bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local structural preferences in shaping tau amyloid polymorphism
Authors: Louros Nikolaos , Wilkinson Martin , Tsaka Grigoria , Ramakers Meine , Morelli Chiara , Garcia Teresa , Gallardo Rodrigo , D’Haeyer Sam , Goossens Vera , Audenaert Dominique , Thal Dietmar Rudolf , Mackenzie Ian R. , Rademakers Rosa , Ranson Neil A. , Radford Sheena E. , Rousseau Frederic , Schymkowitz Joost 
Published: February 2024

AbstractTauopathies encompass a group of neurodegenerative disorders characterised by diverse tau amyloid fibril structures. The persistence of polymorphism across tauopathies suggests that distinct pathological conditions dictate the adopted polymorph for each disease. However, the extent to which intrinsic structural tendencies of tau amyloid cores contribute to fibril polymorphism remains uncertain. Using a combination of experimental approaches, we here identify a new amyloidogenic motif, PAM4 (Polymorphic Amyloid Motif of Repeat 4), as a significant contributor to tau polymorphism. Calculation of per-residue contributions to the stability of the fibril cores of different pathologic tau structures suggests that PAM4 plays a central role in preserving structural integrity across amyloid polymorphs. Consistent with this, cryo-EM structural analysis of fibrils formed from a synthetic PAM4 peptide shows that the sequence adopts alternative structures that closely correspond to distinct disease-associated tau strains. Furthermore, in-cell experiments revealed that PAM4 deletion hampers the cellular seeding efficiency of tau aggregates extracted from Alzheimer’s disease, corticobasal degeneration, and progressive supranuclear palsy patients, underscoring PAM4’s pivotal role in these tauopathies. Together, our results highlight the importance of the intrinsic structural propensity of amyloid core segments to determine the structure of tau in cells, and in propagating amyloid structures in disease.
Geometric transformation adaptive optics (GTAO) for volumetric deep brain imaging through gradient-index lenses
Authors: Li Yuting , Cheng Zongyue , Wang Chenmao , Lin Jianian , Jiang Hehai , Cui Meng 
Published: February 2024

AbstractThe advance of genetic function indicators has enabled the observation of neuronal activities at single-cell resolutions. A major challenge for the applications on mammalian brains is the limited optical access depth. Currently, the method of choice to access deep brain structures is to insert miniature optical components. Among these validated miniature optics, the gradient-index (GRIN) lens has been widely employed for its compactness and simplicity. However, due to strong fourth-order astigmatism, GRIN lenses suffer from a small imaging field of view, which severely limits the measurement throughput and success rate. To overcome these challenges, we developed geometric transformation adaptive optics (GTAO), which enables adaptable achromatic large-volume correction through GRIN lenses. We demonstrate its major advances through in vivo structural and functional imaging of mouse brains. The results suggest that GTAO can serve as a versatile solution to enable large-volume recording of deep brain structures and activities through GRIN lenses.
Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice
Authors: Zhang Fengwei , Qiao Wei , Wei Ji-an , Tao Zhengyi , Chen Congjia , Wu Yefeng , Lin Minghui , Ng Ka Man Carmen , Zhang Li , Yeung Kelvin Wai-Kwok , Chow Billy Kwok Chong 
Published: February 2024

AbstractSecretin, though originally discovered as a gut-derived hormone, is recently found to be abundantly expressed in the ventromedial hypothalamus, from which the central neural system controls satiety, energy metabolism, and bone homeostasis. However, the functional significance of secretin in the ventromedial hypothalamus remains unclear. Here we show that the loss of ventromedial hypothalamus-derived secretin leads to osteopenia in male and female mice, which is primarily induced by diminished cAMP response element-binding protein phosphorylation and upregulation in peripheral sympathetic activity. Moreover, the ventromedial hypothalamus-secretin inhibition also contributes to hyperphagia, dysregulated lipogenesis, and impaired thermogenesis, resulting in obesity in male and female mice. Conversely, overexpression of secretin in the ventromedial hypothalamus promotes bone mass accrual in mice of both sexes. Collectively, our findings identify an unappreciated secretin signaling in the central neural system for the regulation of energy and bone metabolism, which may serve as a new target for the clinical management of obesity and osteoporosis.
Phosphoglycerate kinase 1 acts as a cargo adaptor to promote EGFR transport to the lysosome
Authors: Chu Shao-Ling , Huang Jia-Rong , Chang Yu-Tzu , Yao Shu-Yun , Yang Jia-Shu , Hsu Victor W. , Hsu Jia-Wei 
Published: February 2024

AbstractThe epidermal growth factor receptor (EGFR) plays important roles in multiple cellular events, including growth, differentiation, and motility. A major mechanism of downregulating EGFR function involves its endocytic transport to the lysosome. Sorting of proteins into intracellular pathways involves cargo adaptors recognizing sorting signals on cargo proteins. A dileucine-based sorting signal has been identified previously for the sorting of endosomal EGFR to the lysosome, but a cargo adaptor that recognizes this signal remains unknown. Here, we find that phosphoglycerate kinase 1 (PGK1) is recruited to endosomal membrane upon its phosphorylation, where it binds to the dileucine sorting signal in EGFR to promote the lysosomal transport of this receptor. We also elucidate two mechanisms that act in concert to promote PGK1 recruitment to endosomal membrane, a lipid-based mechanism that involves phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and a protein-based mechanism that involves hepatocyte growth factor receptor substrate (Hrs). These findings reveal an unexpected function for a metabolic enzyme and advance the mechanistic understanding of how EGFR is transported to the lysosome.
Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis
Authors: Guo Xuanming , Asthana Pallavi , Zhai Lixiang , Cheng Ka Wing , Gurung Susma , Huang Jiangang , Wu Jiayan , Zhang Yijing , Mahato Arun Kumar , Saarma Mart , Ustav Mart , Kwan Hiu Yee , Lyu Aiping , Chan Kui Ming , Xu Pingyi , Bian Zhao-Xiang , Wong Hoi Leong Xavier 
Published: February 2024

AbstractObesity, a global health challenge, is a major risk factor for multiple life-threatening diseases, including diabetes, fatty liver, and cancer. There is an ongoing need to identify safe and tolerable therapeutics for obesity management. Herein, we show that treatment with artesunate, an artemisinin derivative approved by the FDA for the treatment of severe malaria, effectively reduces body weight and improves metabolic profiles in preclinical models of obesity, including male mice with overnutrition-induced obesity and male cynomolgus macaques with spontaneous obesity, without inducing nausea and malaise. Artesunate promotes weight loss and reduces food intake in obese mice and cynomolgus macaques by increasing circulating levels of Growth Differentiation Factor 15 (GDF15), an appetite-regulating hormone with a brainstem-restricted receptor, the GDNF family receptor α-like (GFRAL). Mechanistically, artesunate induces the expression of GDF15 in multiple organs, especially the liver, in mice through a C/EBP homologous protein (CHOP)-directed integrated stress response. Inhibition of GDF15/GFRAL signalling by genetic ablation of GFRAL or tissue-specific knockdown of GDF15 abrogates the anti-obesity effect of artesunate in mice with diet-induced obesity, suggesting that artesunate controls bodyweight and appetite in a GDF15/GFRAL signalling-dependent manner. These data highlight the therapeutic benefits of artesunate in the treatment of obesity and related comorbidities.
East Antarctic warming forced by ice loss during the Last Interglacial
Authors: Hutchinson David K. , Menviel Laurie , Meissner Katrin J. , Hogg Andrew McC. 
Published: February 2024

AbstractDuring the Last Interglacial (LIG; 129-116 thousand years before present), the Antarctic ice sheet (AIS) was 1 to 7 m sea level equivalent smaller than at pre-industrial. Here, we assess the climatic impact of partial AIS melting at the LIG by forcing a coupled climate model with a smaller AIS and the equivalent meltwater input around the Antarctic coast. We find that changes in surface elevation induce surface warming over East Antarctica of 2 to 4 °C, and sea surface temperature (SST) increases in the Weddell and Ross Seas by up to 2 °C. Meltwater forcing causes a high latitude SST decrease and a subsurface (100–500 m) ocean temperature increase by up to 2 °C in the Ross Sea. Our results suggest that the combination of a smaller AIS and enhanced meltwater input leads to a larger sub-surface warming than meltwater alone and induces further Antarctic warming than each perturbation separately.
Possible chiral spin liquid state in the S = 1/2 kagome Heisenberg model
Authors: Sun Rong-Yang , Jin Hui-Ke , Tu Hong-Hao , Zhou Yi 
Published: February 2024

AbstractThe nature of the ground state for the S = 1/2 Kagome Heisenberg antiferromagnet (KHAF) has been elusive. We revisit this challenging problem and provide numerical evidence that its ground state is a chiral spin liquid. Combining the density matrix renormalization group method with analytical analyses, we demonstrate that the previously observed chiral spin liquid phase in the KHAF with longer-range couplings is stable in a broader region of the phase diagram. We characterize the nature of the ground state by computing energy derivatives, revealing the ground-state degeneracy arising from the spontaneous breaking of the time-reversal symmetry, and targeting the semion sector. We further investigate the phase diagram in the vicinity of the KHAF and observe a $$\sqrt{3}\times \sqrt{3}$$

3

×

3

magnetically ordered phase and two valence-bond crystal phases.
The neutrophil-to-Lymphocyte ratio is associated with clinical symptoms in first-episode medication-naïve patients with schizophrenia
Authors: Wang Xuan , Chen Xiaofang , Guan Xiaoni , Li Zezhi 
Published: February 2024

AbstractInnate immunity has been shown to be associated with schizophrenia (Sch). This study explored the relationship between symptoms and neutrophil-to-lymphocyte ratio (NLR) (a marker of innate immunity) in patients with Sch. Ninety-seven first-episode medication-naïve (FEMN) patients with Sch and 65 healthy controls were recruited in this study. We measured the complete blood count and assessed the clinical symptoms using the PANSS scales. We found higher NEU counts and NLR in patients with Sch compared with control subjects. Male patients showed a higher NEU count than female patients. In addition, FEMN patients with higher NLR and NEU values showed higher PANSS-p, PANSS-g, and PANSS-total scores (all p < 0.05). Regression analysis revealed that NLR was a predictor for PANSS total scores in patients with Sch. Higher NLR value was observed in patients with Sch and the significant associations between NLR and psychotic symptoms indicate that an imbalance in inflammation and innate immune system may be involved in the pathophysiology of Sch.
Effects of gelatin type and concentration on the preparation and properties of freeze-dried fish oil powders
Authors: Yang Mengyang , Peng Jiawei , Shi Cuiping , Zi Ye , Zheng Yulu , Wang Xichang , Zhong Jian 
Published: February 2024

AbstractThe effects of gelatin type (porcine skin gelatin, PSG; bovine skin gelatin, BSG; fish gelatin, FG; or cold-water fish skin gelatin, CFG) and concentration on the preparation and properties of fish oil powders were investigated in this work. The oil powders were prepared using the combination method of gelatin-sodium hexametaphosphate complex coacervation with starch sodium octenyl succinate (SSOS)-aided freeze-drying. Compared with the other gelatins, CFG—with an unobvious isoelectric point, a lower molecular weight, more hydrogen bonds, and longer gel formation time—could not form complex coacervates, which are necessary to prepare oil powders. For oil powders obtained from the other gelatins, gelatin type and concentration did not have obvious effects on microscale morphologies; they did, however, have significant effects on physicochemical properties. The highest peroxide values of the oil powders were mainly dependent on the gelatins, expressed in the following manner: PSG (153 ± 5 – 168 ± 3 meq/Kg oil) < BSG (176 ± 5 – 188 ± 1 meq/Kg oil) < FG (196 ± 11 – 201 ± 22 meq/Kg oil). Acidic and neutral pH could not dissolve the complex coacervates. However, the oil powders could be quickly dissolved to form emulsion droplets in the gastric phase, and that SSOS increased coacervate stability and promoted oil digestion during the in vitro gastrointestinal process. In sum, this study contributes fundamental information to understanding the development of fish oil solid encapsulation preparations.
A therapeutic hepatitis B mRNA vaccine with strong immunogenicity and persistent virological suppression
Authors: Zhao Huajun , Shao Xianyu , Yu Yating , Huang Lulu , Amor Narh Philip , Guo Kun , Weng Changzhen , Zhao Weijun , Yang Ailu , Hu Jiesen , Yang Hongbao , Liu Zhenguang , Han Qiuju , Shi Leilei , Sun Shiyu , Zhang Jian , Lin Ang , Yang Yong 
Published: February 2024

AbstractHere we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.3), this vaccine demonstrates sufficient and persistent virological suppression, and robust immunogenicity in terms of induction of strong innate immune activation, high-level virus-specific antibodies, memory B cells and T cells. mRNA platform therefore holds prospects for therapeutic vaccine development to combat CHB.
Phytoplankton optical fingerprint libraries for development of phytoplankton ocean color satellite products
Authors: Lomas Michael W. , Neeley Aimee R. , Vandermeulen Ryan , Mannino Antonio , Thomas Crystal , Novak Michael G. , Freeman Scott A. 
Published: February 2024

AbstractPhytoplankton respond to physical and hydrographic forcing on time and space scales up to and including those relevant to climate change. Quantifying changes in phytoplankton communities over these scales is essential for predicting ocean food resources, occurrences of harmful algal blooms, and carbon and other elemental cycles, among other predictions. However, one of the best tools for quantifying phytoplankton communities across relevant time and space scales, ocean color sensors, is constrained by its own spectral capabilities and availability of adequately vetted and relevant optical models. To address this later shortcoming, greater than fifty strains of phytoplankton, from a range of taxonomic lineages, geographic locations, and time in culture, alone and in mixtures, were grown to exponential and/or stationary phase for determination of hyperspectral UV-VIS absorption coefficients, multi-angle and multi-spectral backscatter coefficients, volume scattering functions, particle size distributions, pigment content, and fluorescence. The aim of this publication is to share these measurements to expedite their utilization in the development of new optical models for the next generation of ocean color satellites.
Two chromosome-level genomes of Smittia aterrima and Smittia pratorum (Diptera, Chironomidae)
Authors: Fu Yue , Fang Xiangliang , Xiao Yunli , Mao Bin , Xu Zigang , Shen Mi , Wang Xinhua 
Published: February 2024

AbstractChironomids are one of the most abundant aquatic insects and are widely distributed in various biological communities. However, the lack of high-quality genomes has hindered our ability to study the evolution and ecology of this group. Here, we used Nanopore long reads and Hi-C data to produce two chromosome-level genomes from mixed genomic data. The genomes of Smittia aterrima (SateA) and Smittia pratorum (SateB) were assembled into three chromosomes, with sizes of 78.45 Mb and 71.56 Mb, scaffold N50 lengths of 25.73 and 23.53 Mb, and BUSCO completeness of 98.5% and 97.8% (n = 1,367), 5.68 Mb (7.24%) and 1.94 Mb (2.72%) of repetitive elements, and predicted 12,330 (97.70% BUSCO completeness) and 11,250 (97.40%) protein-coding genes, respectively. These high-quality genomes will serve as valuable resources for comprehending the evolution and environmental adaptation of chironomids.
Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs
Authors: Enomoto Masataka , de Castro Nicholas , Hash Jonathan , Thomson Andrea , Nakanishi-Hester Aoi , Perry Erin , Aker Savannah , Haupt Emily , Opperman Logan , Roe Simon , Cole Tracey , Thompson Nichola Archer , Innes J. F. , Lascelles B. Duncan X. 
Published: February 2024

AbstractThis study aimed to determine the prevalence of osteoarthritis (OA) and associated clinical signs in young dogs. Owners of dogs aged 8 months–4 years from a single practice, were contacted in random order, to participate in a general health screen. Clinical and orthopedic examinations were performed. Each joint was scored for pain reactions (0–4). Orthogonal radiographs of all joints were made under sedation. Each joint was scored for radiographic OA (rOA) severity on an 11-point scale. Clinical OA (cOA) was defined as an overlap of rOA and joint pain in ≥ 1 joint. Owners completed OA questionnaires. The owners of 123 dogs agreed to participate. Overall, 39.8% (49/123) of dogs had rOA in ≥ 1 joint, and 16.3% (20/123) or 23.6% (29/123) dogs had cOA, depending on the cut-off value of joint pain; moderate (2), or mild (1), respectively. Owners of dogs with cOA observed signs of impairment in approximately 30% of cases. Only 2 dogs with cOA were receiving OA pain management. The most commonly affected joints in descending order of frequency were elbow, hip, tarsus, and stifle. Radiographically visible OA is common in young dogs, and 40–60% of dogs with rOA had cOA. However, OA-pain appears underdiagnosed and undertreated in young dogs.
Uncovering floral composition of paper wasp nests (Hymenoptera: Vespidae: Polistes) through DNA metabarcoding
Authors: Mohamadzade Namin Saeed , Son Minwoong , Jung Chuleui 
Published: February 2024

AbstractAs the social organism, Polistes wasps build a communal nest using woody fibers with saliva for sustaining brood and adult population throughout the season. Limited information exists regarding the identification specific plant materials employed in wasp nest building. Thus, we firstly tested if the DNA metabarcoding approach utilizing rbcL and trnL molecular markers could identify the plant species quantitatively and qualitatively inform the mixed-origin woody samples. A threshold of 0.01 proportion of reads was applied for rbcL and trnL molecular markers, while this threshold for median proportion was 0.0025. In assessing taxa richness, the median proportion demonstrated superior performance, exhibiting higher taxa detection power, however, rbcL marker outperformed in quantitative analysis. Subsequently, we applied DNA metabarcoding to identify the plant materials from the nests of two Polistes species, P. mandarinus and P. rothneyi. The results showed that higher preference of Quercus and Robinia as the major nest building materials regardless of the surrounding plant communities, by two wasp species. Material diversity was higher for P. rothneyi than P. mandarinus, which may explain the abundance of this species possibly with heightened adaptive capacities in their nesting behavior. This study demonstrated that DNA metabarcoding could identify the complex nest-building plant materials of paper wasps and provide insights into their ecological interactions in the natural ecosystem.
Vibrations and energy distribution in inhomogeneous rods with elastic and viscous boundary conditions
Authors: Lelkes János , Bak Bendegúz Dezső , Kalmár-Nagy Tamás 
Published: February 2024

AbstractFunctionally graded materials have broad engineering applications including mechanical engineering, electronics, chemistry, and biomedical engineering. One notable advantage of such materials is that their stiffness distribution can be optimized to avoid stress concentration. A novel approach for solving the equations describing the longitudinal vibration of functionally graded rods with viscous and elastic boundary conditions is proposed. The characteristic equation of the system is derived for the solution of the undamped case for the constant stiffness rod. Then, a homotopy method is applied to compute the eigenvalues and mode shapes of graded rods for viscoelastic boundary conditions. The changes of the eigenvalues and mode shapes as function of the damping parameters are investigated. The optimal damping of the system is computed. It is shown that the qualitative behavior depends on the relation between the actual damping and the optimal damping of the system. The energy density distribution of graded rods is also discussed. An energy measure, the mean scaled energy density distribution is introduced to characterize the energy distribution along the rod in the asymptotic time limit. The significance of such a measure is that it reveals how the energy tends to distribute along the rod. It is shown that the energy distribution can be manipulated by changing the damping parameters. Qualitative changes depending on the relation between the actual damping and the optimal damping are highlighted.
Particle flow numerical simulation model for coal and gas outburst and its microscopic outburst mechanism description
Authors: Jiao Huice , Song Weihua 
Published: February 2024

AbstractThe finite difference model and particle flow model were constructed to reproduce the process of coal and gas outburst in front of the tunnel. The reliability of the particle flow model was verified by studying the internal stress, gas pressure, and related parameters of gas and coal two-phase flow. Then the process of coal and gas outburst is described from a microscopic perspective. The results show that the particle flow numerical model of coal and gas outburst is in line with reality and can intuitively and conveniently monitor relevant parameters; The concentrated stress caused by excavation of tunnels can reach 1.2 times the in-situ stress; High stress causes the adhesion between coal particles to break down, which is the main reason for the initiation of coal and gas outbursts; The intermittent breakthrough of gas on the coal particle collection that blocks the release channel has caused pulsating characteristics of coal and gas outbursts.