, and the precise regulation of reaction rates in their adaptation to water stress.
Association between weight loss agents and elevated liver enzymes: a population-based cross-sectional study
Authors: Kim Ye-Jee , Kang Seo Young , Kim Mi-Sook , Lee Joongyub , Yang Bo Ram 
Published: September 2023

AbstractThe widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08–1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12–1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03–1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93–3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14–3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02–1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed.
Optical and spin-selective time-of-flight measurement of light-induced desorption of Rb from Fe$$_3$$O$$_4$$ surfaces
Authors: Asakawa Kanta , Tanabe Naoki , Kawauchi Taizo , Fukutani Katsuyuki , Hatakeyama Atsushi 
Published: September 2023

AbstractLight-induced desorption of Rb atoms from a ferrimagnetic Fe$$_3$$

3

O$$_4$$

4

(001) surface was studied using a spin-selective optical method, which provides information on the spin polarization, velocity distribution, and amount of the desorbed atoms. The results showed that the intensity of the desorption of Rb from Fe$$_3$$

3

O$$_4$$

4

(001) induced by ultraviolet (UV) light irradiation was smaller than the detection limit at coverages lower than the threshold coverage at which the desorption rate began to increase. Moreover, the average magnetic quantum number of the desorbed atoms was smaller than that of electrons at the Fermi level of the Fe$$_3$$

3

O$$_4$$

4

(001) surface. These indicate that the light-induced desorption of Rb from an Fe$$_3$$

3

O$$_4$$

4

(001) surface occurs only in the high-coverage region in which the desorbing atoms are not in contact with the Fe$$_3$$

3

O$$_4$$

4

surface, and that the desorption does not involve spin transfer.
The Coral Triangle and Strait of Malacca are two distinct hotspots of mangrove biodiversity
Authors: Goulding Tricia C. , Dayrat Benoît 
Published: September 2023

AbstractKnowledge of the biogeography of marine taxa has lagged significantly behind terrestrial ecosystems. A hotspot of marine biodiversity associated with coral reefs is known in the Coral Triangle of the Indo-West Pacific, but until now there was little data with which to evaluate broad patterns of species richness in the coastal fauna of ecosystems other than coral reefs. This data is critically needed for fauna with low functional redundancy like that of mangroves, that are vulnerable to habitat loss and rising sea levels. Here we show that the diversity of mangrove fauna is characterized by two distinct hotspots in the Indo-West Pacific, associated with two habitat types: fringe mangroves in the Coral Triangle, and riverine mangroves in the Strait of Malacca, between the west coast of Peninsular Malaysia and Sumatra. This finding, based on a family of slugs of which the systematics has been completely revised, illustrates an unexpected biogeographic pattern that emerged only after this taxon was studied intensively. Most organisms that live in the mangrove forests of Southeast Asia remain poorly known both taxonomically and ecologically, and the hotspot of diversity of onchidiid slugs in the riverine mangroves of the Strait of Malacca indicates that further biodiversity studies are needed to support effective conservation of mangrove biodiversity.
The relation between implicit statistical learning and proactivity as revealed by EEG
Authors: Sznabel Dorota , Land Rüdiger , Kopp Bruno , Kral Andrej 
Published: September 2023

AbstractEnvironmental events often occur on a probabilistic basis but can sometimes be predicted based on specific cues and thus approached proactively. Incidental statistical learning enables the acquisition of knowledge about probabilistic cue-target contingencies. However, the neural mechanisms of statistical learning about contingencies (SLC), the required conditions for successful learning, and the role of implicit processes in the resultant proactive behavior are still debated. We examined changes in behavior and cortical activity during an SLC task in which subjects responded to visual targets. Unbeknown to them, there were three types of target cues associated with high-, low-, and zero target probabilities. About half of the subjects spontaneously gained explicit knowledge about the contingencies (contingency-aware group), and only they showed evidence of proactivity: shortened response times to predictable targets and enhanced event-related brain responses (cue-evoked P300 and contingent negative variation, CNV) to high probability cues. The behavioral and brain responses were strictly associated on a single-trial basis. Source reconstruction of the brain responses revealed activation of fronto-parietal brain regions associated with cognitive control, particularly the anterior cingulate cortex and precuneus. We also found neural correlates of SLC in the contingency-unaware group, but these were restricted to post-target latencies and visual association areas. Our results document a qualitative difference between explicit and implicit learning processes and suggest that in certain conditions, proactivity may require explicit knowledge about contingencies.